Clinical and Prognostic Characteristics of 40 Cases of INI1-deficient Tumor in Children. A Single-Institute Experience from 2012 to 2022

Clinical and Prognostic Characteristics of 40 Cases of INI1-deficient Tumor in Children. A Single-Institute Experience from 2012 to 2022 | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical and Prognostic Characteristics of 40 Cases of INI1-deficient Tumor in Children. A Single-Institute Experience from 2012 to 2022 Shihan Zhang, Xisi Wang, Dawei Zhang, Huanmin Wang, Ming Ge, Libing Fu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4092439/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 This study aims to summarize the clinical features and prognoses of INI1-deficient tumors in children. It further aims to analyze the high-risk factors affecting INI1-deficient tumors prognosis. Methods Clinical data from 40 children with INI1-deficient tumors treated in Beijing Children’s Hospital from January 2012 to December 2022, along with the high-risk factors affecting prognosis, were retrospectively analyzed. Results Forty patients were diagnosed with INI1-deficient tumor at a median age of 32.5 months, including 31cases of malignant rhabdoid tumor, 4 cases of epithelioid sarcoma, 3 cases of malignant peripheral nerve sheath tumor, 1case of soft tissue myoepithelial carcinoma and 1 case of small cell carcinoma of the ovary with hypercalcemia. Thirteen patients(13/40, 32.5%) had metastases at diagnosis. Among the 40 patients, 21 patients died, including 6 patients with MRTK, 9 patients with EERT, 5 patients with AT/RT and 1 patients with SCCOHT. The overall survival rates of 1 years and 3 years for the entire cohort were 53.8%±8.0% and 43.6%±8.6% respectively. After survival analysis, it was clear that malignant rhabdoid tumor, lung metastasis and ki 67>60% had relatively poor outcomes. Lung metastasis was an independent risk factor for the prognosis of INI1-deficient tumor. Conclusion INI1-deficient tumor is a highly aggressive tumor in children especially with lung metastasis. Much work should do to improve the outcomes and survival for patients with aggressive INI1-deficient tumors. INI1-deficient tumors Children Prognostic analysis Single-Institute Background SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), also known as integrase interactor 1 (INI1), is a crucial component of a chromatin-remodeling protein complex [ 1 ] . INI1 acts as a tumor suppressor gene, and loss-of-function alterations due to various genetic and/or epigenetic abnormalities give rise to INI1-deficient tumors [ 2 ] . In 1998, somatic alterations, mainly deletions, in the INI1 gene accompanying loss of expression were identified as a molecular marker of malignant rhabdoid tumors (MRTs) [ 3 ] . Since then, INI1 gene inactivation or loss of expression has been observed in a group of malignancies collectively defined as INI1-deficient tumors [ 4 ] . The prototypical INI1-deficient tumor is malignant rhabdoid tumor, but numerous other tumor types with the complete loss of INI1 have been described such as epithelioid sarcoma(ES), malignant peripheral nerve sheath tumor(MPNST), almost all of which have a poor prognosis [ 5 ] . For further insight into INI1-deficient tumor, we reviewed all patients who had INI1-deficient tumor diagnosed and treated in our institution for the past 10 years. In this report, we describe their clinical characteristics, treatment schedules, clinical outcomes, and prognostic factors. Methods Patients The use of immunohistochemistry (IHC) have identified numerous other cancers with the depletion or loss of SMARCB1 [ 6 , 7 ] .A retrospective medical record review was conducted on 40 patients treated for INI1-deficient tumor in Beijing Children’s Hospital (BCH) between January 2012 to December 2022. All the patients were pathologically confirmed as INI1-deficient tumor by the institutional pathologist based on morphological and immunohistochemical (IHC) evaluations. The basic information of patients was collected by referring to their medical record: age, sex, clinical symptoms, imaging examination, primary tumor sites and metastatic sites, treatment schedules, IHC staining of INI1, and prognosis characteristics. All methods were carried out in accordance with relevant guidelines and regulations. Treatment Patients with INI1-deficient tumor were mainly treated with multimodal therapy based on surgery, chemotherapy, radiotherapy. Surgical procedures included biopsy, total resection, subtotal resection, Because of the lack of standardized treatment protocols forNI1-deficient tumor, there were various combinations of chemotherapeutic drugs in this study. The last follow-up was on Oct 30, 2023. Statistical Analysis Statistical analysis was performed by SPSS, version 19.0, for Windows (SPSS, Chicago, IL, USA). Continuous variables were presented by mean with standard deviation, or median and interquartile range if normality hypothesis test rejected the null hypothesis of normal distribution. Student’s t test or the Mann-Whitney U test was used for comparing variables between different subgroups. Univariate and multivariate Cox regression analyses were performed for all prognostic factors to screen out independent risk factors. Categorical variables were reported as counts and percentages and were studied using a chi-square test. For the time-to-event analysis, we estimated event-free survival (EFS) and OS with Kaplan-Meier curves. P < 0.05 was considered as statistically significant. Results Patients and Clinical Characteristics A total of 40 patients with INI1-deficient tumors were studied, including 31 with MRT (77.5%), 4 with ES (10.0%, two of them were proximal type), 3 with MPNST (7.5%), 1 with soft tissue myoepithelial carcinoma (2.5%) and 1 with small cell carcinoma of the ovary with hypercalcemia (2.5%). Twenty-one patients were male, and 19 were female, giving a male-to-female ratio of 1.26:1.The median age at presentation was 32.5 months (range, from 11 to 148 months). The median maximum