RSS-Feed abonnieren

DOI: 10.1055/s-0045-1804500
Study of Immunohistochemical Expression Patterns of Mismatch Repair Proteins in Endometrial Carcinoma and Endometrial Hyperplasia: An Institutional Study
Authors
Funding The study was partly funded by the “Institutional Post Graduate Research Grant” provided by the university.

Abstract
Introduction Endometrial carcinoma (EC) is the most common cancer in women (7% of all malignancies) standing fourth in prevalence. Its molecular categorization has lately gained substantial importance, because of its prognostic implications and association of mismatch repair (MMR) proteins with Lynch syndrome.
Objectives Our aim of the study was to analyze the expression of MMR proteins (MLH1, PMS2, MSH6, MSH2) in EC and Endometrial hyperplasia (EH).
Materials and Methods This study was performed on 52 EC and 65 EH cases (7 cases - disordered proliferative endometrium, 12 cases - EH with atypia, 46 cases - EH without atypia). Immunohistochemical staining with MLH1, PMS2, MSH6, and MSH2 were performed. SSPS software version 25 with chi-square test was used in statistical analysis.
Results Out of 52 cases of EC, 42 (80.76%) cases were identified as MMRd.MLH1 negative expression, which was significant (p: 0.005) compared with other markers. Also, there was significant statistical correlation (p: 0.004) between lower International Federation of Gynecology and Obstetrics grade and MLH1/PMS2 loss. Only six cases of EC had notable family history. Of 12 cases of EH with atypia, 91.66% (11/12) were MMR deficient (MMRd), whereas in EH without atypia 69.23% (32/46) were of MMRd. Paired expression of MLH1/PMS2 and MSH2/MSH6 was observed in EC whereas it was not seen in EH. MLH1 loss was the most common protein loss both in EC and EH with atypia.
Conclusion MLH1/PMS2 combination was the most common protein deficiency seen in EC. We found considerable proportion of EC cases with MMRd. This implies the need of incorporating routine MMR protein assessment by immunohistochemistry in all the patients diagnosed as EC as it will affect the further treatment and management.
Publikationsverlauf
Artikel online veröffentlicht:
20. Februar 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
-
References
- 1 Mathur P, Sathishkumar K, Chaturvedi M. et al; ICMR-NCDIR-NCRP Investigator Group. Cancer Statistics, 2020: report from National Cancer Registry Programme, India. JCO Glob Oncol 2020; 6: 1063-1075
- 2 Yang G, Zheng RY, Jin ZS. Correlations between microsatellite instability and the biological behaviour of tumours. J Cancer Res Clin Oncol 2019; 145 (12) 2891-2899
- 3 Bianco B, Barbosa CP, Trevisan CM, Laganà AS, Montagna E. Endometrial cancer: a genetic point of view. Transl Cancer Res 2020; 9 (12) 7706-7715
- 4 Zhao S, Chen L, Zang Y. et al. Endometrial cancer in Lynch syndrome. Int J Cancer 2022; 150 (01) 7-17
- 5 Sharma A, Kamboj M, Panaych A. et al. Assessment of mismatch repair protein expression by immunohistochemistry in endometrial carcinomas with clinicopathological correlation: a study from Indian tertiary cancer care centre. Int J Mol Immuno Oncol. 2020; 5 (03) 101-107
- 6 Lucas E, Chen H, Molberg K. et al. Mismatch repair protein expression in endometrioid intraepithelial neoplasia/atypical hyperplasia: should we screen for Lynch syndrome in precancerous lesions?. Int J Gynecol Pathol 2019; 38 (06) 533-542
- 7 Sanderson PA, Esnal-Zufiaurre A, Arends MJ. et al. Improving the diagnosis of endometrial hyperplasia using computerized analysis and immunohistochemical biomarkers. Front Reprod Health 2022; 4: 896170
- 8 Hardisson D, Moreno-Bueno G, Sánchez L. et al. Tissue microarray immunohistochemical expression analysis of mismatch repair (hMLH1 and hMSH2 genes) in endometrial carcinoma and atypical endometrial hyperplasia: relationship with microsatellite instability. Mod Pathol 2003; 16 (11) 1148-1158
- 9 Mutter GL, Lax SF. Endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia. In: WHO Classification of Tumours Editorial Board, ed. Female Genital Tumours, WHO Classification of Tumours Series. 5th ed.. Vol. 4. Lyon, France: International Agency for Research on Cancer; 2020: 250-251
- 10 Jovanovic AS, Boynton KA, Mutter GL. Uteri of women with endometrial carcinoma contain a histopathological spectrum of monoclonal putative precancers, some with microsatellite instability. Cancer Res 1996; 56 (08) 1917-1921
- 11 Orbo A, Nilsen MN, Arnes MS, Pettersen I, Larsen K. Loss of expression of MLH1, MSH2, MSH6, and PTEN related to endometrial cancer in 68 patients with endometrial hyperplasia. Int J Gynecol Pathol 2003; 22 (02) 141-148
