Prevalence and Clinicopathological Significance of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Retrospective Cohort Study from Kerala, India

Prevalence and Clinicopathological Significance of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Retrospective Cohort Study from Kerala, India | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prevalence and Clinicopathological Significance of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Retrospective Cohort Study from Kerala, India Santhosh Thekkoot Vijayan, Nisha Mohandas, Jithin Joshy Kattuparambil, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8315000/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 22 You are reading this latest preprint version Abstract Background: The BRAF V600E mutation is the most frequent genetic alteration in papillary thyroid carcinoma (PTC) and has been implicated in aggressive tumor behaviour. Its prevalence, however, varies across populations. This study aimed to determine the prevalence of BRAF V600E mutation in a South Indian PTC cohort and to evaluate its association with clinicopathological features. Methods: Tumor specimens from 69 patients with histologically confirmed PTC were subjected to immunohistochemical analysis for BRAF V600E expression. Staining intensity was graded from 0 to 3, with scores > 0 defined as positive. Age distribution across score categories was assessed using one-way ANOVA. Associations between BRAF status and clinicopathological variables—including gender, multifocality, tumor stage, nodal status, metastasis, lymphovascular/perineural invasion (LVI/PNI), and capsular invasion—were analyzed using Chi-square or Fisher’s exact tests. Statistical significance was set at p < 0.05. Results: BRAF V600E positivity was detected in 66.7% (46/69) of cases, with 43.5% of positive tumors demonstrating strong expression (score 3). Among the evaluated parameters, only LVI/PNI showed a significant association with BRAF positivity (p = 0.047; OR 3.34; 95% CI 0.98–11.41). No significant associations were observed between BRAF status and age, gender, T stage, N stage, or distant metastasis. Conclusion: This cohort demonstrated a high prevalence of BRAF V600E mutation in PTC. Its significant association with LVI/PNI suggests a potential link with invasive tumor behaviour. Although limited by sample size and retrospective design, these findings support further prospective research to clarify the prognostic utility of BRAF V600E and its relevance in risk stratification and targeted therapy in PTC. BRAF V600E papillary thyroid carcinoma immunohistochemistry clinicopathological factors lymphovascular invasion Figures Figure 1 Introduction Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy worldwide, accounting for approximately 75–85% of all thyroid cancers.¹Although PTC is associated with an excellent prognosis, with a 10-year survival rate exceeding 90%,¹ a subset of tumors demonstrates aggressive behaviour, including extrathyroidal extension, lymph node metastasis, and reduced sensitivity to radioiodine therapy, which may adversely affect long-term outcomes. 2,3 Recent advances in molecular oncology have identified several genetic alterations involved in thyroid tumorigenesis, particularly within the mitogen-activated protein kinase (MAPK) signalling pathway. 4 Among these, the BRAF V600E mutation is the most prevalent, reported in 45–80% of PTC cases, with notable geographic variation. 5,6 The BRAF gene encodes a serine–threonine kinase that regulates follicular cell growth and differentiation. A valine-to-glutamic acid substitution at codon 600 (V600E) results in constitutive activation of the MAPK pathway, leading to uncontrolled cellular proliferation. 7 Numerous studies have examined the clinicopathological significance of the BRAF V600E mutation in PTC. Most have reported associations with adverse features such as extrathyroidal extension, lymph node metastasis, advanced tumor stage, and increased recurrence risk. 8,9,10 However, other studies have not demonstrated such associations, suggesting that the prognostic impact of BRAF V600E may be influenced by additional genetic, environmental, or epigenetic factors. 11,12 The prevalence of BRAF V600E shows considerable regional variation, with higher rates reported in Asian populations (60–80%) compared with Western cohorts (30–60%). 5 Within India, published data indicate prevalence rates ranging from 32% to 53%, reflecting regional heterogeneity. 5 However, evidence from the state of Kerala remains limited. Therefore, this study aimed to determine the prevalence of the BRAF V600E mutation in a cohort of patients with PTC from Kerala, India, and to evaluate its association with clinicopathological features, including age, gender, tumor size, nodal status, distant metastasis, lymph vascular/perineural invasion, and capsular invasion Materials and Methods This was a retrospective observational study conducted to determine the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) and to evaluate its association with clinicopathological features. The study was carried out in the Department of Pathology, Government Medical College Hospital, Thrissur, Kerala, India, over a two-year period from January 2021 to December 2022. All histopathological diagnosed cases of PTC in thyroidectomy specimens received during the study period were included. The study cohort comprised all patients who underwent complete or partial thyroidectomy for PTC at this tertiary care hospital during the specified period. Inclusion Criteria Complete or partial thyroidectomy specimens diagnosed as PTC Exclusion Criteria Specimens diagnosed with malignancies other than PTC Inadequate or non-representative samples Data Collection and Histopathological Evaluation Clinical details, including age, sex, and presenting information, were obtained from pathology requisition forms. All specimens were grossed following standard departmental protocols, and macroscopic features, including tumor size and extent, were recorded. Representative tissue sections were processed and stained with hematoxylin and eosin (H&E). Microscopic evaluation included assessment of histologic variant, tumor size, capsular invasion, extrathyroidal extension, lymphovascular invasion, lymph node metastasis, and multifocality. Immunohistochemistry for BRAF V600E Immunohistochemical (IHC) staining for BRAF V600E was performed on formalin-fixed, paraffin-embedded tumor tissue blocks. Due to the unavailability of a standardized automated IHC platform at the study