diameters of primary tumors was 5.9cm (range, from 2.5to 21.1cm).Thirteen patients (13/40, 32.5%) had distant stage, including 12 patients had metastasis at the time of diagnosis and 1 patients had metastasis during treatment. The most common site of metastasis was the lung (7/40, 17.5%), other common sites included lymph nodes, liver, bones, and skin.The clinical characteristics are shown in Table 1 . Table 1 The clinical characteristics of patients with INI1-deficient tumor Clinical Characteristics N (%) Tumor Type MRTK EERT AT/RT ES MPNST MEC SCCOHT 9(22.5%) 17(42.5%) 5(12.5%) 4(10%) 3(7.5%) 1(2.5%) 1(2.5%) Gender Male Female 21(52.5%) 19(47.5%) Age ≥24 months <24 months 24(60.0%) 16(40.0%) Distant metastasis Lung Bone Liver Lymph nodes Skin 7(17.5%) 5(12.5%) 2(5.0%) 7(17.5%) 1(2.5%) Treatment Schedules There was no standardized treatment option for INI1-deficient tumors, but multimodal therapy was recommended. Treatment schedules are listed in Table 2 . Thirty-six patients received chemotherapy with a median cycle of 5 (1–14) cycles. Of the 17 cases of EERT,12 patients received tumor resection, including 7 cases of upfront resection and 5 cases of delayed surgery after chemotherapy. Four patient declined therapy after the biopsy or chemotherapy because of tumor rupture and tumor progression and one primary tumors were unresectable even after 6 cycles of induction chemotherapy. For the 9 cases of MRTK, all patients received resection, which included 8 cases of nephrectomy and 1 cases of nephron-sparing surgery. For the 5 cases of AT/RT, 4 patients received upfront resection. For the 3 cases of MPNST, 2patients received upfront resection and 1patient received delayed surgery. For the 4 cases of ES, all patients received upfront resection. Six of the 42 patients received radiation (two patients with MRTK, two with EERT, one with ES and one with AT/RT), and dose and extent of radiation varied upon the primary site and patients’ age. Table 2 Treatment schedules of patients with INI1-deficient tumor Treatment EERT N MRTK N ATRT N MPNST N ES N MEC N SCCOHT N Chemotherapy Yes No 16 1 8 1 3 2 3 0 4 0 1 0 1 0 Surgery Biospy Total resection 5 12 0 9 a 0 5 0 3 0 4 0 1 0 1 Radiotherapy Yes No 2 15 2 7 1 4 0 3 1 3 0 1 0 1 Outcome The EFS rates of 1 year and 3 years for the entire cohort were 51.3%±8.0% and 38.9%±8.3% respectively. The overall survival rates of 1 years and 3 years for the entire cohort were 53.8%±8.0% and 43.6%±8.6% respectively, and the median OS was 16 months.Tumor progression or recurrence occurred in 25 patients of the entire cohort. Most events (17/25 68%) occurred within 6 months (including 6 months), with a median time of 4 (0.5–39) months after diagnosis of INI1-deficient tumors. After a median follow up of 14 months (range 0.3–132.0), 21 patients died, including 6 patients with MRTK, 9 patients with EERT, 5 patients with AT/RT and 1 patients with SCCOHT. Among the 21 dead patients, 20 died from rapid disease progression or recurrence and 1 died from tumor rupture. Immunohistochemical characteristics All the children underwent postoperative histopathological immunohistochemical tests. Due to the large number of immunohistochemical items and the large differences between individuals, we listed the test items covering more than 60% of the children ( Table 3 ) . Univariate prognostic correlation analysis was performed on the above collected immunohistochemical data, and it was found that>60% of ki-67 positive areas were associated with poor prognosis (HR 2.75, 95%CI: 1.11–6.83; P = 0.03) ( Table 4 . ) Table 3 Immunohistochemistry of patients with INI1-deficient tumor Overall Alive Dead p N = 40 N = 19 N = 21 INI_1 (%) (-) 40 (100.0) 19 (100.0) 21 (100.0) NA EMA (%) (-) 5(15.6%) 2 (6.3%) 3(9.4%) 0.62 (+) 27 (84.4%) 14(43.8%) 13 (40.6%) Desmin (%) (-) 23(69.7%) 13 (39.4%) 10(30.3%) 0.16 (+) 10 (30.3%) 3 (9.1%) 7 (21.1%) Ki_67 >60% 18(47.4%) 4(10.5%) 14(36.8%) 0.008 ≤ 60% 20 (52.6%) 13 (34.2%) 7 (18.4%) CD34(%) (-) 12 (44.4%) 6(22.2%) 6(22.2%) 0.86 (+) 15 (55.6%) 8 (29.6%) 7(25.9%) Table 4 Univariate analysis of immunohistochemistry of patients with INI1-deficient tumor HR CI P INI_1 NA NA-NA NA CD34 1.024 0.343–3.055 0.966 EMA 0.782 0.223–2.748 0.702 Desmin 1.176 0.672–4.650 0.248 Ki_67 2.747 1.105–6.829 0.03 Prognostic factors After survival analysis, we found that survival was not impacted by the age, sex. and tumor diameter. Patients with INI1-deficient non-MRT tumors had a more favorable 3-year OS of 88.9%±10.5% vs. 30.3%±9.2% for those with INI1-deficient MRT( p < 0.01). Patients with lung metastasis had a worse prognosis than those without(3-year OS:0% vs. 50.4%±9.6%, p 60% of ki-67 positive areas had a worse prognosis than those without(3-year OS:20.8%±9.9% vs.63.2%±11.1%, p = 0.02). The children with with lung metastasis (HR 8.828, 95%CI: 2.245–34.711; P = 0.002) was an independent risk factor for the prognosis of INI1-deficient tumor. DISCUSSION Here, we have presented the systematic review of patient characteristics, treatment details, and survival outcomes of patients with INI1-deficient tumor. INI1is a member of a large protein complex involved in chromatin remodeling and thus regulation of gene expression [ 8 ] . INI1-deficient cancers are characterized by the biallelic loss of function in both INI1 alleles [ 5 ] . INI1 immunohistochemistry has emerged as a powerful diagnostic tool to identify INI1-altered neoplasms in routine surgical pathology practice [ 9 , 10 ] . INI1 deficiency is observed as the genetic hallmark in virtually all MRT and in most cases of ES and PDC. In addition, subsets of myoepithelial carcinoma, extraskeletal myxoid chondrosarcoma, and epithelioid peripheral nerve sheath tumors are INI1-deficient [ 7 , 11 ] . MRT, a rare tumor occurring almost exclusively in infants and young children, is caused by INI1 biallelic inactivation in virtually all cases [ 12 ] . MRT can occur in the kidney, central nervous system, or extracranial/extrarenal locations [ 10 ] . The tumors occur in infants