A study of microenvironment in invasive breast cancer-Tumor infiltrating lymphocytes and Stromal CD10 do not correlate with tumor grade and molecular subtypes

A study of microenvironment in invasive breast cancer-Tumor infiltrating lymphocytes and Stromal CD10 do not correlate with tumor grade and molecular subtypes | 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 A study of microenvironment in invasive breast cancer-Tumor infiltrating lymphocytes and Stromal CD10 do not correlate with tumor grade and molecular subtypes Alina Basnet, Shreya Shrivastav, Abhimanyu Jha This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8591422/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Breast cancer is the second most common cancer among women worldwide. Tumor microenvironment which constitutes fibroblasts, myofibroblasts, mesenchymal stem cells, adipocytes, tumor-infiltrating lymphocytes (TILs) and endothelial cells facilitates progression and development of cancer. CD10 which is expressed in the stromal cells is thought to be associated with the aggressiveness of breast cancer. The presence of TILs within the peritumoral stroma is an important biomarker that reflects antitumor immune response in breast cancer especially in HER-2 positive and Triple-negative breast cancers. Methods The study was undertaken with the objective to evaluate expression of Tumor Infiltrating lymphocytes and Stromal CD10 in Breast carcinoma. This was an analytical and cross-sectional study conducted from February 3, 2021, to February 2, 2022. Forty eight cases including core biopsies, excisional biopsies and mastectomies were evaluated for Stromal CD10 and 30 excisional biopsies were evaluated for TIL. Age, sex and laterality of the specimens were recorded. CD10 and TILs expression was determined in relation to histological grade and intrinsic molecular subtype. Results Forty eight cases of invasive breast carcinoma were studied. Total 16 cases were positive for stromal CD10 (33%). All the cases of grade 3 tumor were stromal CD10 positive. Triple negative cases showed highest frequency of cases with CD10 positivity (41%). TIL was evaluated only in 30 of the cases, as they were resection specimens, according to International TIL Working group 2014. Sixteen of these cases (53%) showed low TIL which was most common in grade 1 tumor followed by grade 2. TIL expression was high to intermediate most frequently in Triple-negative, HER-2 enriched and Luminal A subtypes constituting four cases each. Conclusion CD10 expression was detected in almost one third of cases of which expression was highest in Triple negative breast cancers and was 100% in grade 3 tumors. Low TIL was detected in about 53% of cases followed by intermediate TIL in 44% of cases. High to intermediate TIL was seen in Triple-negative breast cancers and HER-2 enriched tumors most frequently. Breast carcinoma CD10 tumor microenvironment Tumor-infiltrating lymphocytes Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Breast cancer is the most common cancer globally. In Nepal, it is the third most common cancer overall and second most common cancer among women after cervix, according to statistics released by International Agency for Research on Cancer (IARC) [ 1 ] in December 2020. The most important risk factor to breast carcinoma are gender, age, hormones levels and family history. One third of breast cancer occurs due to mutation of tumor suppressor genes in BRCA1 and BRCA2 with family history. The prognosis of breast carcinoma depends upon stage, histological grade, lymph node status, ER/PR and HER2-neu status. An additional factor that is associated with prognosis includes Tumor microenvironment. Although breast cancer is an epithelial carcinoma of terminal ductal lobular unit the stromal microenvironment plays an important role in its evolution and metastasis. Tumor-Infiltrating Lymphocytes (TIL) have been emerging as important prognostic marker as different studies have indicated that it has been strongly associated with some specific types of breast cancer[ 2 ]. CD10 is a common acute lymphoblastic leukemia antigen which is zinc dependent metalloprotease and is normally expressed in epithelial cells[ 3 ]. Expression of stromal CD10 is associated with aggressive breast cancer[ 4 ]. As, the incidence of breast carcinoma is increasing, the relation of tumor with tumor microenvironment is currently under research as it can help in determining the prognostic and predictive evaluation of the tumor[ 5 ]. Materials This is an analytical and cross-sectional study conducted from February 3, 2021, to February 2, 2022. A total of 8686 biopsies and resection specimens were received in the Department of Pathology, Tribhuvan University Teaching Hospital, Nepal. A total 80 cases (0.9%) core needle biopsies and excision biopsy specimens were received and morphologically diagnosed as Invasive Breast Carcinoma. Cases for which an both core biopsy and excisional biopsy were available, only the excisional biopsy was included. Eighteen cases that had undergone neo-adjuvant chemotherapy and 2 cases with scanty material were excluded with a final sample size of 48. Age, sex and laterality of the specimens were recorded. Histopathological examination, grading and staging were done. Immunohistochemistry for molecular typing was performed. Additional Immunohistochemistry (IHC) for CD10 done. CD 10 and TILs expression in relation to histological grade, Intrinsic molecular subtype was determined. The Statistical analysis for this study was done using the software IBM Statistical Package for social science (SPSS) version 25. The correlation between Tumor Infiltrating Lymphocytes and stromal CD10 histopathological grade and intrinsic molecular subtypes was made and strength of association was calculated by Fishers exact test and p value less than 0.05 are considered statistically significant. Interpretation and scoring system IHC for ER, PR and HER2 were scored according to CAP protocol 2019. CD10: CD10 expression was evaluated in stroma around breast cancer. More than 10% expression in stromal cells was considered to be positive. Tumor infiltrative lymphocytes (TILS): Percentage of TILs were evaluated only of resection specimen, and classified as 0–10% (Low), 20–40% (Intermediate) and 50–90%(High) as per the evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Results During the study period between February 2022 to February 2023, of all biopsies received in Tribhuvan University Teaching Hospital, there were total of 80 cases (0.9%) diagnosed as invasive breast carcinoma. After application of the inclusion and exclusion criteria, total 48 cases were included in the study. All of the cases were female. The age of the patients ranged from 30 to 79 years with a mean age of 52 years. The highest number of cases were in the range of 50-59years (29%). The youngest age of presentation was 30 years. The age distribution of the cases is shown in figure 1. The right breast was affected more frequently than the left breast with 60% cases occurring in the right breast. There were no cases of bilateral carcinoma. The commonest histological subtype in this study is Invasive Ductal Carcinoma –No Special Type which constituted 44 cases (92%) and other subtypes were two cases of mucinous carcinoma (4%), one case of metaplastic carcinoma (2%) and one case of invasive lobular