Diagnostic importance of hepatocyte nuclear factor 1 beta (HNF1β) in testicular tumors and its sensitivity for the detection of yolk sac tumors: an immunohistochemical analysis

Year 2022, Volume: 8 Issue: 4, 497 - 505, 04.07.2022

Remzi Arslan

https://doi.org/10.18621/eurj.1112501

Abstract

Objectives: Testicular tumors are common solid malignancies in young fertile men, and most are germ cell tumors. In general, they originate from a single germ cell and transform into different tumor types or present with the coexistence of different morphological patterns. Due to the heterogeneity of these tumors, immunohistochemical markers are frequently used in their differential diagnosis. In recent years, some studies have indicated hepatocyte nuclear factor 1 beta (HNF1β) can be used in the differential diagnosis of testicular tumors, especially yolk sac tumors (YSTs). In this study, we aimed to investigate the general expression status of HNF1β in all testicular tumors and determine its importance in YST detection.

Methods: A total of 144 testicular tumors treated with orchiectomy between 2011 and 2020 were included in our study. The pathological diagnosis reports of these cases were retrospectively reviewed and their general prognostic features were determined. HNF1β immunohistochemical staining was applied to the characteristic paraffin blocks representing the lesions. Staining was evaluated in terms of severity and prevalence.

Results: Most cases (38.2%) were seminomas, followed by mixed germ cell tumors (34.0%, 49/144), embryonic carcinomas (7.6%), pure YSTs (4.9%), and others (Leydig cell tumors, mesenchymal tumors, lymphomas, etc.). No HNF1β immunostaining was observed in any of the seminomatous lesions. A high level of staining was present in almost all the pure YSTs and tumor areas with the YST component. HNF1β had a specificity of 95.1% and sensitivity of 87.1% in the detection of YSTs.

Conclusions: HNF1β has high specificity and sensitivity in detecting YSTs among testicular tumors, and therefore we consider that it can be routinely used to detect the presence of YSTs, especially in patients with mixed germ cell tumors.

Keywords

Testicular germ cell tumor, seminoma, yolk sac tumor, hepatocyte nuclear factor 1 beta (HNF1β)

Supporting Institution

This study was financially supported by the Scientific Research Projects Unit of Atatürk University Rectorate.