- 12 Esteller M, Catasus L, Matias-Guiu X. et al. hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis. Am J Pathol 1999; 155 (05) 1767-1772
- 13 Pai RK, Dudley B, Karloski E. et al. DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome. Mod Pathol 2018; 31 (10) 1608-1618
- 14 Wang S, Guan G, Zou C. et al. Genome profiling of mismatch repair genes in eight types of tumors. Cell Cycle 2021; 20 (11) 1091-1106
- 15 McMeekin DS, Tritchler DL, Cohn DE. et al. Clinicopathologic significance of mismatch repair defects in endometrial cancer: an NRG oncology/gynecologic oncology group study. J Clin Oncol 2016; 34 (25) 3062-3068
- 16 Talhouk A, McConechy MK, Leung S. et al. A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer 2015; 113 (02) 299-310
- 17 Puangsricharoen P, Manchana T, Ariyasriwatana C, Triratanachat S. Immunohistochemistry staining for the mismatch repair proteins in endometrial cancer patients. Thai J Obstet Gynaecol. 2020; 28: 79-85
- 18 Hashmi AA, Mudassir G, Hashmi RN. et al. Microsatellite instability in endometrial carcinoma by immunohistochemistry, association with clinical and histopathologic parameters. Asian Pac J Cancer Prev 2019; 20 (09) 2601-2606
- 19 Doghri R, Houcine Y, Boujelbène N. et al. Mismatch repair deficiency in endometrial cancer: immunohistochemistry staining and clinical implications. Appl Immunohistochem Mol Morphol 2019; 27 (09) 678-682
- 20 Jain E, Prasad S, Dhar A, Kini L, Sharma S, Dewan A. The utility of evaluating mismatch repair proteins in endometrial carcinoma: an experience from a tertiary referral centre in North India. Pathologica 2021; 113 (02) 115-120
- 21 Tangjitgamol S, Kittisiam T, Tanvanich S. Prevalence and prognostic role of mismatch repair gene defect in endometrial cancer patients. Tumour Biol 2017; 39 (09) 1010428317725834
- 22 Kato M, Takano M, Miyamoto M. et al. DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers. J Gynecol Oncol 2015; 26 (01) 40-45
- 23 Ramchander NC, Ryan NAJ, Walker TDJ. et al. Distinct immunological landscapes characterize inherited and sporadic mismatch repair deficient endometrial cancer. Front Immunol 2020; 10: 3023
- 24 Lacin S, Tasar GE, Usubutun A. et al. The prognostic significance of microsatellite status and its relationship with tumor-infiltrating lymphocyte in endometrial cancer. Eur J Gynaecol Oncol 2021; 42 (03) 541-547
- 25 Bounous VE, Ferrero A, Campisi P. et al. Immunohistochemical markers and TILs evaluation for endometrial carcinoma. J Clin Med 2022; 11 (19) 1-13
- 26 Chavez JA, Wei L, Suarez AA, Parwani AV, Li Z. Clinicopathologic characteristics, tumor infiltrating lymphocytes and programed cell death ligand-1 expression in 162 endometrial carcinomas with deficient mismatch repair function. Int J Gynecol Cancer 2019; 29 (01) 113-118
- 27 Ismael NEHS, Naguib HM, Talaat SM, Bakry RF. Mismatch repair proteins (Mlh1, msh2, msh6, and pms2) immunohistochemical expression and microsatellite instability in endometrial carcinoma. Open Access Maced J Med Sci 2020; 8: 306-310
- 28 Fountzilas E, Kotoula V, Pentheroudakis G. et al. Prognostic implications of mismatch repair deficiency in patients with nonmetastatic colorectal and endometrial cancer. ESMO Open 2019; 4 (02) e000474
- 29 Mwafy S, El-Anwar N, Eid AM. Mismatch repair status in endometrioid type of endometrial carcinoma: association with clinicopathological parameters. Int J Cancer Biomed Res. 2020; 4: 209-215
- 30 Antill Y, Buchanan DD, Scott CL. Mismatch repair and clinical response to immune checkpoint inhibitors in endometrial cancer. Cancer 2022; 128 (06) 1157-1161
- 31 Nieminen TT, Gylling A, Abdel-Rahman WM. et al. Molecular analysis of endometrial tumorigenesis: importance of complex hyperplasia regardless of atypia. Clin Cancer Res 2009; 15 (18) 5772-5783
- 32 Han SJ, Kim MK. Clinical significance of mismatch repair genes immunohistochemical expression of complex endometrial hyperplasia. Obstet Gynecol Sci 2015; 58 (02) 106-111
- 33 Catena U, Della Corte L, Raffone A. et al. Fertility-sparing treatment for endometrial cancer and atypical endometrial hyperplasia in patients with Lynch syndrome: molecular diagnosis after immunohistochemistry of MMR proteins. Front Med (Lausanne) 2022; 9: 948509
- 34 Raffone A, Catena U, Travaglino A. et al. Mismatch repair-deficiency specifically predicts recurrence of atypical endometrial hyperplasia and early endometrial carcinoma after conservative treatment: a multi-center study. Gynecol Oncol 2021; 161 (03) 795-801