carcinoma (2%). Table 1shows the distribution of cases according to grade and according to molecular subtypes among core biopsy specimens and among mastectomy and lumpectomy specimens. Results for Expression of CD10: Total 16 cases were positive for Stromal CD10 (33%) and 32 cases were negative (67%) as shown if figure 2. The expression of CD10 is shown in detail in Table1. All the cases of Grade 3 tumor were positive whereas, only 30% of grade 1 and grade 2 tumors were positive for CD10. However, CD10 staining is not statistically significant with histological grade ( p- value 0.185) as shown in Table 2. Triple negative cases showed highest percentage of cases with CD10 positivity (41%) followed by luminal A (33%).There is no statistical correlation between CD10 expression and molecular subtypes ( p-value 0.929) as shown in table 3. Result for Tumor infiltrating lymphocytes. TIL was evaluated according to International TILs Working group (2014), which recommends full sections over core biopsies. Therefore only the thirty cases of excisional specimens were included in evaluation of TIL and core biopsies were excluded. TIL was assessed as low, intermediate and high based upon the International TILs Working group. Fifty three percent cases showed low TIL,44% cases showed intermediate TIL and 3% cases showed high TIL (Figure 3). Sixteen of total thirty (53%) showed low TIL which was most common in grade 1 tumor followed by grade 2. Out of 13 cases of (44%) intermediate TIL expression, equal TIL expression was seen in grade1 and grade 2 tumors. High TIL was expressed only in 1 case of grade 2 tumor and not in any of the Grade I and Grade III tumors as shown in table 4. Intermediate-high TIL expression was highest in Luminal A, Triple- negative and HER-2 enriched subtype constituting four cases each. High TIL was seen only in one case with Triple-negative subtype. Figure 4 shows representative photomicrographs of different CD10 staining and variable degrees of TIL. Discussion The evolution of breast cancer is poorly understood due to its heterogeneity. The major cause is due to multiple genetic changes affecting numerous genes. Tumor microenvironment which constitutes fibroblasts, myofibroblasts, mesenchymal stem cells, adipocytes, tumor-infiltrating lymphocytes and endothelial cells facilitates development and progression of cancer. Forty eight cases of invasive breast carcinoma were included in the present study. Majority of patients were 40–60 years of age (77%) with a mean of 52 years. The youngest age of presentation was 30 years. This was similar to studies conducted by Kandamuthan et al.[ 6 ], Thapa. et al.[ 7 ] and Duong et al.[ 8 ] However, the age of presentation is much older in some countries including the USA as shown in a survey between 2018–2022[ 9 ]. In most studies, left breast was the more common side involved by breast carcinoma[ 7 , 8 , 10 ]. However, our study revealed right breast as the commonest side (60%) involved by the cancer. Although breast cancer can occur in male breast, in present study all the cases were female[ 11 ]. CD10 which is expressed in stromal cells is associated with the aggressiveness of breast cancer[ 12 ]. Various studies have revealed CD10 expression is associated with higher histological grade and frequency of CD10 expression is higher in TNBCs[ 13 – 15 ]. In our study, we used scoring system for CD10 based on Iwaya et al. where more than 10% of the stromal cells around breast cancer cells is considered positive for CD10[ 16 ]. Our study showed stromal CD10 positivity only in 16 cases (33%) with 67% of cases being negative for CD10. This was similar to the findings of a study done by Iwaya et al.[ 16 ] in which CD10 positivity was 18%. However studies done by Raziq et al.[ 17 ], Puri et al.[ 18 ], Marketsov et al.[ 13 ] revealed much higher CD10 positivity of 56%, 80% and 79% respectively. In our study two cases (100%) of grade 3 tumors, seven cases (30%) of grade 2 tumors and seven cases (30%) of grade 1 tumors showed CD10 positivity. Seventy percent of grade 1 tumor and grade 2 tumor each were CD10 negative. Statistical correlation between CD10 and grade ( p-value 0.185) was not found. This was similar to the findings of the study done by Puri et al.[ 18 ], Sharma et al.[ 19 ], Raziq et al. [ 17 ] which showed no correlation of tumor grade with CD10. The findings are contradictory to those found in study byMakestov et al.[ 13 ] where significant correlation was found between stromal CD10 positivity and increasing tumor grade. The discrepancy in stromal CD10 expression and tumor grade could be because higher number of cases included in their studies, which was four hundred thirty eight. In their studies number of grade 3 tumor were higher as compared to our study (2 cases). In contrast to various studies, our study showed 30% CD10 positivity in grade 1 tumor as well. In the present study Triple negative cases showed highest frequency of CD10 positivity (41%) followed by luminal A (33%), HER-2 enriched (30%) and Luminal B (27%) subtype. Luminal B subtype showed most CD10 negativity (73%). There was no statistical correlation between CD10 expression and molecular subtypes ( p-value 0.929) as shown in Table 3 . Our finding is similar to the study of Louhichi et al.[ 20 ] Louchichi et al. revealed stromal CD10 expression in 24.3% of Triple-negative tumors, 31.2% of HER-2 enriched, 14% of Luminal A and 3% of Luminal B tumors. A study by Livasy et al. revealed CD10 stromal positivity in fewer cases, i.e.11% of Triple-negative cases and 8% of HER-2 enriched. There was no Stromal CD10 positivity in molecular subtypes in her study[ 21 ]. This shows an association of CD10 positivity more in triple negative status. The study of Akmal et al.[ 22 ] showed positive correlation of stromal CD10 with respect to molecular subtypes. The variability in the results in various studies were likely due to the difference in the various technical factors and methodology, due to lack of standardization objective method of evaluation of Stromal CD10 unlike ER, PR, HER-2 which are well established in their evaluation methods along with the number of cases in the studies. The presence of TIL within the peri-tumoral stroma has been an important biomarker that reflects antitumor immune response in breast cancer[ 8 ]. Various studies have shown the prognostic and predictive significance of TIL to therapeutic responses in HER-2 positive and Triple-negative breast cancers[ 23 – 25 ]. We evaluated TIL in 30 cases of excision biopsy, as guidelines set by International TILs working group 2014. In the present study 53% of cases showed low TIL followed by 44% of intermediate TIL and 3% of high TIL. Similar results was seen in study of Karki et al.[ 27 ] Our study showed two cases of grade 3 tumors, followed by 12 cases of grade 2 tumor and 16 cases of grade 1 tumor. In grade 1 tumors low TIL was seen in 62.5% of cases (10 cases) and intermediate TIL was seen in 37.5% of cases (six cases). In grade 2 tumors low TIL was seen in 41.6% of cases (five case), intermediate TIL was seen in 50% of cases (six case) and high TIL was seen in 8.3% of cases (one case) as shown in Table 4 . There were only two cases of grade 3 tumor in which intermediate and low TIL was seen in 1:1 ratio (50% each). Our study showed predominance of Intermediate to high TIL in grade 2 tumors (58.34%) followed by grade 1 tumors (41.6%). Our study showed no statistical correlation of TIL with tumor grade. Similar results were found in studies done by Takada et al.