Project Number

8700

References

• 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7-30.
• 2. Bray F, Richiardi L, Ekbom A, Pukkala E, Cuninkova M, Møller H. Trends in testicular cancer incidence and mortality in 22 European countries: continuing increases in incidence and declines in mortality. Int J Cancer 2006;118:3099-111.
• 3. Trabert B, Chen J, Devesa SS, Bray F, McGlynn KA. International patterns and trends in testicular cancer incidence, overall and by histologic subtype, 1973-2007. Andrology 2015;3:4-12.
• 4. Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol 2016;70:93-105.
• 5. Cheng L, Albers P, Berney DM, Feldman DR, Daugaard G, Gilligan T, et al. Testicular cancer. Nat Rev Dis Primers 2018;4:29.
• 6. Bingham C, Hattersley AT. Renal cysts and diabetes syndrome resulting from mutations in hepatocyte nuclear factor-1beta. Nephrol Dial Transplant 2004;19:2703-8.
• 7. Gudmundsson J, Sulem P, Steinthorsdottir V, Bergthorsson JT, Thorleifsson G, Manolescu A, et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet 2007;39:977-83.
• 8. Mendel DB, Hansen LP, Graves MK, Conley PB, Crabtree GR. HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. Genes Dev 1991;5:1042-56.
• 9. Horikawa Y, Iwasaki N, Hara M, Furuta H, Hinokio Y, Cockburn BN, et al. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet 1997;17:384-5.
• 10. Terasawa K, Toyota M, Sagae S, Ogi K, Suzuki H, Sonoda T, et al. Epigenetic inactivation of TCF2 in ovarian cancer and various cancer cell lines. Br J Cancer 2006;94:914-21.
• 11. Rougemont AL, Tille JC. Role of HNF1β in the differential diagnosis of yolk sac tumor from other germ cell tumors. Hum Pathol 2018;81:26-36.
• 12. Gallo A, Fankhauser C, Hermanns T, Beyer J, Christiansen A, Moch H, et al. HNF1β is a sensitive and specific novel marker for yolk sac tumor: a tissue microarray analysis of 601 testicular germ cell tumors. Mod Pathol 2020;33:2354-60.
• 13. Park CK, Shin SJ, Cho YA, Joo JW, Cho NH. HoxB13 expression in ductal type adenocarcinoma of prostate: clinicopathologic characteristics and its utility as potential diagnostic marker. Sci Rep 2019;9:20205.
• 14. Honecker F, Aparicio J, Berney D, Beyer J, Bokemeyer C, Cathomas R, et al. ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up. Ann Oncol 2018;29:1658-86.
• 15. Coffinier C, Gresh L, Fiette L, Tronche F, Schütz G, Babinet C, et al. Bile system morphogenesis defects and liver dysfunction upon targeted deletion of HNF1beta. Development 2002;129:1829-38.
• 16. Edghill EL, Bingham C, Ellard S, Hattersley AT. Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet 2006;43:84-90.
• 17. Kato N, Tamura G, Motoyama T. Hypomethylation of hepatocyte nuclear factor-1beta (HNF-1beta) CpG island in clear cell carcinoma of the ovary. Virchows Arch 2008;452:175-80.
• 18. Azmi AS, Bao GW, Gao J, Mohammad RM, Sarkar FH. Network insights into the genes regulated by hepatocyte nuclear factor 4 in response to drug induced perturbations: a review. Curr Drug Discov Technol 2013;10:147-54.
• 19. Yu DD, Guo SW, Jing YY, Dong YL, Wei LX. A review on hepatocyte nuclear factor-1beta and tumor. Cell Biosci 2015;5:58.
• 20. Shim JH, Lee HC, Han S, Kang HJ, Yu E, Lee SG. Hepatocyte nuclear factor 1β is a novel prognostic marker independent of the Milan criteria in transplantable hepatocellular carcinoma: a retrospective analysis based on tissue microarrays. Liver Transpl 2013;19:336-45.
• 21. Tsuchiya A, Sakamoto M, Yasuda J, Chuma M, Ohta T, Ohki M, et al. Expression profiling in ovarian clear cell carcinoma: identification of hepatocyte nuclear factor-1 beta as a molecular marker and a possible molecular target for therapy of ovarian clear cell carcinoma. Am J Pathol 2003;163:2503-12.
• 22. Yamamoto S, Tsuda H, Aida S, Shimazaki H, Tamai S, Matsubara O. Immunohistochemical detection of hepatocyte nuclear factor 1beta in ovarian and endometrial clear-cell adenocarcinomas and nonneoplastic endometrium. Hum Pathol 2007;38:1074-1080.
• 23. Kao YC, Lin MC, Lin WC, Jeng YM, Mao TL. Utility of hepatocyte nuclear factor-1β as a diagnostic marker in ovarian carcinomas with clear cells. Histopathology 2012;61:760-8.
• 24. Kim L, Liao J, Zhang M, Talamonti M, Bentrem D, Rao S, et al. Clear cell carcinoma of the pancreas: histopathologic features and a unique biomarker: hepatocyte nuclear factor-1beta. Mod Pathol 2008;21:1075-83.
• 25. Silva TD, Vidigal VM, Felipe AV, DE Lima JM, Neto RA, Saad SS, et al. DNA methylation as an epigenetic biomarker in colorectal cancer. Oncol Lett 2013;6:1687-92.
• 26. Buchner A, Castro M, Hennig A, Popp T, Assmann G, Stief CG, et al. Downregulation of HNF-1B in renal cell carcinoma is associated with tumor progression and poor prognosis. Urology 2010;76:507.e6-11.
• 27. Nogales FF, Prat J, Schuldt M, Cruz-Viruel N, Kaur B, D'Angelo E, et al. Germ cell tumour growth patterns originating from clear cell carcinomas of the ovary and endometrium: a comparative immunohistochemical study favouring their origin from somatic stem cells. Histopathology 2018;72:634-47.
• 28. Fadare O, Zhao C, Khabele D, Parkash V, Quick CM, Gwin K, et al. Comparative analysis of Napsin A, alpha-methylacyl-coenzyme A racemase (AMACR, P504S), and hepatocyte nuclear factor 1 beta as diagnostic markers of ovarian clear cell carcinoma: an immunohistochemical study of 279 ovarian tumours. Pathology 2015;47:105-11.