center, tissue blocks were processed at an external reference facility. Staining was performed using the Roche (Ventana) Benchmark XT platform and the OptiView DAB IHC Detection Kit, with the anti-BRAF V600E (VE1) monoclonal antibody. Scoring of BRAF Expression Cytoplasmic staining intensity was graded on a 4-point scale: 0 : No staining 1 : Weak staining 2 : Moderate staining 3 : Strong staining Scores of 1–3 were considered positive for BRAF V600E expression, while a score of 0 was considered negative. Statistical Analysis Clinicopathological variables—including age, sex, TNM stage, multifocality, lymph vascular/perineural invasion, capsular invasion, and BRAF score—were tabulated in Microsoft Excel and analysed using SPSS software (version 27). Descriptive statistics (mean, median, and percentages) were used to summarize the data and mutation prevalence. Age distribution across BRAF score categories was compared using one-way ANOVA. Associations between BRAF status and categorical variables (gender, multifocality, tumor stage, nodal status, metastasis, lymphovascular/perineural invasion, and capsular invasion) were evaluated using Chi-square or Fisher’s exact tests. A p-value < 0.05 was considered statistically significant Results This retrospective study was conducted at the Surgery Department of Government Medical College, Thrissur, Kerala, India. We analyzed 69 patients who underwent total thyroidectomy for papillary thyroid carcinoma (PTC). Baseline clinicopathological characteristics are summarized in Table 1 . Table 1 Table 1 Baseline clinicopathological characteristics of patients with papillary thyroid carcinoma. Data presented as number (n) and percentage. LVI: lymphovascular invasion; PNI: perineural invasion; IHC: immunohistochemistry. Characteristic No. Percentage (%) Age (years) < 45 35 50.7% ≥ 45 34 49.3% Gender Female 51 73.9% Male 18 26.1% Tumor Size < 4 cm 56 81.2% ≥ 4 cm 13 18.8% Capsular Invasion Present 14 26.4% Absent 39 73.6% Lymph Node Status N0 (Negative) 10 14.5% N1 (Positive) 17 24.6% Nx (Not assessed) 42 60.9% Multifocality Present 22 31.9% Absent 47 68.1% LVI/PNI Present 23 33.3% Absent 46 66.7% BRAF V600E Status (IHC) Positive (scores 1–3) 46 66.7% Negative (score 0) 23 33.3% Total 69 100.0% Patient and Tumor Characteristics: Among the 69 patients, three-quarters were women, and the mean age was 44.8 years (SD 14.4), with an age range of 13 to 80 years. Additionally, 18.8% of tumours included in the study were larger than 4 cm in size. BRAF Score Distribution: The prevalence of BRAF-positive mutation in our study group was 66.7% (n = 46), of which 43.5% expressed strong positivity (a score of 3). The distribution of BRAF scores is shown in Table 2 Prevalence of BRAF scores BRAF Score Interpretation Number (n) Percentage (%) 0 Absent/Negative 23 33.3 1 Weak Positive 4 5.8 2 Moderate Positive 12 17.4 3 Strong Positive 30 43.5 Total 69 100.0 Overall BRAF Positive (scores 1–3): 46 (66.7%) Overall BRAF Negative (score 0): 23 (33.3%) Table 2 : Distribution of BRAF V600E mutation status based on immunohistochemistry scoring. Scores 1–3 considered positive for BRAF V600E mutation. Strong cytoplasmic staining scored as 3, moderate as 2, weak as 1, and absence of staining as 0. IHC performed using anti-BRAF V600E (VE1) antibody on Roche Ventana platform (Fig. 1 ) Clinicopathological Association of BRAF Mutation in PTC: The prevalence of BRAF mutation was 66.7% (46/69) in the study group. Among the tumor characteristics studied, only lymphovascular and perineural invasion (LVI/PNI) showed a significant association with BRAF-mutated tumors (p = 0.047, OR 3.34, 95% CI 0.98–11.41). Although the Chi-square test was not statistically significant, our cohort demonstrated that the odds of male patients with PTC having a BRAF mutation were double those of females (OR 2.08, 95% CI 0.59–7.24, p = 0.245). Table 3 : BRAF scores with clinicopathological association. Table 3 Association of BRAF scores with clinicopathological variables in 69 thyroid cancer patients Variable BRAF Negative (n = 23) BRAF Positive (n = 46) Total (n = 69) Odds Ratio (95% CI) p-value No. % No. % No. (%) Age (years), mean ± SD 44.04 ± 15.68 45.24 ± 13.93 44.82 ± 14.53 0.748 a Gender Female 19 37.3 32 62.7 51 (73.9) Ref. 0.245 Male 4 22.2 14 77.8 18 (26.1) 2.08 (0.597–7.24) Multifocal presentation No 15 31.9 32 68.1 47 (68.1) Ref. 0.715 Yes 8 36.4 14 63.6 22 (31.9) 0.82 (0.28–2.38) Tumor category T1–T2 20 35.7 36 64.3 56 (81.2) Ref. 0.520 T3–T4 3 23.1 10 76.9 13 (18.8) 1.85 (0.456–7.52) Nodal category b N0 (Negative) 2 20.0 8 80.0 10 (37.0) Ref. 0.401 N1 (Positive) 6 35.3 11 64.7 17 (63.0) 0.458 (0.073–2.89) Metastasis category M1 1 100.0 0 0.0 1 (1.4) — 0.333 MX 22 32.4 46 67.6 68 (98.6) — Lymphovascular/perineural invasion No 19 41.3 27 58.7 46 (66.7) Ref. 0.047* Yes 4 17.4 19 82.6 23 (33.3) 3.343 (0.98–11.41) Capsular invasion No 17 36.2 30 63.8 47 (68.1) Ref. 0.465 Yes 6 27.3 16 72.7 22 (31.9) 1.51 (0.497–4.59) a Mean difference − 1.196 (95% CI: −8.601 to 6.21) between BRAF negative and positive groups; values compared using independent t-test. b Nodal status assessed in 27 patients with available lymph node data. Discussion This retrospective study evaluated the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) and its association with key clinicopathological characteristics in a South Indian cohort. The mutation prevalence of 66.7% observed in this study is comparatively high. Although BRAF V600E is recognized as the most frequent genetic alteration in PTC worldwide, its distribution varies considerably across regions. Indian cohorts typically report an average prevalence rate of 46% (32–53%), whereas East Asian countries such as China, Japan, and South Korea frequently report rates exceeding 70% (71.2–76.4%). In contrast, European and North American series generally document lower rates, ranging from 35% to 60%, with mean values below 45%. The prevalence identified in the present study closely resembles that of East Asian populations and exceeds previously reported data from Kerala (51%) 5 , suggesting potential regional or ethnic variability within India. Several factors may explain this heterogeneity. Genetic diversity affecting molecular pathways central to thyroid tumorigenesis may contribute to inter-population differences. Environmental influences—including dietary iodine intake and radiation exposure—have also been implicated. Higher iodine consumption has been associated with increased BRAF V600E frequency 13 ; however, Kerala’s adequate iodine status does not fully