[ 28 ] and Karki et al.[ 27 ] where intermediate to high TIL infiltrations was predominant in grade 2 tumors followed by grade 1. In contrast to the present study in the study conducted by Duong et al.[ 8 ] TIL expression was highest (64.5%) in grade 3 tumors as compared to grade 1 and grade 2 tumors. The discrepancy in the results might be due to the number of included cases, frequency of grade 3 tumors and lack of objective evaluation method of TIL. Present study showed highest number of Intermediate to High TIL expression (28.5% each) in HER-2, Triple-negative and Luminal A subtype. Luminal B subtype has shown only 15.3% of intermediate to high TILs. There was single case of high TIL and that was Triple-negative subtype as shown in table 7. In this study low TIL expression was most commonly seen in hormone receptor positive tumors compared to triple-negative and HER-2 positive tumors which is similar to the other studies[ 25 , 27 ]. The magnitude of TIL reflects the tumor-mutational burden, which is low in hormone receptor positive tumors compared to TNBC and HER-2 positive tumors[ 25 ]. A study by Duong et. al.[ 8 ] shows the presence of TIL within the peri-tumoral stroma has been an important biomarker that reflects antitumor immune response in breast cancer. Various studies have shown the prognostic and predictive significance of TIL to therapeutic responses in HER-2 positive and Triple-negative breast cancer[ 23 – 25 ]. Disis et. al.[ 23 ] have found that even a slight increase in stromal TIL surrounding the tumor has shown to predict the response to chemotherapy and overall survival in TNBCs and HER-2 positive breast cancers. The present study showed no statistical significance between TIL, histological grades and molecular subtypes of breast cancers. The insignificant correlation could be due to the smaller sample size and frequency of Triple-negative and HER-2 positive breast cancers. Therefore we could say that a larger sample size may have shown us findings more in line with some of the other studies. Conclusion This study was conducted to understand tumor microenvironment better by correlating TIL and Stromal CD10 expression in breast cancers with histological grade and molecular subtypes of breast cancer. CD10 expression was detected in almost one third of cases of cases. Similarly, Low TIL was detected in about half the cases followed by intermediate TIL in the remaining cases. We found no significant correlation between CD10 expression or TIL and the histological grades or molecular subtypes of breast cancer in our study. Abbreviations TIL Tumor Infiltrating lymphocytes IARC International Agency for Research on Cancer IHC Immunohistochemistry SPSS Statistical Package for Social Sciences CAP College of American Pathologists Declarations Ethical approval and consent to participate: An approval letter was obtained from the Institution Review Committee (IRC) of Institute of Medicine (IOM), Tribhuvan University on February 1 2022. Informed consent was taken from each participant for participation in the study. This study was performed in line with the principles of the Declaration of Helsinki. Consent for publication: Consent for publication was obtained along with the consent for participation in study. Availability of data and materials: The data and materials are available from the corresponding author on request. Competing interest: The authors declare that there is no competing interest. Funding: The authors have received no funding for the study or publication. Authors contribution: AB has worked on conceptualization, formulating methodology, investigation, formal analysis, and writing of the original draft. SS has worked on conceptualization, formulating methodology, investigation, formal analysis, and writing of the original draft, reviewing and editing of manuscript. AJ has worked on conceptualization, formulating methodology, formal analysis, review & editing of manuscript, and overall visualization of the project. Acknowledgements: Not applicable. Author information: No further information relevant. 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Tables Table 1: Summary of total cases included including tumor grade and molecular subtypes Core biopsy Mastectomy and lumpectomy Total Grade I 7 16 23 II 12 11 23 III 02 02 Molecular types Luminal A 6 09 15 Luminal B 07 04 11 HER-2 enriched 03 07 10 Triple negative 03 09 12 Table 2: Stromal CD10 staining according to histological grade CD10 immunostaining Histological Grade Total p- value 1 2 3 0.185 Positive 7 (30%) 7 (30%) 2 (100%) 16 Negative 16 (70%) 16 (70%) 0 (0%) 32 Total 23 (100%) 23 (100%) 2 (100%) 48 Table 3. Correlation of Stromal CD10 with Molecular subtypes Molecular subtypes CD10 Immunostaining Total p-value Positive Negative Luminal A 5 (33%) 10 (67%) 15 0.929 Luminal B 3 (27%) 8 (73%) 11 Triple-negative 5 (41%) 7 (59%) 12 HER-2 enriched 3 (30%) 7 (70%) 10 Total 16 32 48 Table 4: Correlation of TIL with histological grade TIL Histological Grade Total p- value 1 2 3 0.638 High 0 1 (100%) 0 1 Intermediate 6 (46%) 6 (46%) 1 (8%) 13 Low 10 (62%) 5 (31%) 1 (7%) 16 Total 16 12 2 30 Table 5: Correlation of TIL with molecular subtypes. Molecular subtypes TIL Total p-value Low Intermediate High Luminal A 5 (55%) 4 (45%) 0 (0%) 9 0.973 Luminal B 3 (60%) 2 (40%) 0 (0%) 5 Triple-negative 5 (55%) 3 (34%) 1 (11%) 9 HER-2 enriched 3 (42%) 4 (58%) 0 (0%) 7 Total 16 (53.3%) 13 (43.3%) 1 (3.4%) 30 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8591422","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":593394179,"identity":"55d8dcb8-c5da-4cb0-a907-7e0eee7d5d1e","order_by":0,"name":"Alina Basnet","email":"","orcid":"","institution":"Koshi Hospital","correspondingAuthor":false,"prefix":"","firstName":"Alina","middleName":"","lastName":"Basnet","suffix":""},{"id":593394180,"identity":"7802f3e2-7df0-440f-a37c-655357d108ab","order_by":1,"name":"Shreya Shrivastav","email":"data:image/png;base64,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","orcid":"","institution":"Maharajgunj Medical Camus, Institute of Medicine, Tribhuvan University","correspondingAuthor":true,"prefix":"","firstName":"Shreya","middleName":"","lastName":"Shrivastav","suffix":""},{"id":593394181,"identity":"26cd2119-7d52-4376-abf6-3151bd331b40","order_by":2,"name":"Abhimanyu Jha","email":"","orcid":"","institution":"Maharajgunj Medical Camus, Institute of Medicine, Tribhuvan University","correspondingAuthor":false,"prefix":"","firstName":"Abhimanyu","middleName":"","lastName":"Jha","suffix":""}],"badges":[],"createdAt":"2026-01-13 11:38:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8591422/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8591422/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103505257,"identity":"e004a7b6-ac7f-4f55-a525-d6f7c5514fe9","added_by":"auto","created_at":"2026-02-26 13:29:04","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":58889,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAge distribution of patients with breast carcinoma.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8591422/v1/0e190781a96776d0cb3e3372.jpg"},{"id":103177201,"identity":"31439818-9f80-43f1-aecf-cb2ea57b094b","added_by":"auto","created_at":"2026-02-22 16:47:26","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":62589,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFrequency of expression of CD10.