Mismatch repair defects in endometrial cancer

Abstract

Endometrial cancer is the most commonly diagnosed gynecologic malignancy among women worldwide and may be classified on the basis of different molecular, pathologic and genetic alterations. Identification of mismatch repair-deficient (MMRd), which occur in up to 30% of all endometrial cancers (EC), has become unavoidable for therapeutic management, clinical desicion making, and prognosis. Although microsatellite instability is associated with a more favorable outcome in colorectal cancer, its relationship with prognosis in EC is not yet clear.

Keywords

• Endometrial Cancer
• Mismatch Repair
• Prognosis

Mismatch repair gen defektlerinin endometrium kanserindeki önemi

Abstract

Endometrium kanseri dünya genelinde en yaygın görülen jinekolojik kanserdir ve farklı moleküler, patolojik ve genetik değişikliklere göre sınıflandırılır. Yaklaşık %30 oranında görülen mismatch repair defekti (MMRd)’nin tespiti, tedavi yönetimi, klinik karar verme süreci ve prognoz ile ilişkisinden dolayı vazgeçilmez bir duruma gelmiştir. Kolorektal kanserlerde mikrosatellit instabilite daha iyi prognozla ilişkili olmasına rağmen, bu ilişki endometrium kanserinde henüz netlik kazanmamıştır.

Keywords

• Endometrial Kanser
• Mismatch Repair
• Prognoz

References

1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J. Clin. 2021, 71, 7–33, Erratum in CA Cancer J. Clin. 2021, 71, 359.
2. Garg K, Soslow RA. Endometrial carcinoma in women aged 40 years and younger. Arch Pathol Lab Med, 2014 138(3): p. 335–42.
3. Wise MR, Gill P, Lensen S, Thompson JMD, Farquhar JM. Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women. Am J Obstet Gynecol, 2016 215(5): p. 598 e1–598 e8.
4. American Cancer Society. Endometrial cancer survival rates, by stage, https://www.cancer.org/ cancer/endometrial-cancer/detection-diagnosis-staging/survival-rates.html; https://www.cancer. org/cancer/endometrial-cancer/d (accessed 5 March 2021).
5. Colombo N, Creutzberg C, Amant F, Bosse T, Gonzalez-Martin A, Ledermann J, et al. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: diagnosis, treatment and follow-up. Ann Oncol 2016; 27: 16–41.
6. Mitric C, Bernardini MQ. Endometrial Cancer: Transitioning from Histology to Genomics. Curr Oncol. 2022 Jan 31;29(2):741-757.
7. Jamieson A, Bosse T, McAlpine JN. The emerging role of molecular pathology in directing the systemic treatment of endometrial cancer. Ther Adv Med Oncol. 2021 Aug 14;13:17588359211035959.
8. Favier A, Varinot J, Uzan C, Duval A, Brocheriou I, Canlorbe G. The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systemic Review. Cancers (Basel). 2022 Aug 3;14(15):3783.