account for the elevated prevalence observed 14 . Radiation exposure has been cited in regions such as Fukushima, Japan, where elevated BRAF mutation rates have been documented among young thyroid cancer patients 15 . Methodological factors—including variations in mutation detection techniques, histopathological interpretation, specimen handling, and evolving tumor classifications (such as post-2017 reclassification of NIFTP)—may further impact prevalence estimates 5˒16 . The immunohistochemistry-based method utilized in this study demonstrates up to 98% concordance with molecular assays 17 , supporting its validity, though non-V600E variants may remain undetected. This study identified significant associations between BRAF mutation and both lymphovascular and perineural invasion, suggesting a potential role in promoting local tumor aggressiveness. However, no significant associations were observed with age, multifocality, nodal metastasis, or distant metastasis. Earlier studies from Kerala reported a 51% mutation prevalence but found no association with aggressive pathological features 18 , whereas other Indian studies have demonstrated significant correlations between BRAF mutation and aggressive clinicopathological characteristics 19,20,21 The broader literature remains inconsistent. While some studies have linked BRAF V600E to poorer outcomes, recent meta-analyses and multicentre studies have questioned its prognostic utility. Javid et al. reported inconsistent associations between BRAF mutation and metastasis, recurrence, and mortality, limiting its role in risk stratification 16 . Similarly, Brumfield et al. (2025) demonstrated that although male gender and nodal metastasis predicted recurrence, BRAF mutation was not an independent predictor after adjustment for confounding variables 22 . Other studies have shown associations with lymph node metastasis but failed to establish predictive value for recurrence or survival 23 . Moreover, a systematic review by Wang et al. (2024) suggested that BRAF mutation may contribute to radioiodine resistance, indirectly influencing prognosis 24 . Emerging evidence indicates that integrating BRAF status with additional molecular markers—particularly TERT promoter mutations—may improve prognostic precision compared to reliance on BRAF alone 25 . These findings underscore the complexity of PTC carcinogenesis. A single mutation such as BRAF V600E may be insufficient to predict biological behaviour, as tumor progression likely involves multiple molecular pathways 26 .Consequently, combined molecular and clinicopathological assessment may offer a more robust framework for personalized risk stratification. Furthermore, 43.5% of BRAF-positive cases demonstrated strong (score 3) immunohistochemical expression, suggesting a possible link between mutation status and protein overexpression, which may have therapeutic implications. 27 This study carries limitations, including a relatively small sample size, retrospective design, and incomplete metastatic staging, which may restrict generalizability. Additionally, reliance on immunohistochemistry may not capture non-V600E variants. Kerala, a southern Indian state with a population exceeding 34 million, has health indicators comparable to developed nations 28 and has shown a rising incidence of thyroid cancer consistent with global trends 29 . Despite limitations, this study provides meaningful regional insight and highlights the significance of BRAF mutation in the molecular landscape of PTC in this population. Conclusion In summary, this study reports a high prevalence of BRAF V600E mutation (66.7%) among PTC patients in Kerala and identifies significant associations with lymphovascular and perineural invasion, with a possible trend toward male predominance. Although BRAF V600E alone remains an imperfect prognostic biomarker, its high prevalence underscores its likely role in PTC pathogenesis within this population. Larger, prospective studies incorporating comprehensive molecular profiling and longitudinal outcomes are warranted to refine risk stratification and inform personalized therapeutic strategies, including potential targeted treatments. Declarations Ethics Approval and Consent to Participate : This retrospective study was approved by the Institutional Ethics Committee, Government Medical College Thrissur, Kerala, India. All procedures were conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. Consent was waived due to the use of anonymized archival samples. Protocol NO: IEC/GMCTSR/244/2021 Consent to Publish: Not applicable. As no identifiable patient information is included in this manuscript. Ethics and Consent to Participate Declarations Ethics and Consent to Participate declarations: not applicable Data Availability: Data are available from the corresponding author on reasonable request. Competing Interests: The authors declare no competing interests. Funding: This study received funding from State Board of Medical Research (SBMR) Kerala, India References Bikas A, Burman KD. Epidemiology of thyroid cancer. 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13:43:56","extension":"html","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":88185,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8315000/v1/fbae4b26ba26492879437b5b.html"},{"id":100689371,"identity":"cb2a65f4-5d20-455d-ae82-dfb16ee347bc","added_by":"auto","created_at":"2026-01-20 13:41:37","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":135142,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative immunohistochemistry (IHC) images demonstrating BRAF V600E (VE1) staining patterns scored from 0 to 3.\u003c/p\u003e","description":"","filename":"RepresentativeIHCimagesofBRAFV600EstainingScores03.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8315000/v1/af8c33b32141bdad414b8013.jpg"},{"id":100683388,"identity":"94738ae0-32df-403d-9fb7-e6e531a529e2","added_by":"auto","created_at":"2026-01-20 12:31:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":995015,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8315000/v1/dbdb42fc-9408-4c3c-831b-86d3b2c237f0.pdf"},{"id":100689583,"identity":"e5730b14-8053-4595-b904-fb773fd399c8","added_by":"auto","created_at":"2026-01-20 13:43:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":78175,"visible":true,"origin":"","legend":"","description":"","filename":"CertificateIEC244SanthoshTV.