and young children and confer a poor prognosis requiring aggressive therapeutic interventions to improve the chances for survival. In our study, patients with INI1-deficient non-MRT tumors had a more favorable 3-year OS of 88.9%±10.5% vs. 30.3%±9.2% for those with INI1-deficient MRT( p < 0.01). MRTs pose a diagnostic challenge, as they display heterogeneous histopathologic features and differentiate along multiple lineages. The identification of alterations in the INI1 gene in MRT using immunohistochemical staining has lead to improved diagnosis of MRT as well as the discovery of the loss of INI1 expression in some non-MRTs [ 13 ] . ES is a rare and aggressive soft-tissue sarcoma subtype, FISH analysis demonstrates INI1 genomic inactivation through homozygous deletion in 90% of epithelioid sarcomas [ 14 ] , along with INI1 loss in 90% of cases, irrespective of histologic subtype. This tumor is cytokeratin and EMA positive, which can be mistaken for myoepithelial carcinoma (MEC) of soft tissue, ES expresses positivity for CD34 but negativity for myoepithelial markers and S100 [ 15 ] . CD34 expression in > 50% of ES is helpful to rule out metastatic carcinoma and CD34 immunostaining can be helpful, as this marker is positive in about half of ES and is typically negative in MRTK in Proximal ES [ 16 ] . Some authors realized that diagnostic utility of INI1 in cases with the exclusive composition of epithelioid tumor cells with CD34 negativity [ 17 ] . (MEC) of soft tissue, also known as malignant myoepithelial tumor, is an uncommon malignancy. Cytologic diagnosis of this entity is challenging due to its rarity and heterogeneous morphology. Wang L et al reported a case with MEC of soft tissue showed loss of INI-1 expression [ 18 ] . PDC, a rare, aggressive tumor originating from notochordal tissue, shows loss of INI1 expression, which occurs in children and young adults, with a peak incidence at 1–29 years of age (median, 11 years) [ 19 ] , An overview of the gene expression profiles from a spectrum of connective tissue tumors suggested that brachyury was uniquely expressed in chordomas, and almost all cases of chordoma including conventional and PDC showed brachyury immunoexpression. Conclusions INI1-deficient tumor is a highly aggressive tumor in children. Lung metastasis was an independent risk factor. Future concerted efforts on more accurate and earlier diagnosis distinguishing from other entities of malignancies, multimodality management, and evaluation of novel therapies are compellingly needed to improve its treatment outcomes and survival. Abbreviations Abbreviation English name ATRT Sellar Atypical Teratoid/Rhabdoid Tumors EERT extrarenal extracranial rhabdoid tumor MRTK malignant rhabdoid tumor of the kidney MPNST Malignant Peripheral Nerve Sheath Tumors MEC Myoepithelial carcinoma N Number SCCOHT Small-cell carcinoma of the ovary, hypercalcemic type. Declarations Ethics approval and consent to participate Ethics approval and consent to participate Patients and their parents provided written informed consent for the study. This study was performed in line with the principles of the Declaration of Helsinki. Approved by the Ethics Committee of Beijing Children’s Hospital, Capital Medical University (number：2018-k-106) Consent for publication The consent of the child and their parents or legal guardians has been obtained. Availability of data and materials: The data that support the findings of this study are available from Beijing Children’s Hospital but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Beijing Children’s Hospital. Conflict of interest The authors have no relevant financial or non-financial interests to disclose. Funding The article was supported by Beijing Natural Science Foundation (No.7222054) and Beijing Research Ward Project (BCRW202101). Author contributions YS and XLM designed the study, SHZ, XSW, DWZ, collected the data, HMW, MG were involved in data cleaning, mortality follow-up, LBF, TY analyzed the data. SHZ drafted the manuscript, YS contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. All authors have read and approved the final manuscript. Acknowledgements All authors would like to thank the participating patients and their families. References Kohashi K, Oda Y. Oncogenic roles of SMARCB1/INI1 and its deficient tumors. Cancer Sci. 2017;108(4):547–52. Agaimy A. SWI/SNF Complex-Deficient Soft Tissue Neoplasms: A Pattern-Based Approach to Diagnosis and Differential Diagnosis. Surg Pathol Clin. 2019;12(1):149–63. Versteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;394(6689):203–6. Duan Z, Yao K, Yang S, Qu Y, Ren M, Zhang Y, et al. Primary adult sellar SMARCB1/INI1-deficient tumor represents a subtype of atypical teratoid/rhabdoid tumor. Mod Pathol. 2022;35(12):1910–20. Cooper GW, Hong AL. SMARCB1-Deficient Cancers: Novel Molecular Insights and Therapeutic Vulnerabilities. Cancers (Basel). 2022;14(15). Cheng JX, Tretiakova M, Gong C, Mandal S, Krausz T, Taxy JB. Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior. Mod Pathol. 2008;21(6):647–52. Sullivan LM, Folpe AL, Pawel BR, Judkins AR, Biegel JA. Epithelioid sarcoma is associated with a high percentage of SMARCB1 deletions. Mod Pathol. 2013;26(3):385–92. Peterson CL, Dingwall A, Scott MP. Five SWI/SNF gene products are components of a large multisubunit complex required for transcriptional enhancement. Proc Natl Acad Sci U S A. 1994;91(8):2905–8. Judkins AR. Immunohistochemistry of INI1 expression: a new tool for old challenges in CNS and soft tissue pathology. Adv Anat Pathol. 2007;14(5):335–9. Hollmann TJ, Hornick JL. INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol. 2011;35(10):e47–63. Cha YJ, Hong CK, Kim DS, Lee SK, Park HJ, Kim SH. Poorly differentiated chordoma with loss of SMARCB1/INI1 expression in pediatric patients: A report of two cases and review of the literature. Neuropathology. 2018;38(1):47–53. Eaton KW, Tooke LS, Wainwright LM, Judkins AR, Biegel JA. Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. Pediatr Blood Cancer. 