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8591422/v1/febdb2bf4608edc95d7f95b6.jpg"},{"id":103177199,"identity":"028aac74-c7c9-443f-9960-53c655bd8baf","added_by":"auto","created_at":"2026-02-22 16:47:26","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":46465,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAssessment of TIL\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8591422/v1/8297336d0e965ca8269ca797.jpg"},{"id":103177202,"identity":"72b034a6-a5c9-4cd3-9908-cca3b4444ce9","added_by":"auto","created_at":"2026-02-22 16:47:27","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":279786,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Immunohistochemistry showing negative immunostaining for stromal CD10, magnification x200; (b) IHC with CD10 showing cytoplasmic positivity in 10-30% of stromal cells, magnification x200; (c) IHC showing \u0026gt;30% stromal positivity for CD10, magnification x200; (d) H and E stain showing tumor infiltrating lymphocytes (0-10%, low), magnification x200; (e) H and E stain showing Tumor infiltrating lymphocytes (20-40%, intermediate); (f) H and E stain showing Tumor infiltrating lymphocytes (50-90%, high).\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8591422/v1/3aeaf85885c9c139a0d78f68.jpg"},{"id":105269337,"identity":"a747a966-f542-4fb2-a600-00054dfd6284","added_by":"auto","created_at":"2026-03-24 08:12:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1384210,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8591422/v1/4da337c7-f11f-4c1d-9d9a-9e13851c256d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A study of microenvironment in invasive breast cancer-Tumor infiltrating lymphocytes and Stromal CD10 do not correlate with tumor grade and molecular subtypes","fulltext":[{"header":"Background","content":"\u003cp\u003eBreast cancer is the most common cancer globally. In Nepal, it is the third most common cancer overall and second most common cancer among women after cervix, according to statistics released by International Agency for Research on Cancer (IARC) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] in December 2020. The most important risk factor to breast carcinoma are gender, age, hormones levels and family history. One third of breast cancer occurs due to mutation of tumor suppressor genes in BRCA1 and BRCA2 with family history. The prognosis of breast carcinoma depends upon stage, histological grade, lymph node status, ER/PR and HER2-neu status. An additional factor that is associated with prognosis includes Tumor microenvironment. Although breast cancer is an epithelial carcinoma of terminal ductal lobular unit the stromal microenvironment plays an important role in its evolution and metastasis. Tumor-Infiltrating Lymphocytes (TIL) have been emerging as important prognostic marker as different studies have indicated that it has been strongly associated with some specific types of breast cancer[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. CD10 is a common acute lymphoblastic leukemia antigen which is zinc dependent metalloprotease and is normally expressed in epithelial cells[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Expression of stromal CD10 is associated with aggressive breast cancer[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. As, the incidence of breast carcinoma is increasing, the relation of tumor with tumor microenvironment is currently under research as it can help in determining the prognostic and predictive evaluation of the tumor[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e"},{"header":"Materials","content":"\u003cp\u003eThis is an analytical and cross-sectional study conducted from February 3, 2021, to February 2, 2022. A total of 8686 biopsies and resection specimens were received in the Department of Pathology, Tribhuvan University Teaching Hospital, Nepal. A total 80 cases (0.9%) core needle biopsies and excision biopsy specimens were received and morphologically diagnosed as Invasive Breast Carcinoma. Cases for which an both core biopsy and excisional biopsy were available, only the excisional biopsy was included. Eighteen cases that had undergone neo-adjuvant chemotherapy and 2 cases with scanty material were excluded with a final sample size of 48. Age, sex and laterality of the specimens were recorded. Histopathological examination, grading and staging were done. Immunohistochemistry for molecular typing was performed. Additional Immunohistochemistry (IHC) for CD10 done. CD 10 and TILs expression in relation to histological grade, Intrinsic molecular subtype was determined. The Statistical analysis for this study was done using the software IBM Statistical Package for social science (SPSS) version 25. The correlation between Tumor Infiltrating Lymphocytes and stromal CD10 histopathological grade and intrinsic molecular subtypes was made and strength of association was calculated by Fishers exact test and p value less than 0.05 are considered statistically significant.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eInterpretation and scoring system\u003c/h2\u003e \u003cp\u003eIHC for ER, PR and HER2 were scored according to CAP protocol 2019.\u003c/p\u003e \u003cp\u003eCD10: CD10 expression was evaluated in stroma around breast cancer. More than 10% expression in stromal cells was considered to be positive.\u003c/p\u003e \u003cp\u003eTumor infiltrative lymphocytes (TILS): Percentage of TILs were evaluated only of resection specimen, and classified as 0\u0026ndash;10% (Low), 20\u0026ndash;40% (Intermediate) and 50\u0026ndash;90%(High) as per the evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period between February 2022 to February 2023, of all biopsies received in Tribhuvan University Teaching Hospital, there were total of 80 cases (0.9%) diagnosed as invasive breast carcinoma. After application of the inclusion and exclusion criteria, total 48 cases were included in the study. All of the cases were female.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe age of the patients ranged from 30 to 79 years with a mean age of 52 years. The highest number of cases were in the range of 50-59years (29%). The youngest age of presentation was 30 years. The age distribution of the cases is shown in figure 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe right breast was affected more frequently than the left breast with 60% cases occurring in the right breast. There were no cases of bilateral carcinoma.\u003c/p\u003e\n\u003cp\u003eThe commonest histological subtype in this study is Invasive Ductal Carcinoma \u0026ndash;No Special Type which constituted 44 cases (92%) and other subtypes were two cases of mucinous carcinoma (4%), one case of metaplastic carcinoma (2%) and one case of invasive lobular carcinoma (2%).\u003c/p\u003e\n\u003cp\u003eTable 1shows the distribution of cases according to grade and according to molecular subtypes among core biopsy specimens and among mastectomy and lumpectomy specimens.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults for Expression of CD10:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTotal 16 cases were positive for Stromal CD10 (33%) and 32 cases were negative (67%) as shown if figure 2. The expression of CD10 is shown in detail in Table1.