Molecular markers of endometrial carcinoma and associated clinicopathological features

Ekaterina Igorevna Koroleva; Королёва Екатерина Игоревна; Aram Ashotovich Musaelyan; Мусаелян Арам Ашотович; Vladimir Dmitrievich Nazarov; Назаров Владимир Дмитриевич; Sergej Vladimirovich Lapin; Лапин Сергей Владимирович; Sergey Leonidovich Vorobev; Воробьев Сергей Леонидович; Olga Lvovna Sharova; Шарова Ольга Львовна; Evgeniya Sergeevna Kozorezova; Козорезова Евгения Сергеевна; Inna Mihaylovna Korablina; Кораблина Инна Михайловна; Vladimir Leonidovich Emanuel; Эмануэль Владимир Леонидович; Sergey Vladimirovich Orlov; Орлов Сергей Владимирович

doi:10.29296/24999490-2022-03-06

Molecular markers of endometrial carcinoma and associated clinicopathological features

Authors: Koroleva E.I.¹, Musaelyan A.A.¹^,2, Nazarov V.D.¹, Lapin S.V.¹, Vorobev S.L.³, Sharova O.L.³, Kozorezova E.S.³, Korablina I.M.³, Emanuel V.L.¹, Orlov S.V.¹^,2
Affiliations:
1. P. Pavlov First Saint-Petersburg State Medical University
2. Federal State Budget Research Institution "Research Institute of Medical Primatology"
3. National Center for Clinical Morphological Diagnostics
Issue: Vol 20, No 3 (2022)
Pages: 34-40
Section: Articles
URL: https://journal-vniispk.ru/1728-2918/article/view/143941
DOI: https://doi.org/10.29296/24999490-2022-03-06
ID: 143941

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Abstract

Introduction. In 2013 The Cancer Genome Atlas research group divided the molecular aberrations in endometrial cancer into four subtypes: POLE mutations, microsatellite instability, copy-number low and copy-number high. These subtypes have different prognosis and could probably mean different therapeutical options. The aim of the study. To estimate the prevalence of different molecular aberrations and to find out associated clinicopathological features. Methods. The study included 45 samples of endometrial carcinoma. Pathological structure and molecular features of each sample were evaluated. Immunohistochemical testing was used to find out the level of p53 expression. Genetic testing was carried out by PCR for MSI testing and by sequencing POLE exon 9 and exon 13 for point mitations. Results. Nor POLE mutations, nor abnormal p53 expression level were found in studied samples. The prevalence was 22% for MSI tumors. No significant difference in clinicopathological features was found between MSI and MSS tumors except for mitotic index that was higher in MSI tumors. Similarly, MSI tumors were less differentiated but the difference was not statistically significant. Conclusion. POLE mutations and abnormal p53 level are rare in low-grade endometrial carcinomas. Nevertheless, MSI tumors are common in this group and further research of their prognostic significance is important.