2011;56(1):7–15. Margol AS, Judkins AR. Pathology and diagnosis of SMARCB1-deficient tumors. Cancer Genet. 2014;207(9):358–64. Le Loarer F, Zhang L, Fletcher CD, Ribeiro A, Singer S, Italiano A, et al. Consistent SMARCB1 homozygous deletions in epithelioid sarcoma and in a subset of myoepithelial carcinomas can be reliably detected by FISH in archival material. Genes Chromosomes Cancer. 2014;53(6):475–86. Guillou L, Wadden C, Coindre JM, Krausz T, Fletcher CD. Proximal-type epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series. Am J Surg Pathol. 1997;21(2):130–46. Pawel BR. SMARCB1-deficient Tumors of Childhood: A Practical Guide. Pediatr Dev Pathol. 2018;21(1):6–28. Kim HJ, Kim MH, Kwon J, Kim JY, Park K, Ro JY. Proximal-type epithelioid sarcoma of the vulva with INI1 diagnostic utility. Ann Diagn Pathol. 2012;16(5):411–5. Wang L, Yee-Chang M, Sun W, Melamed J, Simsir A, Shi Y. Myoepithelial carcinoma of soft tissue is a diagnostic challenge on fine-needle aspiration: Case report and review of literature. Diagn Cytopathol. 2022;50(7):E203–9. Shih AR, Cote GM, Chebib I, Choy E, DeLaney T, Deshpande V, et al. Clinicopathologic characteristics of poorly differentiated chordoma. Mod Pathol. 2018;31(8):1237–45. 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A Single-Institute Experience from 2012 to 2022","fulltext":[{"header":"Background","content":"\u003cp\u003eSWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), also known as integrase interactor 1 (INI1), is a crucial component of a chromatin-remodeling protein complex\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. INI1 acts as a tumor suppressor gene, and loss-of-function alterations due to various genetic and/or epigenetic abnormalities give rise to INI1-deficient tumors\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. In 1998, somatic alterations, mainly deletions, in the INI1 gene accompanying loss of expression were identified as a molecular marker of malignant rhabdoid tumors (MRTs) \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Since then, INI1 gene inactivation or loss of expression has been observed in a group of malignancies collectively defined as INI1-deficient tumors\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. The prototypical INI1-deficient tumor is malignant rhabdoid tumor, but numerous other tumor types with the complete loss of INI1 have been described such as epithelioid sarcoma(ES), malignant peripheral nerve sheath tumor(MPNST), almost all of which have a poor prognosis\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. For further insight into INI1-deficient tumor, we reviewed all patients who had INI1-deficient tumor diagnosed and treated in our institution for the past 10 years. In this report, we describe their clinical characteristics, treatment schedules, clinical outcomes, and prognostic factors.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eThe use of immunohistochemistry (IHC) have identified numerous other cancers with the depletion or loss of SMARCB1\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.A retrospective medical record review was conducted on 40 patients treated for INI1-deficient tumor in Beijing Children\u0026rsquo;s Hospital (BCH) between January 2012 to December 2022. All the patients were pathologically confirmed as INI1-deficient tumor by the institutional pathologist based on morphological and immunohistochemical (IHC) evaluations. The basic information of patients was collected by referring to their medical record: age, sex, clinical symptoms, imaging examination, primary tumor sites and metastatic sites, treatment schedules, IHC staining of INI1, and prognosis characteristics. All methods were carried out in accordance with relevant guidelines and regulations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTreatment\u003c/h2\u003e \u003cp\u003ePatients with INI1-deficient tumor were mainly treated with multimodal therapy based on surgery, chemotherapy, radiotherapy. Surgical procedures included biopsy, total resection, subtotal resection, Because of the lack of standardized treatment protocols forNI1-deficient tumor, there were various combinations of chemotherapeutic drugs in this study. The last follow-up was on Oct 30, 2023.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed by SPSS, version 19.0, for Windows (SPSS, Chicago, IL, USA).\u003c/p\u003e \u003cp\u003eContinuous variables were presented by mean with standard deviation, or median and interquartile range if normality hypothesis test rejected the null hypothesis of normal distribution. Student\u0026rsquo;s t test or the Mann-Whitney U test was used for comparing variables between different subgroups. Univariate and multivariate Cox regression analyses were performed for all prognostic factors to screen out independent risk factors. Categorical variables were reported as counts and percentages and were studied using a chi-square test. For the time-to-event analysis, we estimated event-free survival (EFS) and OS with Kaplan-Meier curves. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered as statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePatients and Clinical Characteristics\u003c/h2\u003e \u003cp\u003eA total of 40 patients with INI1-deficient tumors were studied, including 31 with MRT (77.5%), 4 with ES (10.0%, two of them were proximal type), 3 with MPNST (7.5%), 1 with soft tissue myoepithelial carcinoma (2.5%) and 1 with small cell carcinoma of the ovary with hypercalcemia (2.5%). Twenty-one patients were male, and 19 were female, giving a male-to-female ratio of 1.26:1.The median age at presentation was 32.5 months (range, from 11 to 148 months). The median maximum diameters of primary tumors was 5.9cm (range, from 2.5to 21.1cm).Thirteen patients (13/40, 32.5%) had distant stage, including 12 patients had metastasis at the time of diagnosis and 1 patients had metastasis during treatment. The most common site of metastasis was the lung (7/40, 17.5%), other