\u003c/p\u003e\n\u003cp\u003eAll the cases of Grade 3 tumor were positive whereas, only 30% of grade 1 and grade 2 tumors were positive for CD10. However, CD10 staining is not statistically significant with histological grade (\u003cem\u003ep- value\u003c/em\u003e0.185) as shown in Table 2.\u003c/p\u003e\n\u003cp\u003eTriple negative cases showed highest percentage of cases with CD10 positivity (41%) followed by luminal A (33%).There is no statistical correlation between CD10 expression and molecular subtypes (\u003cem\u003ep-value\u0026nbsp;\u003c/em\u003e0.929) as shown in table 3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult for Tumor infiltrating lymphocytes.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTIL was evaluated according to International TILs Working group (2014), which recommends full sections over core biopsies. Therefore only the thirty cases of excisional specimens were included in evaluation of TIL and core biopsies were excluded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTIL was assessed as low, intermediate and high based upon the International TILs Working group. Fifty three percent cases showed low TIL,44% cases showed intermediate TIL and 3% cases showed high TIL (Figure 3).\u003c/p\u003e\n\u003cp\u003eSixteen of total thirty (53%) showed low TIL which was most common in grade 1 tumor followed by grade 2. Out of 13 cases of (44%) intermediate TIL expression, equal TIL expression was seen in grade1 and grade 2 tumors. High TIL was expressed only in 1 case of grade 2 tumor and not in any of the Grade I and Grade III tumors as shown in table 4.\u003c/p\u003e\n\u003cp\u003eIntermediate-high TIL expression was highest in Luminal A, Triple- negative and HER-2 enriched subtype constituting four cases each. High TIL was seen only in one case with Triple-negative subtype.\u003c/p\u003e\n\u003cp\u003eFigure 4 shows representative photomicrographs of different CD10 staining and variable degrees of TIL.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe evolution of breast cancer is poorly understood due to its heterogeneity. The major cause is due to multiple genetic changes affecting numerous genes. Tumor microenvironment which constitutes fibroblasts, myofibroblasts, mesenchymal stem cells, adipocytes, tumor-infiltrating lymphocytes and endothelial cells facilitates development and progression of cancer.\u003c/p\u003e \u003cp\u003eForty eight cases of invasive breast carcinoma were included in the present study. Majority of patients were 40\u0026ndash;60 years of age (77%) with a mean of 52 years. The youngest age of presentation was 30 years. This was similar to studies conducted by Kandamuthan et al.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], Thapa. et al.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and Duong et al.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] However, the age of presentation is much older in some countries including the USA as shown in a survey between 2018\u0026ndash;2022[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In most studies, left breast was the more common side involved by breast carcinoma[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, our study revealed right breast as the commonest side (60%) involved by the cancer. Although breast cancer can occur in male breast, in present study all the cases were female[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCD10 which is expressed in stromal cells is associated with the aggressiveness of breast cancer[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Various studies have revealed CD10 expression is associated with higher histological grade and frequency of CD10 expression is higher in TNBCs[\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In our study, we used scoring system for CD10 based on Iwaya et al. where more than 10% of the stromal cells around breast cancer cells is considered positive for CD10[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Our study showed stromal CD10 positivity only in 16 cases (33%) with 67% of cases being negative for CD10. This was similar to the findings of a study done by Iwaya et al.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] in which CD10 positivity was 18%. However studies done by Raziq et al.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], Puri et al.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], Marketsov et al.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] revealed much higher CD10 positivity of 56%, 80% and 79% respectively. In our study two cases (100%) of grade 3 tumors, seven cases (30%) of grade 2 tumors and seven cases (30%) of grade 1 tumors showed CD10 positivity. Seventy percent of grade 1 tumor and grade 2 tumor each were CD10 negative. Statistical correlation between CD10 and grade (\u003cem\u003ep-value\u003c/em\u003e 0.185) was not found. This was similar to the findings of the study done by Puri et al.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], Sharma et al.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], Raziq et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] which showed no correlation of tumor grade with CD10. The findings are contradictory to those found in study byMakestov et al.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] where significant correlation was found between stromal CD10 positivity and increasing tumor grade. The discrepancy in stromal CD10 expression and tumor grade could be because higher number of cases included in their studies, which was four hundred thirty eight.\u003c/p\u003e \u003cp\u003eIn their studies number of grade 3 tumor were higher as compared to our study (2 cases). In contrast to various studies, our study showed 30% CD10 positivity in grade 1 tumor as well. In the present study Triple negative cases showed highest frequency of CD10 positivity (41%) followed by luminal A (33%), HER-2 enriched (30%) and Luminal B (27%) subtype. Luminal B subtype showed most CD10 negativity (73%). There was no statistical correlation between CD10 expression and molecular subtypes (\u003cem\u003ep-value\u003c/em\u003e 0.929) as shown in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Our finding is similar to the study of Louhichi et al.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] Louchichi et al. revealed stromal CD10 expression in 24.3% of Triple-negative tumors, 31.2% of HER-2 enriched, 14% of Luminal A and 3% of Luminal B tumors. A study by Livasy et al. revealed CD10 stromal positivity in fewer cases, i.e.11% of Triple-negative cases and 8% of HER-2 enriched. There was no Stromal CD10 positivity in molecular subtypes in her study[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. This shows an association of CD10 positivity more in triple negative status. The study of Akmal et al.