دورية أكاديمية
β-Catenin alterations in testicular Leydig cell tumour: a immunohistochemical and molecular analysis.
| العنوان: | β-Catenin alterations in testicular Leydig cell tumour: a immunohistochemical and molecular analysis. |
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| المؤلفون: | Kitagawa Y; Department of Pathology, Indiana University, Indianapolis, IN, USA., De Biase D; Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.; Department of Pharmacy and Biotechnology (FaBit), University of Bologna, Bologna, Italy., Ricci C; DIAP-Dipartimento InterAziendale di Anatomia Patologica di Bologna, Maggiore Hospital, Bologna, Italy.; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy., Cornejo KM; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Fiorentino M; DIAP-Dipartimento InterAziendale di Anatomia Patologica di Bologna, Maggiore Hospital, Bologna, Italy.; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy., Collins K; Department of Pathology, Indiana University, Indianapolis, IN, USA., Idrees MT; Department of Pathology, Indiana University, Indianapolis, IN, USA., Colecchia M; Department of Pathology, San Raffaele Hospital, Universita Vita Salute San Raffaele, Milan, Italy., Ulbright TM; Department of Pathology, Indiana University, Indianapolis, IN, USA., Acosta AM; Department of Pathology, Indiana University, Indianapolis, IN, USA. |
| المصدر: | Histopathology [Histopathology] 2024 Jul; Vol. 85 (1), pp. 75-80. Date of Electronic Publication: 2024 Mar 26. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 7704136 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2559 (Electronic) Linking ISSN: 03090167 NLM ISO Abbreviation: Histopathology Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, Blackwell Scientific Publications. |
| مواضيع طبية MeSH: | beta Catenin*/genetics , beta Catenin*/metabolism , Testicular Neoplasms*/pathology , Testicular Neoplasms*/genetics , Testicular Neoplasms*/metabolism , Leydig Cell Tumor*/pathology , Leydig Cell Tumor*/metabolism , Leydig Cell Tumor*/genetics , Immunohistochemistry*, Humans ; Male ; Adult ; Middle Aged ; Aged ; Young Adult ; Adolescent ; Mutation ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism |
| مستخلص: | Background: Testicular Leydig cell tumours (LCTs) are the most common type of sex cord-stromal tumour in men, representing 1%-3% of all testicular neoplasms. Among testicular sex cord-stromal tumours, CTNNB1 mutations and nuclear expression of β-catenin have been typically associated with Sertoli cell tumour. Recent genomic analyses have shown that CTNNB1 variants are also identified in a subset of LCTs; however, the frequency and clinicopathologic associations of β-catenin alterations remain incompletely understood in this tumour type. Methods: In this study, we evaluated 32 LCTs (five malignant/metastasizing, 27 nonmetastasizing) using β-catenin immunohistochemistry and DNA sequencing. Results: Immunohistochemistry revealed focal or multifocal nuclear β-catenin expression in 47% of the tumours. Diffuse nuclear β-catenin expression (in >50% of the tumour cells) was not detected in any of the cases analysed herein. Comparison of β-catenin-positive and β-catenin-negative cases did not show significant differences in the frequency of adverse histopathologic findings or malignant clinical behaviour. DNA sequencing performed de novo on a subset of seven cases revealed the presence of exon 3 CTNNB1 variants in four of them (4/7, 57%), with variant allele frequencies (VAF) ranging from 7 to 33%. Two additional β-catenin-positive cases that had been sequenced as part of a previous study harboured exon 3 CTNNB1 variants at VAF of 28% and 7%, respectively. Conclusion: These results demonstrate that β-catenin alterations are relatively common in LCT, most likely occurring as subclonal events that are not enriched in cases with aggressive features. Further studies are needed to clarify the oncogenic role of β-catenin in this tumour type. (© 2024 The Authors. Histopathology published by John Wiley & Sons Ltd.) |
| References: | Jou P, Maclennan GT. Leydig cell tumor of the testis. J. Urol. 2009; 181; 2299–2300. Kim I, Young RH, Scully RE. Leydig cell tumors of the testis. A clinicopathological analysis of 40 cases and review of the literature. Am. J. Surg. Pathol. 1985; 9; 177–192. Fankhauser CD, Grogg JB, Hayoz S et al. Risk factors and treatment outcomes of 1,375 patients with testicular Leydig cell tumors: analysis of published case series data. J. Urol. 2020; 203; 949–956. Colecchia M, Bertolotti A, Paolini B et al. The Leydig cell tumour Scaled Score (LeSS): a method to distinguish benign from malignant cases, with additional correlation with MDM2 and CDK4 amplification. Histopathology 2021; 78; 290–299. Rizzo NM, Sholl LM, Idrees MT et al. Comparative molecular analysis of testicular Leydig cell tumors demonstrates distinct subsets of neoplasms with aggressive histopathologic features. Mod. Pathol. 2021; 34; 1935–1946. Perrone F, Bertolotti A, Montemurro G, Paolini B, Pierotti MA, Colecchia M. Frequent mutation and nuclear localization of beta‐catenin in sertoli cell tumors of the testis. Am. J. Surg. Pathol. 2014; 38; 66–71. Zhang C, Ulbright TM. Nuclear localization of beta‐catenin in Sertoli cell tumors and other sex cord‐stromal tumors of the testis: an immunohistochemical study of 87 cases. Am. J. Surg. Pathol. 2015; 39; 1390–1394. Rizzo NM, Sholl LM, Kao CS et al. Molecular correlates of aggressive behavior and biological progression in testicular Sertoli cell tumors. Mod. Pathol. 2023; 36; 100152. Kopanos C, Tsiolkas V, Kouris A et al. VarSome: the human genomic variant search engine. Bioinformatics 2019; 35; 1978–1980. de Biase D, Acquaviva G, Visani M et al. Molecular diagnostic of solid tumor using a next generation sequencing custom‐designed multi‐gene panel. Diagnostics (Basel) 2020; 10; 250. Bartsch DK, Hasse C, Schug C, Barth P, Rothmund M, Höppner W. A RET double mutation in the germline of a kindred with FMTC. Exp. Clin. Endocrinol. Diabetes 2000; 108; 128–132. Chamlian A, Benkoel L, Gulian JM. Ultrastructural study of lobular glycogen heterogeneity in human liver. Cell. Mol. Biol. 1987; 33; 547–554. Siegmund S, Ricci C, Kao CS et al. Germline APC alterations may predispose to testicular sex cord‐stromal tumors. Am. J. Surg. Pathol. 2023; 47; 1432–1437. |
| فهرسة مساهمة: | Keywords: CTNNB1; Leydig cell tumour; sex cord‐stromal tumour; testis; β‐catenin |
| المشرفين على المادة: | 0 (beta Catenin) 0 (CTNNB1 protein, human) 0 (Biomarkers, Tumor) |
| تواريخ الأحداث: | Date Created: 20240326 Date Completed: 20240608 Latest Revision: 20240618 |
| رمز التحديث: | 20240618 |
| DOI: | 10.1111/his.15175 |
| PMID: | 38530207 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1365-2559 |
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| DOI: | 10.1111/his.15175 |