common sites included lymph nodes, liver, bones, and skin.The clinical characteristics are shown in Table\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\u003eThe clinical characteristics of patients with INI1-deficient tumor\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eN\u003c/em\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor Type\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMRTK\u003c/p\u003e \u003cp\u003eEERT\u003c/p\u003e \u003cp\u003eAT/RT\u003c/p\u003e \u003cp\u003eES\u003c/p\u003e \u003cp\u003eMPNST\u003c/p\u003e \u003cp\u003eMEC\u003c/p\u003e \u003cp\u003eSCCOHT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(22.5%)\u003c/p\u003e \u003cp\u003e17(42.5%)\u003c/p\u003e \u003cp\u003e5(12.5%)\u003c/p\u003e \u003cp\u003e4(10%)\u003c/p\u003e \u003cp\u003e3(7.5%)\u003c/p\u003e \u003cp\u003e1(2.5%)\u003c/p\u003e \u003cp\u003e1(2.5%)\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 \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(52.5%)\u003c/p\u003e \u003cp\u003e19(47.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u0026ge;24 months\u003c/p\u003e \u003cp\u003e\u0026lt;24 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24(60.0%)\u003c/p\u003e \u003cp\u003e16(40.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDistant metastasis\u003c/b\u003e\u003c/p\u003e \u003cp\u003eLung\u003c/p\u003e \u003cp\u003eBone\u003c/p\u003e \u003cp\u003eLiver\u003c/p\u003e \u003cp\u003eLymph nodes\u003c/p\u003e \u003cp\u003eSkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(17.5%)\u003c/p\u003e \u003cp\u003e5(12.5%)\u003c/p\u003e \u003cp\u003e2(5.0%)\u003c/p\u003e \u003cp\u003e7(17.5%)\u003c/p\u003e \u003cp\u003e1(2.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eTreatment Schedules\u003c/h2\u003e \u003cp\u003eThere was no standardized treatment option for INI1-deficient tumors, but multimodal therapy was recommended. Treatment schedules are listed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Thirty-six patients received chemotherapy with a median cycle of 5 (1\u0026ndash;14) cycles. Of the 17 cases of EERT,12 patients received tumor resection, including 7 cases of upfront resection and 5 cases of delayed surgery after chemotherapy. Four patient declined therapy after the biopsy or chemotherapy because of tumor rupture and tumor progression and one primary tumors were unresectable even after 6 cycles of induction chemotherapy. For the 9 cases of MRTK, all patients received resection, which included 8 cases of nephrectomy and 1 cases of nephron-sparing surgery. For the 5 cases of AT/RT, 4 patients received upfront resection. For the 3 cases of MPNST, 2patients received upfront resection and 1patient received delayed surgery. For the 4 cases of ES, all patients received upfront resection. Six of the 42 patients received radiation (two patients with MRTK, two with EERT, one with ES and one with AT/RT), and dose and extent of radiation varied upon the primary site and patients\u0026rsquo; age.\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\u003eTreatment schedules of patients with INI1-deficient tumor\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\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEERT\u003c/p\u003e \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMRTK\u003c/p\u003e \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eATRT\u003c/p\u003e \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMPNST\u003c/p\u003e \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eES\u003c/p\u003e \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMEC\u003c/p\u003e \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSCCOHT\u003c/p\u003e \u003cp\u003e\u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003cp\u003eBiospy\u003c/p\u003e \u003cp\u003eTotal resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e9\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eOutcome\u003c/h2\u003e \u003cp\u003eThe EFS rates of 1 year and 3 years for the entire cohort were 51.3%\u0026plusmn;8.0% and 38.9%\u0026plusmn;8.3% respectively.\u003c/p\u003e \u003cp\u003eThe overall survival rates of 1 years and 3 years for the entire cohort were 53.8%\u0026plusmn;8.0% and 43.6%\u0026plusmn;8.6% respectively, and the median OS was 16 months.Tumor progression or recurrence occurred in 25 patients of the entire cohort. Most events (17/25 68%) occurred within 6 months (including 6 months), with a median time of 4 (0.5\u0026ndash;39) months after diagnosis of INI1-deficient tumors. After a median follow up of 14 months (range 0.3\u0026ndash;132.0), 21 patients died, including 6 patients with MRTK, 9 patients with EERT, 5 patients with AT/RT and 1 patients with SCCOHT. Among the 21 dead patients, 20 died from rapid disease progression or recurrence and 1 died from tumor rupture.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eImmunohistochemical characteristics\u003c/h2\u003e \u003cp\u003eAll the children underwent postoperative histopathological immunohistochemical tests. Due to the large number of immunohistochemical items and the large differences between individuals, we listed the test items covering more than 60% of the children \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e(\u003c/span\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e)\u003c/span\u003e. Univariate prognostic correlation analysis was performed on the above collected immunohistochemical data, and it was found that\u0026gt;60% of ki-67 positive areas were associated with poor prognosis (HR 2.75, 95%CI: 1.11\u0026ndash;6.83; P\u0026thinsp;=\u0026thinsp;0.03) \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e(\u003c/span\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003e)\u003c/span\u003e\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\u003eImmunohistochemistry of patients with INI1-deficient tumor\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDead\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\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\u003eN\u0026thinsp;=\u0026thinsp;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINI_1 (%)\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEMA (%)\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (84.