9. Walsh MD, Buchanan DD, Cummings MC, Pearson S, Arnold ST, Clendenning M, et al. Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry. Clin Cancer Res 2010; 16:2214.
10. Muto M. Risk-reducing salpingo-oophorectomy in patients at high risk of epithelial ovarian and fallopian tube cancer. Sep 2021.
11. Modesitt SC. Missed opportunities for primary endometrial cancer prevention: How to optimize early identification and treatment of high-risk women. Obstet Gynecol. 2012;120:989–991.
12. Lancester JM, Powell CB, Kauff ND, Cass I, Chen L, Lu KH, et al. Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol 2007;107: 159-162.
13. Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer. Am J Gastroenterol. 2014;109(8):1159–1179.
14. Committee on Practice Bulletins-Gynecology; Society of Gynecologic Oncology. ACOG Practice Bulletin No. 147: Lynch syndrome. Obstet Gynecol. 2014;124(5):1042–1054.
15. Sonoda K. Molecular biology of gynecological cancer. Oncol Lett, 2016 11(1): p. 16–22.
16. Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz J, et al. Confirmation of ProMisE: A simple, genomics-based clinical classifier for endometrial cancer. Cancer 2017, 123, 802–813.
17. Diaz-Padilla I, Romero N, Amir E, Matias-Guiu X, Vilar E, Muggia F, et al. Mismatch repair status and clinical outcome in endometrial cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2013 Oct;88(1):154-67.
18. Kanopiene D, Vidugiriene J, Valuckas P, Smailyte G, Ulckiene S, Bacher J. Endometrial cancer and microsatellite status. Open Med (Wars). 2014 Nov 11;10(1):70-76.
19. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Rüschoff J, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96: 261– 268.
20. Bellone S, Roque DM, Ms ERS, Buza N, Hui P, Ms EB, et al. A phase 2 evaluation of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability. Cancer 2021, 2021, 34025.
21. Stelloo E, Jansen AML, Osse EM, Nout RA, Creutzberg CL, Ruano D, et al. Practical guidance for mismatch repair-deficiency testing in endometrial cancer. Ann Oncol. 2017;28: 96–102.
22. Cho KR, Cooper K, Croce S, Djordevic B, Herrington S, Howitt B, et al. International Society of Gynecological Pathologists (ISGyP) endometrial cancer project: guidelines from the special techniques and ancillary studies group. Int J Gynecol Pathol 2019;38 Suppl 1:S114–22.
23. Kurnit KC, Westin SN, Coleman RL. Microsatellite instability in endometrıal cancer: new purpose for an old test. Cancer. 2019 Jul 1;125(13):2154-2163.
24. Goodfellow PJ, Billingsley CC, Lankes HA, Lankes HA, Ali S, Cohn DE, et al. Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study. J Clin Oncol. 2015;33: 4301–4308.
25. Kim SR, Pina A, Albert A, McAlpine J, Wolber R, Gilks CB, et al. Does MMR status in endometrial cancer influence response to adjuvant therapy? Gynecol. Oncol. 2018, 151, 76–81.
26. McMeekin DS, Tritchler DL, Cohn DE, Mutch DG, Lankes HA, Geller MA, et al. Clinicopathologic Significance of Mismatch Repair Defects in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol. 2016;34: 3062–3068. Black D, Soslow RA, Levine DA, et al. Clinicopathologic significance of defective DNA mismatch repair in endometrial carcinoma. J Clin Oncol. 2006;24: 1745–1753.
27. Raffone A, Travaglino A, Gabrielli O, Micheli M, Zuccalà V, Bitonti G, et al. Clinical features of ProMisE groups identify different phenotypes of patients with endometrial. Cancer. Arch. Gynecol. Obstet. 2021, 303, 1393–1400.
28. Black D, Soslow RA, Levine DA, Tornos C, Chen SC, Hummer AJ, et al. Clinicopathologic significance of defective DNA mismatch repair in endometrial carcinoma. J Clin Oncol. 2006;24: 1745–1753.
29. Mackay HJ, Gallinger S, Tsao MS, McLachlin CM, Tu D, Keiser K, et al. Prognostic value of microsatellite instability (MSI) and PTEN expression in women with endometrial cancer: results from studies of the NCIC Clinical Trials Group (NCIC CTG). Eur J Cancer. 2010;46: 1365–1373.
30. Cosgrove CM, Cohn DE, Hampel H, Frankel WL, Jones D, McElroy JP, et al. Epigenetic silencing of MLH1 in endometrial cancers is associated with larger tumor volume, increased rate of lymph node positivity and reduced recurrence-free survival. Gynecol Oncol. 2017;146: 588–595.
31. Ruiz I, Martin-Arruti M, Lopez-Lopez E, Garcia-Orad A. Lack of association between deficient mismatch repair expression and outcome in endometrial carcinomas of the endometrioid type. Gynecol Oncol. 2014;134: 20–23.
32. Zighelboim I, Goodfellow PJ, Gao F, Gibb RK, Powell MA, Rader JS, et al. Microsatellite instability and epigenetic inactivation of MLH1 and outcome of patients with endometrial carcinomas of the endometrioid type. J Clin Oncol. 2007;25: 2042–2048.
33. León-Castillo A, de Boer SM, Powell ME, Mileshkin LR, Mackay HJ, Leary A, et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy. J Clin Oncol 2020; 38: 3388–3397.
34. Franchitto A, Pichierri P, Piergentili R, Crescenzi M, Bignami M, Palitti F. The mammalian mismatch repair protein MSH2 is required for correct MRE11 and RAD51 relocalization and for efficient cell cycle arrest induced by ionizing radiation in G2 phase. Oncogene 2003; 22: 2110–2120.
35. Reijnen C, Küsters-Vandevelde HVN, Prinsen CF, Massuger LFAG, Snijders MPML, Kommos S, et al. Mismatch repair deficiency as a predictive marker for response to adjuvant radiotherapy in endometrial cancer. Gynecol Oncol 2019; 154: 124–130.
36. McEachron J, Zhou N, Spencer C, Chatterton C, Shanahan L, Katz J, et al. Adjuvant chemoradiation associated with improved outcomes in patients with microsatellite instability-high advanced endometrial carcinoma. Int J Gynecol Cancer 2021; 31: 203–208.
37. Brown SD, Warren RL, Gibb EA, Martin SD, Spinelli JJ, Nelson BH, et al. Neoantigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Res 2014; 24: 743–750.
38. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2004; 12: 252–264.
39. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature 480: 480-489, 2011.