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8315000/v1/1b881951718faa91b4f7c04e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prevalence and Clinicopathological Significance of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Retrospective Cohort Study from Kerala, India","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePapillary thyroid carcinoma (PTC) is the most common endocrine malignancy worldwide, accounting for approximately 75\u0026ndash;85% of all thyroid cancers.\u0026sup1;Although PTC is associated with an excellent prognosis, with a 10-year survival rate exceeding 90%,\u0026sup1; a subset of tumors demonstrates aggressive behaviour, including extrathyroidal extension, lymph node metastasis, and reduced sensitivity to radioiodine therapy, which may adversely affect long-term outcomes.\u003csup\u003e2,3\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eRecent advances in molecular oncology have identified several genetic alterations involved in thyroid tumorigenesis, particularly within the mitogen-activated protein kinase (MAPK) signalling pathway.\u003csup\u003e4\u003c/sup\u003e Among these, the BRAF V600E mutation is the most prevalent, reported in 45\u0026ndash;80% of PTC cases, with notable geographic variation.\u003csup\u003e5,6\u003c/sup\u003eThe BRAF gene encodes a serine\u0026ndash;threonine kinase that regulates follicular cell growth and differentiation. A valine-to-glutamic acid substitution at codon 600 (V600E) results in constitutive activation of the MAPK pathway, leading to uncontrolled cellular proliferation.\u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eNumerous studies have examined the clinicopathological significance of the BRAF V600E mutation in PTC. Most have reported associations with adverse features such as extrathyroidal extension, lymph node metastasis, advanced tumor stage, and increased recurrence risk.\u003csup\u003e8,9,10\u003c/sup\u003eHowever, other studies have not demonstrated such associations, suggesting that the prognostic impact of BRAF V600E may be influenced by additional genetic, environmental, or epigenetic factors.\u003csup\u003e11,12\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe prevalence of BRAF V600E shows considerable regional variation, with higher rates reported in Asian populations (60\u0026ndash;80%) compared with Western cohorts (30\u0026ndash;60%).\u003csup\u003e5\u003c/sup\u003e Within India, published data indicate prevalence rates ranging from 32% to 53%, reflecting regional heterogeneity.\u003csup\u003e5\u003c/sup\u003eHowever, evidence from the state of Kerala remains limited.\u003c/p\u003e \u003cp\u003eTherefore, this study aimed to determine the prevalence of the BRAF V600E mutation in a cohort of patients with PTC from Kerala, India, and to evaluate its association with clinicopathological features, including age, gender, tumor size, nodal status, distant metastasis, lymph vascular/perineural invasion, and capsular invasion\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis was a retrospective observational study conducted to determine the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) and to evaluate its association with clinicopathological features. The study was carried out in the Department of Pathology, Government Medical College Hospital, Thrissur, Kerala, India, over a two-year period from January 2021 to December 2022. All histopathological diagnosed cases of PTC in thyroidectomy specimens received during the study period were included. The study cohort comprised all patients who underwent complete or partial thyroidectomy for PTC at this tertiary care hospital during the specified period.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eInclusion Criteria\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eComplete or partial thyroidectomy specimens diagnosed as PTC\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eExclusion Criteria\u003c/h3\u003e\n\u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eSpecimens diagnosed with malignancies other than PTC\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eInadequate or non-representative samples\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e\n\u003ch3\u003eData Collection and Histopathological Evaluation\u003c/h3\u003e\n\u003cp\u003eClinical details, including age, sex, and presenting information, were obtained from pathology requisition forms. All specimens were grossed following standard departmental protocols, and macroscopic features, including tumor size and extent, were recorded.\u003c/p\u003e \u003cp\u003eRepresentative tissue sections were processed and stained with hematoxylin and eosin (H\u0026amp;E). Microscopic evaluation included assessment of histologic variant, tumor size, capsular invasion, extrathyroidal extension, lymphovascular invasion, lymph node metastasis, and multifocality.\u003c/p\u003e\n\u003ch3\u003eImmunohistochemistry for BRAF V600E\u003c/h3\u003e\n\u003cp\u003eImmunohistochemical (IHC) staining for BRAF V600E was performed on formalin-fixed, paraffin-embedded tumor tissue blocks. Due to the unavailability of a standardized automated IHC platform at the study center, tissue blocks were processed at an external reference facility. Staining was performed using the Roche (Ventana) Benchmark XT platform and the OptiView DAB IHC Detection Kit, with the anti-BRAF V600E (VE1) monoclonal antibody.\u003c/p\u003e\n\u003ch3\u003eScoring of BRAF Expression\u003c/h3\u003e\n\u003cp\u003eCytoplasmic staining intensity was graded on a 4-point scale:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003e0\u003c/b\u003e: No staining\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003e1\u003c/b\u003e: Weak staining\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003e2\u003c/b\u003e: Moderate staining\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003e3\u003c/b\u003e: Strong staining\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eScores of 1\u0026ndash;3 were considered positive for BRAF V600E expression, while a score of 0 was considered negative.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eClinicopathological variables\u0026mdash;including age, sex, TNM stage, multifocality, lymph vascular/perineural invasion, capsular invasion, and BRAF score\u0026mdash;were tabulated in Microsoft Excel and analysed using SPSS software (version 27).\u003c/p\u003e \u003cp\u003eDescriptive statistics (mean, median, and percentages) were used to summarize the data and mutation prevalence. Age distribution across BRAF score categories was compared using one-way ANOVA. Associations between BRAF status and categorical variables (gender, multifocality, tumor stage, nodal status, metastasis, lymphovascular/perineural invasion, and capsular invasion) were evaluated using Chi-square or Fisher\u0026rsquo;s exact tests. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThis retrospective study was conducted at the Surgery Department of Government Medical College, Thrissur, Kerala, India. We analyzed 69 patients who underwent total thyroidectomy for papillary thyroid carcinoma (PTC). Baseline clinicopathological characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline clinicopathological characteristics of patients with papillary thyroid carcinoma. Data presented as number (n) and percentage. LVI: lymphovascular invasion; PNI: perineural invasion; IHC: immunohistochemistry.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e73.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor Size\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;4 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e81.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCapsular Invasion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e73.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymph Node Status\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN0 (Negative)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1 (Positive)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNx (Not assessed)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMultifocality\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e68.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLVI/PNI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBRAF V600E Status (IHC)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive (scores 1\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative (score 0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e69\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e100.0%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003ePatient and Tumor Characteristics:\u003c/h3\u003e\n\u003cp\u003eAmong the 69 patients, three-quarters were women, and the mean age was 44.8 years (SD 14.4), with an age range of 13 to 80 years. Additionally, 18.8% of tumours included in the study were larger than 4 cm in size.\u003c/p\u003e \u003cp\u003eBRAF Score Distribution:\u003c/p\u003e \u003cp\u003eThe prevalence of BRAF-positive mutation in our study group was 66.7% (n\u0026thinsp;=\u0026thinsp;46), of which 43.5% expressed strong positivity (a score of 3). The distribution of BRAF scores is shown in\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrevalence of BRAF scores\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBRAF Score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInterpretation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsent/Negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWeak Positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModerate Positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStrong Positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e69\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e100.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eOverall BRAF Positive (scores 1\u0026ndash;3): 46 (66.7%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eOverall BRAF Negative (score 0): 23 (33.3%)\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e: Distribution of BRAF V600E mutation status based on immunohistochemistry scoring. Scores 1\u0026ndash;3 considered positive for BRAF V600E mutation. Strong cytoplasmic staining scored as 3, moderate as 2, weak as 1, and absence of staining as 0. IHC performed using anti-BRAF V600E (VE1) antibody on Roche Ventana platform (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eClinicopathological Association of BRAF Mutation in PTC:\u003c/h2\u003e \u003cp\u003eThe prevalence of BRAF mutation was 66.7% (46/69) in the study group. Among the tumor characteristics studied, only lymphovascular and perineural invasion (LVI/PNI) showed a significant association with BRAF-mutated tumors (p\u0026thinsp;=\u0026thinsp;0.047, OR 3.34, 95% CI 0.98\u0026ndash;11.41). Although the Chi-square test was not statistically significant, our cohort demonstrated that the odds of male patients with PTC having a BRAF mutation were double those of females (OR 2.08, 95% CI 0.59\u0026ndash;7.24, p\u0026thinsp;=\u0026thinsp;0.245).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e: BRAF scores with clinicopathological association.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation of BRAF scores with clinicopathological variables in 69 thyroid cancer patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBRAF Negative (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBRAF Positive (n\u0026thinsp;=\u0026thinsp;46)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;69)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOdds Ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.04\u0026thinsp;\u0026plusmn;\u0026thinsp;15.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45.24\u0026thinsp;\u0026plusmn;\u0026thinsp;13.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44.82\u0026thinsp;\u0026plusmn;\u0026thinsp;14.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.748\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51 (73.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.245\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e77.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18 (26.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.08 (0.597\u0026ndash;7.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMultifocal presentation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47 (68.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.715\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22 (31.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.82 (0.28\u0026ndash;2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor category\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT1\u0026ndash;T2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e56 (81.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.520\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3\u0026ndash;T4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.85 (0.456\u0026ndash;7.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNodal category\u003c/b\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN0 (Negative)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10 (37.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.401\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1 (Positive)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17 (63.