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(43.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (40.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDesmin (%)\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23(69.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (39.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(30.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (30.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKi_67\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(47.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14(36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (52.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (34.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (18.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD34(%)\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(22.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(22.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (55.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (29.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(25.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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 \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate analysis of immunohistochemistry of patients with INI1-deficient tumor\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\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINI_1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA-NA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.343\u0026ndash;3.055\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.966\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEMA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.782\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.223\u0026ndash;2.748\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.702\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDesmin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.672\u0026ndash;4.650\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.248\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKi_67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.747\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.105\u0026ndash;6.829\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.03\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 \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePrognostic factors\u003c/h2\u003e \u003cp\u003eAfter survival analysis, we found that survival was not impacted by the age, sex. and tumor diameter. Patients with INI1-deficient non-MRT tumors had a more favorable 3-year OS of 88.9%\u0026plusmn;10.5% vs. 30.3%\u0026plusmn;9.2% for those with INI1-deficient MRT(\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Patients with lung metastasis had a worse prognosis than those without(3-year OS:0% vs. 50.4%\u0026plusmn;9.6%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Patients with\u0026gt;60% of ki-67 positive areas had a worse prognosis than those without(3-year OS:20.8%\u0026plusmn;9.9% vs.63.2%\u0026plusmn;11.1%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). The children with with lung metastasis (HR 8.828, 95%CI: 2.245\u0026ndash;34.711; P\u0026thinsp;=\u0026thinsp;0.002) was an independent risk factor for the prognosis of INI1-deficient tumor.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eHere, we have presented the systematic review of patient characteristics, treatment details, and survival outcomes of patients with INI1-deficient tumor.\u003c/p\u003e \u003cp\u003eINI1is a member of a large protein complex involved in chromatin remodeling and thus regulation of gene expression\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. INI1-deficient cancers are characterized by the biallelic loss of function in both INI1 alleles\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. INI1 immunohistochemistry has emerged as a powerful diagnostic tool to identify INI1-altered neoplasms in routine surgical pathology practice\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. INI1 deficiency is observed as the genetic hallmark in virtually all MRT and in most cases of ES and PDC. In addition, subsets of myoepithelial carcinoma, extraskeletal myxoid chondrosarcoma, and epithelioid peripheral nerve sheath tumors are INI1-deficient\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMRT, a rare tumor occurring almost exclusively in infants and young children, is caused by INI1 biallelic inactivation in virtually all cases\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. MRT can occur in the kidney, central nervous system, or extracranial/extrarenal locations \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. The tumors occur in infants and young children and confer a poor prognosis requiring aggressive therapeutic interventions to improve the chances for survival. In our study, patients with INI1-deficient non-MRT tumors had a more favorable 3-year OS of 88.9%\u0026plusmn;10.5% vs. 30.3%\u0026plusmn;9.2% for those with INI1-deficient MRT(\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). MRTs pose a diagnostic challenge, as they display heterogeneous histopathologic features and differentiate along multiple lineages. The identification of alterations in the INI1 gene in MRT using immunohistochemical staining has lead to improved diagnosis of MRT as well as the discovery of the loss of INI1 expression in some non-MRTs\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eES is a rare and aggressive soft-tissue sarcoma subtype, FISH analysis demonstrates \u003cem\u003eINI1\u003c/em\u003e genomic inactivation through homozygous deletion in 90% of epithelioid sarcomas\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e, along with INI1 loss in 90% of cases, irrespective