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] showed positive correlation of stromal CD10 with respect to molecular subtypes. The variability in the results in various studies were likely due to the difference in the various technical factors and methodology, due to lack of standardization objective method of evaluation of Stromal CD10 unlike ER, PR, HER-2 which are well established in their evaluation methods along with the number of cases in the studies. The presence of TIL within the peri-tumoral stroma has been an important biomarker that reflects antitumor immune response in breast cancer[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Various studies have shown the prognostic and predictive significance of TIL to therapeutic responses in HER-2 positive and Triple-negative breast cancers[\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. We evaluated TIL in 30 cases of excision biopsy, as guidelines set by International TILs working group 2014. In the present study 53% of cases showed low TIL followed by 44% of intermediate TIL and 3% of high TIL. Similar results was seen in study of Karki et al.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] Our study showed two cases of grade 3 tumors, followed by 12 cases of grade 2 tumor and 16 cases of grade 1 tumor. In grade 1 tumors low TIL was seen in 62.5% of cases (10 cases) and intermediate TIL was seen in 37.5% of cases (six cases). In grade 2 tumors low TIL was seen in 41.6% of cases (five case), intermediate TIL was seen in 50% of cases (six case) and high TIL was seen in 8.3% of cases (one case) as shown in Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. There were only two cases of grade 3 tumor in which intermediate and low TIL was seen in 1:1 ratio (50% each). Our study showed predominance of Intermediate to high TIL in grade 2 tumors (58.34%) followed by grade 1 tumors (41.6%). Our study showed no statistical correlation of TIL with tumor grade. Similar results were found in studies done by Takada et al.[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and Karki et al.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] where intermediate to high TIL infiltrations was predominant in grade 2 tumors followed by grade 1. In contrast to the present study in the study conducted by Duong et al.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] TIL expression was highest (64.5%) in grade 3 tumors as compared to grade 1 and grade 2 tumors. The discrepancy in the results might be due to the number of included cases, frequency of grade 3 tumors and lack of objective evaluation method of TIL. Present study showed highest number of Intermediate to High TIL expression (28.5% each) in HER-2, Triple-negative and Luminal A subtype. Luminal B subtype has shown only 15.3% of intermediate to high TILs. There was single case of high TIL and that was Triple-negative subtype as shown in table 7. In this study low TIL expression was most commonly seen in hormone receptor positive tumors compared to triple-negative and HER-2 positive tumors which is similar to the other studies[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The magnitude of TIL reflects the tumor-mutational burden, which is low in hormone receptor positive tumors compared to TNBC and HER-2 positive tumors[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. A study by Duong et. al.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] shows the presence of TIL within the peri-tumoral stroma has been an important biomarker that reflects antitumor immune response in breast cancer. Various studies have shown the prognostic and predictive significance of TIL to therapeutic responses in HER-2 positive and Triple-negative breast cancer[\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Disis et. al.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] have found that even a slight increase in stromal TIL surrounding the tumor has shown to predict the response to chemotherapy and overall survival in TNBCs and HER-2 positive breast cancers. The present study showed no statistical significance between TIL, histological grades and molecular subtypes of breast cancers. The insignificant correlation could be due to the smaller sample size and frequency of Triple-negative and HER-2 positive breast cancers.\u003c/p\u003e \u003cp\u003eTherefore we could say that a larger sample size may have shown us findings more in line with some of the other studies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study was conducted to understand tumor microenvironment better by correlating TIL and Stromal CD10 expression in breast cancers with histological grade and molecular subtypes of breast cancer. CD10 expression was detected in almost one third of cases of cases. Similarly, Low TIL was detected in about half the cases followed by intermediate TIL in the remaining cases. We found no significant correlation between CD10 expression or TIL and the histological grades or molecular subtypes of breast cancer in our study.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTIL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTumor Infiltrating lymphocytes\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIARC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Agency for Research on Cancer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eImmunohistochemistry\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSPSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStatistical Package for Social Sciences\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCAP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCollege of American Pathologists\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate:\u003c/strong\u003e An approval letter was obtained from the Institution Review Committee (IRC) of Institute of Medicine (IOM), Tribhuvan University on February 1 2022. Informed consent was taken from each participant for participation in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Consent for publication was obtained along with the consent for participation in study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The data and materials are available from the corresponding author on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest:\u003c/strong\u003e The authors declare that there is no competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The authors have received no funding for the study or publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contribution:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eAB has worked on\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003econceptualization, formulating methodology, investigation, formal analysis, and writing of the original draft.\u003c/p\u003e\n\u003cp\u003eSS has worked on\u0026nbsp;conceptualization, formulating methodology, investigation, formal analysis, and writing of the original draft, reviewing and editing of manuscript.\u003c/p\u003e\n\u003cp\u003eAJ has worked on conceptualization, formulating methodology, formal analysis, review \u0026amp; editing of manuscript, and overall visualization of the project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information:\u003c/strong\u003e No further information relevant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have received no external funding and the research is self-financed.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organization. Breast cancer now most common form of cancer: \u003cem\u003eWHO taking action\u003c/em\u003e. Geneva; WHO;2021 Feb 3 [cited 2022 Jan 13]. Available from: https://www.who.int/news/item/03-02-2021-breast-cancer-now-most-common-form-of-cancer-who-taking-action\u003c/li\u003e\n\u003cli\u003eDenkert C, von Minckwitz G, Darb-Esfahani S, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40-50. doi:10.1016/S1470-2045(17)30904-X\u003c/li\u003e\n\u003cli\u003eDhande AN, Sinai Khandeparkar SG, Joshi AR, et al. Stromal expression of CD10 in breast carcinoma and its correlation with clinicopathological parameters. South Asian J Cancer. 