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.458 (0.073\u0026ndash;2.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMetastasis category\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.333\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e68 (98.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymphovascular/perineural invasion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.047*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e82.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.343 (0.98\u0026ndash;11.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCapsular invasion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47 (68.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.465\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22 (31.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.51 (0.497\u0026ndash;4.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003ea\u003c/sup\u003e Mean difference \u0026minus;\u0026thinsp;1.196 (95% CI: \u0026minus;8.601 to 6.21) between BRAF negative and positive groups; values compared using independent t-test.\u003c/p\u003e \u003cp\u003e \u003csup\u003eb\u003c/sup\u003e Nodal status assessed in 27 patients with available lymph node data.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective study evaluated the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) and its association with key clinicopathological characteristics in a South Indian cohort. The mutation prevalence of 66.7% observed in this study is comparatively high. Although BRAF V600E is recognized as the most frequent genetic alteration in PTC worldwide, its distribution varies considerably across regions. Indian cohorts typically report an average prevalence rate of 46% (32\u0026ndash;53%), whereas East Asian countries such as China, Japan, and South Korea frequently report rates exceeding 70% (71.2\u0026ndash;76.4%). In contrast, European and North American series generally document lower rates, ranging from 35% to 60%, with mean values below 45%. The prevalence identified in the present study closely resembles that of East Asian populations and exceeds previously reported data from Kerala (51%)\u003csup\u003e5\u003c/sup\u003e, suggesting potential regional or ethnic variability within India.\u003c/p\u003e \u003cp\u003eSeveral factors may explain this heterogeneity. Genetic diversity affecting molecular pathways central to thyroid tumorigenesis may contribute to inter-population differences. Environmental influences\u0026mdash;including dietary iodine intake and radiation exposure\u0026mdash;have also been implicated. Higher iodine consumption has been associated with increased BRAF V600E frequency\u003csup\u003e13\u003c/sup\u003e; however, Kerala\u0026rsquo;s adequate iodine status does not fully account for the elevated prevalence observed\u003csup\u003e14\u003c/sup\u003e. Radiation exposure has been cited in regions such as Fukushima, Japan, where elevated BRAF mutation rates have been documented among young thyroid cancer patients\u003csup\u003e15\u003c/sup\u003e. Methodological factors\u0026mdash;including variations in mutation detection techniques, histopathological interpretation, specimen handling, and evolving tumor classifications (such as post-2017 reclassification of NIFTP)\u0026mdash;may further impact prevalence estimates\u003csup\u003e5˒16\u003c/sup\u003e. The immunohistochemistry-based method utilized in this study demonstrates up to 98% concordance with molecular assays\u003csup\u003e17\u003c/sup\u003e, supporting its validity, though non-V600E variants may remain undetected.\u003c/p\u003e \u003cp\u003eThis study identified significant associations between BRAF mutation and both lymphovascular and perineural invasion, suggesting a potential role in promoting local tumor aggressiveness. However, no significant associations were observed with age, multifocality, nodal metastasis, or distant metastasis. Earlier studies from Kerala reported a 51% mutation prevalence but found no association with aggressive pathological features\u003csup\u003e18\u003c/sup\u003e, whereas other Indian studies have demonstrated significant correlations between BRAF mutation and aggressive clinicopathological characteristics\u003csup\u003e19,20,21\u003c/sup\u003e The broader literature remains inconsistent. While some studies have linked BRAF V600E to poorer outcomes, recent meta-analyses and multicentre studies have questioned its prognostic utility. Javid et al. reported inconsistent associations between BRAF mutation and metastasis, recurrence, and mortality, limiting its role in risk stratification\u003csup\u003e16\u003c/sup\u003e. Similarly, Brumfield et al. (2025) demonstrated that although male gender and nodal metastasis predicted recurrence, BRAF mutation was not an independent predictor after adjustment for confounding variables\u003csup\u003e22\u003c/sup\u003e. Other studies have shown associations with lymph node metastasis but failed to establish predictive value for recurrence or survival\u003csup\u003e23\u003c/sup\u003e. Moreover, a systematic review by Wang et al. (2024) suggested that BRAF mutation may contribute to radioiodine resistance, indirectly influencing prognosis\u003csup\u003e24\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eEmerging evidence indicates that integrating BRAF status with additional molecular markers\u0026mdash;particularly TERT promoter mutations\u0026mdash;may improve prognostic precision compared to reliance on BRAF alone\u003csup\u003e25\u003c/sup\u003e. These findings underscore the complexity of PTC carcinogenesis. A single mutation such as BRAF V600E may be insufficient to predict biological behaviour, as tumor progression likely involves multiple molecular pathways\u003csup\u003e26\u003c/sup\u003e.Consequently, combined molecular and clinicopathological assessment may offer a more robust framework for personalized risk stratification.\u003c/p\u003e \u003cp\u003eFurthermore, 43.5% of BRAF-positive cases demonstrated strong (score 3) immunohistochemical expression, suggesting a possible link between mutation status and protein overexpression, which may have therapeutic implications.\u003csup\u003e27\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThis study carries limitations, including a relatively small sample size, retrospective design, and incomplete metastatic staging, which may restrict generalizability. Additionally, reliance on immunohistochemistry may not capture non-V600E variants.