of histologic subtype. This tumor is cytokeratin and EMA positive, which can be mistaken for myoepithelial carcinoma (MEC) of soft tissue, ES expresses positivity for CD34 but negativity for myoepithelial markers and S100\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. CD34 expression in \u0026gt;\u0026thinsp;50% of ES is helpful to rule out metastatic carcinoma and CD34 immunostaining can be helpful, as this marker is positive in about half of ES and is typically negative in MRTK in Proximal ES\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Some authors realized that diagnostic utility of INI1 in cases with the exclusive composition of epithelioid tumor cells with CD34 negativity\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. (MEC) of soft tissue, also known as malignant myoepithelial tumor, is an uncommon malignancy. Cytologic diagnosis of this entity is challenging due to its rarity and heterogeneous morphology. Wang L et al reported a case with MEC of soft tissue showed loss of INI-1 expression\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePDC, a rare, aggressive tumor originating from notochordal tissue, shows loss of INI1 expression, which occurs in children and young adults, with a peak incidence at 1\u0026ndash;29 years of age (median, 11 years)\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e, An overview of the gene expression profiles from a spectrum of connective tissue tumors suggested that brachyury was uniquely expressed in chordomas, and almost all cases of chordoma including conventional and PDC showed brachyury immunoexpression.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eINI1-deficient tumor is a highly aggressive tumor in children. Lung metastasis was an independent risk factor. Future concerted efforts on more accurate and earlier diagnosis distinguishing from other entities of malignancies, multimodality management, and evaluation of novel therapies are compellingly needed to improve its treatment outcomes and survival.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"478\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.029227557411275%\" valign=\"top\"\u003e\n \u003cp\u003eAbbreviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"65.97077244258872%\" valign=\"top\"\u003e\n \u003cp\u003eEnglish name\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.029227557411275%\" valign=\"top\"\u003e\n \u003cp\u003eATRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"65.97077244258872%\" valign=\"top\"\u003e\n \u003cp\u003eSellar Atypical Teratoid/Rhabdoid Tumors\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.029227557411275%\" valign=\"top\"\u003e\n \u003cp\u003eEERT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"65.97077244258872%\" valign=\"top\"\u003e\n \u003cp\u003eextrarenal extracranial rhabdoid tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.029227557411275%\" valign=\"top\"\u003e\n \u003cp\u003eMRTK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"65.97077244258872%\" valign=\"top\"\u003e\n \u003cp\u003emalignant rhabdoid tumor of the kidney\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.029227557411275%\" valign=\"top\"\u003e\n \u003cp\u003eMPNST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"65.97077244258872%\" valign=\"top\"\u003e\n \u003cp\u003eMalignant Peripheral Nerve Sheath Tumors\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.029227557411275%\" valign=\"top\"\u003e\n \u003cp\u003eMEC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"65.97077244258872%\" valign=\"top\"\u003e\n \u003cp\u003eMyoepithelial carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.029227557411275%\" valign=\"top\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"65.97077244258872%\" valign=\"top\"\u003e\n \u003cp\u003eNumber\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.029227557411275%\" valign=\"top\"\u003e\n \u003cp\u003eSCCOHT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"65.97077244258872%\" valign=\"top\"\u003e\n \u003cp\u003eSmall-cell carcinoma of the ovary, hypercalcemic type.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate Patients and their parents provided written informed consent for the study. This study was performed in line with the principles of the Declaration of Helsinki. Approved by the Ethics Committee of Beijing Children\u0026rsquo;s Hospital, Capital Medical University (number：2018-k-106)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003eThe consent of the child and their parents or legal guardians has been obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The data that support the findings of this study are available from Beijing Children\u0026rsquo;s Hospital but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Beijing Children\u0026rsquo;s Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eThe article was supported by Beijing Natural Science Foundation (No.7222054) and Beijing Research Ward Project (BCRW202101).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYS and XLM designed the study, SHZ, XSW, DWZ, collected the data, HMW, MG were involved in data cleaning, mortality follow-up, LBF, TY analyzed the data. SHZ drafted the manuscript, YS contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003eAll authors would like to thank the participating patients and their families.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKohashi K, Oda Y. Oncogenic roles of SMARCB1/INI1 and its deficient tumors. Cancer Sci. 2017;108(4):547\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgaimy A. SWI/SNF Complex-Deficient Soft Tissue Neoplasms: A Pattern-Based Approach to Diagnosis and Differential Diagnosis. Surg Pathol Clin. 2019;12(1):149\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVersteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;394(6689):203\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuan Z, Yao K, Yang S, Qu Y, Ren M, Zhang Y, et al. Primary adult sellar SMARCB1/INI1-deficient tumor represents a subtype of atypical teratoid/rhabdoid tumor. Mod Pathol. 