Keywords

POLE, MSI, p53, endometrial cancer, molecular classification, POLE, MSI, p53

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References

McAlpine J., Leon-Castillo A., Bosse T The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses. J. Pathol. 2018; 244 (5): 538-49. https://doi.org/10.1002/path.5034
Levine D., The Cancer Genome Atlas Research Network.Integrated genomic characterization of endometrial carcinoma. Nature. 2013; 497: 67-73. https://doi.org/10.1038/nature12113
Stelloo E., Bosse T., Nout R.A., MacKay H.J., Church D.N., Nijman H.W., Leary A., Edmondson R.J., Powell M.E., Crosbie E.J., Kitchener H.C., Mileshkin L., Pollock P.M., Smit V.T., Creutzberg C.L. Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a Trans-PORTEC initiative. Mod. Pathol. 2015; 28: 836-44. https://doi.org/10.1038/mod-pathol.2015.43
Talhouk A., McConechy M.K., Leung S., Yang W., Lum A., Senz J., Boyd N., Pike J., Anglesio M., Kwon J.S., Karnezis A.N., Huntsman D.G., Gilks C.B., McAlpine J.N. Confirmation of ProMisE: A simple, genomics-based clinical classifier for endometrial cancer. Cancer. 2017; 123 (5): 802-13. doi: 10.1002/cncr.30496
Imboden S., Nastic D., Ghaderi M., Rydberg F., Rau T.T., Mueller M.D., Epstein E., Carlson J.W. Phenotype of POLE-mutated endometrial cancer. PLoS ONE. 2019; 14 (3): e0214318. https://doi.org/10.1371/journal.pone.0214318
Kanopiene D., Vidugiriene J., Valuckas K. P, Smailyte G., Uleckiene S., Bacher J. Endometrial cancer and microsatellite instability status. Open medicine. 2014; 10 (1): 70-6. https://doi.org/10.1515/med-2015-0005
Hashmi A.A., Mudassir G., Hashmi R.N., Irfan M., Asif H., Khan E.Y, Abu Bakar S.M., Faridi N. Microsatellite Instability in Endometrial Carcinoma by Immunohistochemistry, Association with Clinical and Histopathologic Parameters. Asian Pac. J. Cancer Prev. 2019; 20 (9): 2601-6. https://doi.org/10.31557/APJCP2019.20.9.2601.
National Comprehensive Cancer Network Guidelines 3.2021 Uterine Neoplasms, 2021. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1473.
Maxwell G.L., Risinger J.I., Alvarez A.A., Barrett J.C., Berchuck A. Favorable survival associated with microsatellite instability in endometrioid endometrial cancers. Obstet. Gynecol. 2001; 97 (3): 417-22. https://doi.org/10.1016/s0029-7844(00)01165-0.
Murali R., Davidson B., Fadare O., Carlson J.A., Crum C.P., Gilks C.B., Irving J.A., Malpica A., Matias-Guiu X., McCluggage W.G., Mittal K., Oliva E., Parkash V, Rutgers J.K.L., Staats PN., Stewart C.J.R., Tornos C., Soslow R.A. High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations.Int. J. Gynecol. Pathol. 2019; 38 (Iss 1 Suppl 1): 40-63. https://doi.org/10.1097/PGP0000000000000491
An H.J., Kim K.I., Kim J.Y, Shim J.Y, Kang H., Kim T.H., Kim J.K., Jeong J.K., Lee S.Y, Kim S.J. Microsatellite Instability in Endometrioid Type Endometrial Adenocarcinoma is Associated With Poor Prognostic Indicators. Am. J. Surg. Pathol. 2007; 31 (6): 846-53. https://doi.org/10.1097/01.pas.0000213423.30880.ac
Yano M., Ito K., Yabuno A., Ogane N., Katoh T., Miyazawa M., Miyazawa M., Hasegawa K, Narahara H, Yasuda M. Impact of TP53 immunohistochemistry on the histological grading system for endometrial endometrioid carcinoma. Mod. Pathol. 2019; 32: 1023-31. https://doi.org/10.1038/s41379-019-0220-1
Bell D. W., Ellenson L. H. Molecular Genetics of Endometrial Carcinoma. Annu. Rev Pathol. 2017; 14 (1). https://doi.org/10.1146/annurev-pathol-020117-043609
Schultheis A.M., Martelotto L.G., De Filippo M.R., Piscuglio S., Ng C.K., Hussein Y.R., Reis-Filho J.S., Soslow R.A., Weigelt B. TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers.Int. J. Gynecol. Pathol. 2016; 35 (4): 289-300. https://doi.org/10.1097/pgp.0000000000000243
Luchini C., Bibeau F, Ligtenberg M.J.L., Singh N., Nottegar A., Bosse T., Miller R., Riaz N., Douillard J.Y, Andre F, Scarpa A. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann. Oncol. 2019; 30 (8): 1232-43. https://doi.org/10.1093/annonc/mdz116.
McConechy M.K., Talhouk A., Leung S., Chiu D., Yang W., Senz J., Reha-Krantz L.J., Lee C.H., Huntsman D.G., Gilks C.B., McAlpine J.N. Endometrial Carcinomas with POLE Exonuclease Domain Mutations Have a Favorable Prognosis. Clin. Cancer Res. 2016; 22 (12): 2865-73. https://doi.org/10.1158/1078-0432.CCR-15-2233.
Buttin B.M., Powell M.A., Mutch D.G., Rader J.S., Herzog T.J., Gibb R.K., Huettner P, Edmonston T.B., Goodfellow PJ. Increased risk for hereditary nonpolyposis colorectal cancer-associated synchronous and metachronous malignancies in patients with microsatellite instability-positive endometrial carcinoma lacking MLH1 promoter methylation. Clin. Cancer Res. 2004; 10 (2): 481-90. https://doi.org/10.1158/1078-0432.ccr-1110-03.
Steinbakk A., Malpica A., Slewa A., Gudlaugsson E., Janssen E.A., Arends M., Kruse A.J., Yinhua Y, Feng W., Baak J.P. High frequency microsatellite instability has a prognostic value in endometrial endometrioid adenocarcinoma, but only in FIGO stage 1 cases. Anal. Cell Pathol. (Amst). 2010; 33 (5): 245-55. https://doi.org/10.3233/ACP-CLO-2010-0550
Walsh M.D., Buchanan D.D., Cummings M.C., Pearson S.A., Arnold S.T., Clendenning M., Walters R., McKeone D.M., Spurdle A.B., Hopper J.L., Jenkins M.A., Phillips K.D., Suthers G.K., George J., Goldblatt J., Muir A., Tucker K., Pelzer E., Gattas M.R., Woodall S., Parry S., Macrae FA., Haile R.W., Baron J.A., Potter J.D., Le Marchand L., Bapat B., Thibodeau S.N., Lindor N.M., McGuckin M.A., Young J.P Lynch Syndrome-Associated Breast Cancers: Clinicopathologic Characteristics of a Case Series from the Colon Cancer Family Registry. Clin. Cancer Res. 2010; 16 (7): 2214-24. https://doi.org/10.1158/1078-0432.ccr-09-3058
Al Kushi A., Lim P, Aquino-Parsons C., Gilks C. B. Markers of Proliferative Activity Are Predictors of Patient Outcome for Low-Grade Endometrioid Adenocarcinoma But Not Papillary Serous Carcinoma of Endometrium. Mod. Pathol. 2002; 15 (4): 365-71. https://doi.org/10.1038/mod-pathol.3880531