\u003c/p\u003e \u003cp\u003eKerala, a southern Indian state with a population exceeding 34\u0026nbsp;million, has health indicators comparable to developed nations\u003csup\u003e28\u003c/sup\u003e and has shown a rising incidence of thyroid cancer consistent with global trends\u003csup\u003e29\u003c/sup\u003e. Despite limitations, this study provides meaningful regional insight and highlights the significance of BRAF mutation in the molecular landscape of PTC in this population.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, this study reports a high prevalence of BRAF V600E mutation (66.7%) among PTC patients in Kerala and identifies significant associations with lymphovascular and perineural invasion, with a possible trend toward male predominance. Although BRAF V600E alone remains an imperfect prognostic biomarker, its high prevalence underscores its likely role in PTC pathogenesis within this population. Larger, prospective studies incorporating comprehensive molecular profiling and longitudinal outcomes are warranted to refine risk stratification and inform personalized therapeutic strategies, including potential targeted treatments.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThis retrospective study was approved by the Institutional Ethics Committee, Government Medical College Thrissur, Kerala, India. All procedures were conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. Consent was waived due to the use of anonymized archival samples.\u003cbr\u003e\u0026nbsp;Protocol NO: IEC/GMCTSR/244/2021\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. As no identifiable patient information is included in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics and Consent to Participate Declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics and Consent to Participate declarations: not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received funding from State Board of Medical Research (SBMR) Kerala, India\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e Bikas A, Burman KD. Epidemiology of thyroid cancer. In: Luster M, Duntas L, Wartofsky L, editors. \u003cem\u003eThe Thyroid and Its Diseases\u003c/em\u003e. Cham: Springer; 2019. p. 541\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Grogan RH, Kaplan SP, Cao H, Weiss RE, DeGroot LJ, Simon CA, et al. A study of recurrence and death from papillary thyroid cancer with 27 years of median follow-up. \u003cem\u003eSurgery\u003c/em\u003e. 2013;154(6):1436\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Toraih EA, Hussein MH, Zerfaoui M, et al. Site-specific metastasis and survival in papillary thyroid cancer: the importance of brain and multi-organ disease. \u003cem\u003eCancers (Basel)\u003c/em\u003e. 2021;13(7):1625.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Cancer Genome Atlas Research Network. 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MAP kinase signalling pathways in cancer. \u003cem\u003eOncogene\u003c/em\u003e. 2007;26(22):3279\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Tufano RP, Teixeira GV, Bishop J, Carson KA, Xing M. BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: a systematic review and meta-analysis. \u003cem\u003eMedicine (Baltimore)\u003c/em\u003e. 2012;91(5):274\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Liu R, Bishop J, Zhu G, Zhang T, Ladenson PW, Xing M. Mortality risk stratification by combining BRAF V600E and TERT promoter mutations in papillary thyroid cancer. \u003cem\u003eJAMA Oncol\u003c/em\u003e. 2017;3(2):202\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Ma H, Wang R, Fang J, Zhong Q, Chen X, Hou L, et al. Relationship between BRAF mutation and cervical lymphatic metastasis in papillary thyroid cancer: a meta-analysis. \u003cem\u003eMedicine (Baltimore)\u003c/em\u003e. 2020;99(5):e18917.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Gouveia C, Can NT, Bostrom A, Grenert JP, van Zante A, Orloff LA. Lack of association of BRAF mutation with negative prognostic indicators in papillary thyroid carcinoma. \u003cem\u003eJAMA Otolaryngol Head Neck Surg\u003c/em\u003e. 2013;139(11):1164\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Goh X, Lum J, Yang SP, Chionh SB, Koay E, Chiu L, et al. BRAF mutation in papillary thyroid cancer: prevalence and clinical correlation in a South-East Asian cohort. \u003cem\u003eClin Otolaryngol\u003c/em\u003e. 2019;44(2):114\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Guan H, Ji M, Bao R, Yu H, Wang Y, Hou P, et al. Association of high iodine intake with the T1799A BRAF mutation in papillary thyroid cancer. \u003cem\u003eJ Clin Endocrinol Metab\u003c/em\u003e. 2009;94:1612\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Brief C. Status of the iodine nutrition and salt iodization program. 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Guerra A, Fugazzola L, Marotta V, et al. High percentage of BRAFV600E alleles predicts poorer outcome in papillary thyroid carcinoma. \u003cem\u003eJ Clin Endocrinol Metab\u003c/em\u003e. 2012;97:2333\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Javid M. Questioning the role of BRAF V600E as a prognostic indicator in papillary thyroid carcinoma. \u003cem\u003eAnn Surg Oncol\u003c/em\u003e. 2025;32(5):3060\u0026ndash;1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Zimmermann AK, Camenisch U, Rechsteiner MP, Bode-Lesniewska B, Rossle M. Value of immunohistochemistry in detecting BRAFV600E mutation in thyroid FNA. \u003cem\u003eCancer Cytopathol\u003c/em\u003e. 2014;122(1):48\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Nair CG, Babu M, Biswas L, Jacob P, Menon R, Revathy AK, et al. Lack of association of BRAF V600E mutation with high-risk tumor features and adverse outcome in papillary thyroid carcinoma. Indian J Endocrinol Metab. 2017;21(2):329\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Chakraborty A, Narkar A, Mukhopadhyaya R, Kane S, D'Cruz A, Rajan MG. BRAF V600E mutation in papillary thyroid carcinoma: significant association with node metastases and extrathyroidal invasion. Endocr Pathol. 2012;23(2):83\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Agarwal S, Sharma MC, Karak AK, Bal CS, Chopra MK, Chumber S. BRAF mutation may predict higher risk of incomplete response to radioactive iodine ablation in papillary thyroid carcinoma. Indian J Endocrinol Metab. 