2022;35(12):1910\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCooper GW, Hong AL. SMARCB1-Deficient Cancers: Novel Molecular Insights and Therapeutic Vulnerabilities. Cancers (Basel). 2022;14(15).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheng JX, Tretiakova M, Gong C, Mandal S, Krausz T, Taxy JB. Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior. Mod Pathol. 2008;21(6):647\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSullivan LM, Folpe AL, Pawel BR, Judkins AR, Biegel JA. Epithelioid sarcoma is associated with a high percentage of SMARCB1 deletions. Mod Pathol. 2013;26(3):385\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeterson CL, Dingwall A, Scott MP. Five SWI/SNF gene products are components of a large multisubunit complex required for transcriptional enhancement. Proc Natl Acad Sci U S A. 1994;91(8):2905\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJudkins AR. Immunohistochemistry of INI1 expression: a new tool for old challenges in CNS and soft tissue pathology. Adv Anat Pathol. 2007;14(5):335\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHollmann TJ, Hornick JL. INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol. 2011;35(10):e47\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCha YJ, Hong CK, Kim DS, Lee SK, Park HJ, Kim SH. Poorly differentiated chordoma with loss of SMARCB1/INI1 expression in pediatric patients: A report of two cases and review of the literature. Neuropathology. 2018;38(1):47\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEaton KW, Tooke LS, Wainwright LM, Judkins AR, Biegel JA. Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. Pediatr Blood Cancer. 2011;56(1):7\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMargol AS, Judkins AR. Pathology and diagnosis of SMARCB1-deficient tumors. Cancer Genet. 2014;207(9):358\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLe Loarer F, Zhang L, Fletcher CD, Ribeiro A, Singer S, Italiano A, et al. Consistent SMARCB1 homozygous deletions in epithelioid sarcoma and in a subset of myoepithelial carcinomas can be reliably detected by FISH in archival material. Genes Chromosomes Cancer. 2014;53(6):475\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuillou L, Wadden C, Coindre JM, Krausz T, Fletcher CD. Proximal-type epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series. Am J Surg Pathol. 1997;21(2):130\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePawel BR. SMARCB1-deficient Tumors of Childhood: A Practical Guide. Pediatr Dev Pathol. 2018;21(1):6\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim HJ, Kim MH, Kwon J, Kim JY, Park K, Ro JY. Proximal-type epithelioid sarcoma of the vulva with INI1 diagnostic utility. Ann Diagn Pathol. 2012;16(5):411\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang L, Yee-Chang M, Sun W, Melamed J, Simsir A, Shi Y. Myoepithelial carcinoma of soft tissue is a diagnostic challenge on fine-needle aspiration: Case report and review of literature. Diagn Cytopathol. 2022;50(7):E203\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShih AR, Cote GM, Chebib I, Choy E, DeLaney T, Deshpande V, et al. Clinicopathologic characteristics of poorly differentiated chordoma. Mod Pathol. 2018;31(8):1237\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"INI1-deficient tumors, Children, Prognostic analysis; Single-Institute","lastPublishedDoi":"10.21203/rs.3.rs-4092439/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4092439/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThis study aims to summarize the clinical features and prognoses of INI1-deficient tumors in children. It further aims to analyze the high-risk factors affecting INI1-deficient tumors prognosis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eClinical data from 40 children with INI1-deficient tumors treated in Beijing Children\u0026rsquo;s Hospital from January 2012 to December 2022, along with the high-risk factors affecting prognosis, were retrospectively analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eForty patients were diagnosed with INI1-deficient tumor at a median age of 32.5 months, including 31cases of malignant rhabdoid tumor, 4 cases of epithelioid sarcoma, 3 cases of malignant peripheral nerve sheath tumor, 1case of soft tissue myoepithelial carcinoma and 1 case of small cell carcinoma of the ovary with hypercalcemia. Thirteen patients(13/40, 32.5%) had metastases at diagnosis. Among the 40 patients, 21 patients died, including 6 patients with MRTK, 9 patients with EERT, 5 patients with AT/RT and 1 patients with SCCOHT. The overall survival rates of 1 years and 3 years for the entire cohort were 53.8%\u0026plusmn;8.0% and 43.6%\u0026plusmn;8.6% respectively. After survival analysis, it was clear that malignant rhabdoid tumor, lung metastasis and ki 67\u0026gt;60% had relatively poor outcomes. Lung metastasis was an independent risk factor for the prognosis of INI1-deficient tumor.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eINI1-deficient tumor is a highly aggressive tumor in children especially with lung metastasis. Much work should do to improve the outcomes and survival for patients with aggressive INI1-deficient tumors.\u003c/p\u003e","manuscriptTitle":"Clinical and Prognostic Characteristics of 40 Cases of INI1-deficient Tumor in Children. A Single-Institute Experience from 2012 to 2022","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-24 16:35:06","doi":"10.21203/rs.3.rs-4092439/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":"4de45d10-9475-4041-9756-326fe98932dc","owner":[],"postedDate":"July 24th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-24T08:50:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-24 16:35:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4092439","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4092439","identity":"rs-4092439","version":["v1"]},"buildId":"cTy_lsJlmDsVRNrSptgXS","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}