2019;8(1):18-21. doi:10.4103/sajc.sajc_56_18\u003c/li\u003e\n\u003cli\u003ePuri V, Jain M, Thomas S. Stromal Expression of CD10 in Invasive Breast Carcinoma and Its Correlation with ER, PR, HER2-neu, and Ki67. Int J Breast Cancer. 2011;2011:437957. doi:10.4061/2011/437957\u003c/li\u003e\n\u003cli\u003eKamarudin NA, Abd Shukor N, Farouk WI, Muhammad Hanapi NA, Mohammed F. Stromal expression of CD10 in invasive breast carcinoma and its association with tumour stage, grade, ER, PR and HER2 status. Malays J Pathol. 2021;43(3):389-396.\u003c/li\u003e\n\u003cli\u003eKandamuthan S, Thambi R. Role of CD10 as a Prognostic Marker in Invasive Breast Carcinoma. \u003cem\u003eJournal of Clinical and Diagnostic Research\u003c/em\u003e\u003cem\u003e \u003c/em\u003e2022;16. \u003c/li\u003e\n\u003cli\u003eThapa B, Singh Y, Sayami P, Shrestha UK, Sapkota R, Sayami G. Breast cancer in young women from a low risk population in Nepal. Asian Pac J Cancer Prev. 2013;14(9):5095-5099. doi:10.7314/apjcp.2013.14.9.5095\u003c/li\u003e\n\u003cli\u003eDuong TT, Pham DTN, Duong HNT, Ly TT, Thai TA. Stromal tumor-infiltrating lymphocytes associated with immunohistopathology and molecular subtypes of breast cancer in Vietnam. Asian Pac J Cancer Prev. 2023 Jul 1;24(7):2523\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eSurveillance Research Program, National Cancer Institute. SEER*Explorer. Breast cancer- Breast cancer median age at diagnosis 2018-2022, by race/ethnicity, female. Accessed on April 16, 2025. https://seer.cancer.gov/explorer/, 2025.\u003c/li\u003e\n\u003cli\u003eAl Saad S, Al Shenawi H, Almarabheh A, Al Shenawi N, Mohamed AI, Yaghan R. Is laterality in breast Cancer still worth studying? Local experience in Bahrain. BMC Cancer. 2022;22(1):968. Published 2022 Sep 10. doi:10.1186/s12885-022-10063-y\u003c/li\u003e\n\u003cli\u003eNepal Health Research Council (NHRC). Progress-Interim-_cancer.pdf. Kathmandu: NHRC; 2019Apr [cited 2023 Oct 5]. Available from: https://nhrc.gov.np/wp-content/uploads/2019/04/Progress-Interim-_cancer.pdf\u003c/li\u003e\n\u003cli\u003eHowlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5):dju055. Published 2014 Apr 28. doi:10.1093/jnci/dju055\u003c/li\u003e\n\u003cli\u003e. Makretsov NA, Hayes M, Carter BA, Dabiri S, Gilks CB, Huntsman DG. Stromal CD10 expression in invasive breast carcinoma correlates with poor prognosis, estrogen receptor negativity, and high grade. Mod Pathol. 2007;20(1):84-89. doi:10.1038/modpathol.3800713\u003c/li\u003e\n\u003cli\u003eJana SH, Jha BM, Patel C, Jana D, Agarwal A. CD10-A new prognostic stromal marker in breast carcinoma, its utility, limitations and role in breast cancer pathogenesis. Indian Journal of Pathology and Microbiology. 2014 Oct 1;57(4):530. \u003c/li\u003e\n\u003cli\u003eB. V. Anuradha Devi, S. Chandra Sekhar, C. Saritha, S. Sanhya Anil, H. Sandhya Rani. A study on stromal CD10 expression in invasive breast carcinoma. Asian Pacific journal Of cancer biology. 2016; 3(6): 142-147.\u003c/li\u003e\n\u003cli\u003eIwaya K, Ogawa H, Izumi M, Kuroda M, Mukai K. Stromal expression of CD10 in invasive breast carcinoma: a new predictor of clinical outcome. Virchows Arch. 2002;440(6):589-593. doi:10.1007/s00428-002-0639-4\u003c/li\u003e\n\u003cli\u003eRaziq AH, Masoud SM. The correlation of stromal CD10 expression in invasive breast cancer with various clinicopathological parameters. Journal of the Faculty of Medicine Baghdad. 2022;64(2):83-87. \u003c/li\u003e\n\u003cli\u003ePuri V, Jain M, Thomas S. Stromal Expression of CD10 in Invasive Breast Carcinoma and Its Correlation with ER, PR, HER2-neu, and Ki67. Int J Breast Cancer. 2011;2011:437957. doi:10.4061/2011/437957.\u003c/li\u003e\n\u003cli\u003eSharma I, Singh A. Association of CD10 expression in breast cancer: A prospective analysis. International Journal of Current Science. 2022;12(1):336-341.\u003c/li\u003e\n\u003cli\u003eLouhichi T, Saad H, Dhiab MB, Ziadi S, Trimeche M. Stromal CD10 expression in breast cancer correlates with tumor invasion and cancer stem cell phenotype. BMC Cancer. 2018;18(1):49. Published 2018 Jan 6. doi:10.1186/s12885-017-3951-8\u003c/li\u003e\n\u003cli\u003eLivasy CA, Karaca G, Nanda R, et al. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. \u003cem\u003eMod Pathol\u003c/em\u003e. 2006;19(2):264-271. doi:10.1038/modpathol.3800528\u003c/li\u003e\n\u003cli\u003eKamarudin NA, Abd Shukor N, Farouk WI, Muhammad Hanapi NA, Mohammed F. Stromal expression of CD10 in invasive breast carcinoma and its association with tumour stage, grade, ER, PR and HER2 status. Malays J Pathol. 2021;43(3):389-396.\u003c/li\u003e\n\u003cli\u003eStanton SE, Disis ML. Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer. 2016;4:59. Published 2016 Oct 18. doi:10.1186/s40425-016-0165-6\u003c/li\u003e\n\u003cli\u003eDenkert C, von Minckwitz G, Darb-Esfahani S, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40-50. doi:10.1016/S1470-2045(17)30904-X.\u003c/li\u003e\n\u003cli\u003eEl Bairi K, Haynes HR, Blackley E, Fineberg S, Shear J, Turner S, et al. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group. npj Breast Cancer. 2021 Dec 1;7(1):1\u0026ndash;17. \u003c/li\u003e\n\u003cli\u003eSalgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Annals of Oncology. 2015 Feb;26(2):259\u0026ndash;71. \u003c/li\u003e\n\u003cli\u003eKarki S, Tiwari S, Basnet A. Evaluation of tumor infiltrating lymphocytes in breast carcinomas. Journal of Pathology of Nepal. 2022 Sep 30;12:1909\u0026ndash;12. \u003c/li\u003e\n\u003cli\u003eTakada K, Kashiwagi S, Asano Y, Goto W, Kouhashi R, Yabumoto A, et al. Prediction of lymph node metastasis by tumor-infiltrating lymphocytes in T1 breast cancer. BMC Cancer. 2020 Jun 26;20(1):598. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: Summary of total cases included including tumor grade and molecular subtypes\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eCore biopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003eMastectomy and lumpectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMolecular types\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eLuminal A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eLuminal B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eHER-2 enriched\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eTriple negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Stromal CD10 staining according to histological grade\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"564\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCD10 immunostaining\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 286px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistological Grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep- value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.185\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePositive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e7 (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e7 (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e2 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNegative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e16 (70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e16 (70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e23 (100%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e23 (100%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2 (100%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e48\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Correlation of Stromal CD10 with Molecular subtypes\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"564\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMolecular subtypes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 295px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD10 Immunostaining\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePositive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNegative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLuminal A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e5 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e10 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.929\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLuminal B\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e3 (27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e8 (73%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTriple-negative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e5 (41%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e7 (59%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHER-2 enriched\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e3 (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e7 (70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4: Correlation of TIL with histological grade\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"576\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTIL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 294px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Histological Grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep- value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.638\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntermediate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e6 (46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6 (46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e13\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLow\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e10 (62%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e5 (31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e16\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e30\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5: Correlation of TIL with molecular subtypes.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"635\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMolecular subtypes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 287px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTIL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLow\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntermediate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLuminal A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e5 (55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e4 (45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.973\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLuminal B\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e3 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e2 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTriple-negative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e5 (55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e3 (34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e1 (11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHER-2 enriched\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e3 (42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e4 (58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e16 (53.3%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e13 (43.3%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 (3.4%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e30\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Breast carcinoma, CD10, tumor microenvironment, Tumor-infiltrating lymphocytes","lastPublishedDoi":"10.21203/rs.3.rs-8591422/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8591422/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBreast cancer is the second most common cancer among women worldwide. Tumor microenvironment which constitutes fibroblasts, myofibroblasts, mesenchymal stem cells, adipocytes, tumor-infiltrating lymphocytes (TILs) and endothelial cells facilitates progression and development of cancer. CD10 which is expressed in the stromal cells is thought to be associated with the aggressiveness of breast cancer. The presence of TILs within the peritumoral stroma is an important biomarker that \u0026nbsp;reflects antitumor immune response in breast cancer especially in HER-2 positive and Triple-negative breast cancers.\u003c/p\u003e\n\u003cp\u003eMethods\u003c/p\u003e\n\u003cp\u003eThe study was undertaken with the objective to evaluate expression of Tumor Infiltrating lymphocytes and Stromal CD10 in Breast carcinoma.\u003c/p\u003e\n\u003cp\u003eThis was an analytical and cross-sectional study conducted from February 3, 2021, to February 2, 2022. Forty eight cases including core biopsies, excisional biopsies and mastectomies were evaluated for Stromal CD10 and 30 excisional biopsies were evaluated for TIL. Age, sex and laterality of the specimens were recorded. CD10 and TILs expression was determined in relation to histological grade and intrinsic molecular subtype.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eForty eight cases of invasive breast carcinoma were studied. Total 16 cases were positive for stromal CD10 (33%). All the cases of grade 3 tumor were stromal CD10 positive. Triple negative cases showed highest frequency of cases with CD10 positivity (41%). TIL was evaluated only in 30 of the cases, as they were resection specimens, according to International TIL Working group 2014. Sixteen of these cases (53%) showed low TIL which was most common in grade 1 tumor followed by grade 2. TIL expression was high to intermediate most frequently in Triple-negative, HER-2 enriched and Luminal A subtypes constituting four cases each.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCD10 expression was detected in almost one third of cases of which expression was highest in Triple negative breast cancers and was 100% in grade 3 tumors. Low TIL was detected in about 53% of cases followed by intermediate TIL in 44% of cases. High to intermediate TIL was seen in Triple-negative breast cancers and HER-2 enriched tumors most frequently.\u003c/p\u003e","manuscriptTitle":"A study of microenvironment in invasive breast cancer-Tumor infiltrating lymphocytes and Stromal CD10 do not correlate with tumor grade and molecular subtypes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-22 16:47:22","doi":"10.21203/rs.3.rs-8591422/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4efdc9dd-ba4c-4e01-824f-f5ce2194488f","owner":[],"postedDate":"February 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-24T08:10:59+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-22 16:47:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8591422","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8591422","identity":"rs-8591422","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}