2017;21(1):1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Ahmad F, Nathani R, Venkat J, et al. Molecular evaluation of BRAF mutation in thyroid tumors. \u003cem\u003eExp Mol Pathol\u003c/em\u003e. 2018;105:380\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Brumfield A, Azar SA, Nordgren R, et al. Prevalence and clinical impact of BRAF p.V600E in papillary thyroid carcinoma. \u003cem\u003eEndocr Pathol\u003c/em\u003e. 2025;36(1):13\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Onco S, et al. Relationship between BRAF V600E and prognostic factors in papillary thyroid cancer. \u003cem\u003eOncol Clin Pract\u003c/em\u003e. 2025;104(4):320\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Wang B, Cen X, Zhang B, Zhang W. Effect of BRAFV600E on radioiodine therapy in PTC: a systematic review. \u003cem\u003eFront Endocrinol\u003c/em\u003e. 2024;15:XXXXX.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Wang Y, et al. Prediction of BRAF and TERT status in PTC by machine learning. \u003cem\u003eFront Endocrinol\u003c/em\u003e. 2025;16:1012.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Boucai L, Seshan V, Williams M, Knauf JA, Saqcena M, Ghossein RA, et al. Subtypes of BRAF-mutant PTC defined by thyroid differentiation score. \u003cem\u003eJ Clin Endocrinol Metab\u003c/em\u003e. 2022;107(4):1030\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Scheffel RS, Dora JM, Maia AL. BRAF mutations in thyroid cancer. \u003cem\u003eCurr Opin Oncol\u003c/em\u003e. 2022;34(1):9\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e 30Adithyan GS, Ranjan A, Muraleedharan VR, Sundararaman T. Kerala\u0026rsquo;s progress toward UHC. \u003cem\u003eInt J Equity Health\u003c/em\u003e. 2024;23:152.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e 31Mathew IE, Mathew A. Rising thyroid cancer incidence in Southern India. \u003cem\u003eJ Endocr Soc\u003c/em\u003e. 2017;1(5):480\u0026ndash;\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"BRAF V600E, papillary thyroid carcinoma, immunohistochemistry, clinicopathological factors, lymphovascular invasion","lastPublishedDoi":"10.21203/rs.3.rs-8315000/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8315000/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe BRAF V600E mutation is the most frequent genetic alteration in papillary thyroid carcinoma (PTC) and has been implicated in aggressive tumor behaviour. Its prevalence, however, varies across populations. This study aimed to determine the prevalence of BRAF V600E mutation in a South Indian PTC cohort and to evaluate its association with clinicopathological features.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTumor specimens from 69 patients with histologically confirmed PTC were subjected to immunohistochemical analysis for BRAF V600E expression. Staining intensity was graded from 0 to 3, with scores\u0026thinsp;\u0026gt;\u0026thinsp;0 defined as positive. Age distribution across score categories was assessed using one-way ANOVA. Associations between BRAF status and clinicopathological variables\u0026mdash;including gender, multifocality, tumor stage, nodal status, metastasis, lymphovascular/perineural invasion (LVI/PNI), and capsular invasion\u0026mdash;were analyzed using Chi-square or Fisher\u0026rsquo;s exact tests. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eBRAF V600E positivity was detected in 66.7% (46/69) of cases, with 43.5% of positive tumors demonstrating strong expression (score 3). Among the evaluated parameters, only LVI/PNI showed a significant association with BRAF positivity (p\u0026thinsp;=\u0026thinsp;0.047; OR 3.34; 95% CI 0.98\u0026ndash;11.41). No significant associations were observed between BRAF status and age, gender, T stage, N stage, or distant metastasis.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis cohort demonstrated a high prevalence of BRAF V600E mutation in PTC. Its significant association with LVI/PNI suggests a potential link with invasive tumor behaviour. Although limited by sample size and retrospective design, these findings support further prospective research to clarify the prognostic utility of BRAF V600E and its relevance in risk stratification and targeted therapy in PTC.\u003c/p\u003e","manuscriptTitle":"Prevalence and Clinicopathological Significance of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Retrospective Cohort Study from Kerala, India","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-20 11:29:02","doi":"10.21203/rs.3.rs-8315000/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-05T10:22:18+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-05T09:13:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-31T12:17:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-21T07:24:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"164533706858211395905263915471444448321","date":"2026-01-20T03:55:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-19T10:02:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"215200441890991984623057102805250261591","date":"2026-01-19T09:28:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-19T07:14:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"150523219951301168172383571187878522506","date":"2026-01-19T06:44:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-19T05:29:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"265465090520866949265055057721219167194","date":"2026-01-18T15:33:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7111138307321383454654016251612083034","date":"2026-01-18T13:53:56+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-17T14:59:56+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-17T06:34:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"197526052246575923772042999576688510260","date":"2026-01-17T03:12:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"78476932898939479870900558761410664270","date":"2026-01-16T11:12:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"242732819950491179155632962787683804209","date":"2026-01-16T09:26:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-16T09:16:11+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-18T09:06:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-16T22:37:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-16T22:37:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2025-12-09T08:07:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"15780f0c-3f1e-4e3d-b5f9-6e6c904dfe5d","owner":[],"postedDate":"January 20th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T15:20:59+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-20 11:29:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8315000","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8315000","identity":"rs-8315000","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}