Microsatellite instability in endometrial cancer: the role of diagnostic methods and their clinical application. Expert consensus
https://doi.org/10.17650/1994-4098-2022-18-4-138-146
Abstract
Deficient DNA mismatch repair (dMMR) is a rare molecular disorder found in 20-30 % of endometrial tumors. Laboratory identification of dMMR/microsatellite instability (MSI) has a high diagnostic value, since these impairments are considered as biomarkers of endometrial adenocarcinoma. They help to identify patients at high risk of Lynch syndrome, evaluate the disease prognosis, and estimate the efficacy of immune checkpoint inhibitors and their combinations. This review details current concepts of MSI diagnostics and discusses its predictive value in patients with endometrial cancer. It also describes a new diagnostic algorithm for the detection of dMMR and MSI.
Keywords
About the Authors
A. S. TyulyandinaRussian Federation
Alexandra S. Tyulyandina.
23 Kashirskoe Shosse, Moscow 115478; 8/2 Trubetskaya St., Moscow 119991
Competing Interests:
None
E. A. Ulrikh
Russian Federation
68 Leningradskaya St., Pesochniy Settlement, Saint Petersburg 197758; 41 Kirochnaya St., Saint Petersburg 191015
Competing Interests:
None
L. A. Kolomiets
Russian Federation
5 Kooperativnyy Pereulok, Tomsk 634009
Competing Interests:
None
S. E. Krasilnikov
Russian Federation
15 Rechkunovskaya St., Novosibirsk 630055
Competing Interests:
None
A. G. Kedrova
Russian Federation
28 Orekhovyy Bulvar, Moscow 115682; 91 Volokolamskoe Shosse, Moscow 125371
Competing Interests:
None
A. A. Rumyantsev
Russian Federation
23 Kashirskoe Shosse, Moscow 115478
Competing Interests:
None
G. A. Raskin
Russian Federation
7-9 Universitetskaya Naberezhnaya, Saint Petersburg 199034; 43 Karla Marksa St., Pesochnyy, Saint Petersburg 197758
Competing Interests:
None
A. I. Nesterova
Russian Federation
29 Sibirskiy Trakt, Kazan 420029; 18 Kremlevskaya St., Kazan 420008
Competing Interests:
None
M. V. Volkonskiy
Russian Federation
6 Staropetrovskiy Proezd, Moscow 125130
Competing Interests:
None
O. N. Churuksaeva
Russian Federation
5 Kooperativnyy Pereulok, Tomsk 634009
Competing Interests:
None
A. Yu. Goryainova
Russian Federation
146 Dimitrova St., Krasnodar 350040; 4 Mitrofana Sedina St., Krasnodar 350063
Competing Interests:
None
V. V. Zhavoronkova
Russian Federation
78 Zemlyachki St., Volgograd 400138; 12 Ploschad Pavshykh Bortsov, Volgograd 400131
Competing Interests:
None
V. N. Dmitriev
Russian Federation
85 Pobedy St., Belgorod 308015; 1 Kuybysheva St., Belgorod 308010
Competing Interests:
None
S. T. Nazranova
Russian Federation
23 Lermontova St., Nalchik 360051
Competing Interests:
None
A. V. Shkradyuk
Russian Federation
49a Bespalova St., Simferopol 295023
Competing Interests:
None
K. S. Volkova
Russian Federation
50 Solnechnaya St., Samara 443031
Competing Interests:
None
A. I. Arutyunova
Russian Federation
31 Prospekt Kalinina, Pyatigorsk 357502
Competing Interests:
None
S. N. Kunitskaya
Russian Federation
49a Bespalova St., Simferopol 295023
Competing Interests:
None
L. V. Stepura
Russian Federation
153 Shevchenko St., Shakhty 346500
Competing Interests:
None
T. G. Zolotoreva
Russian Federation
50 Solnechnaya St., Samara 443031
Competing Interests:
None
E. B. Shakhnovich
Russian Federation
24 Tsiolkovskogo St., Korolev 141070
Competing Interests:
None
E. V. Ponomareva
Russian Federation
49a Bespalova St., Simferopol 295023
Competing Interests:
None
M. A. Strokova
Russian Federation
49a Bespalova St., Simferopol 295023
Competing Interests:
None
A. S. Danilova
Russian Federation
6 Staropetrovskiy Proezd, Moscow 125130
Competing Interests:
None
E. S. Martynova
Russian Federation
16 1-ya Smolenskaya St., Krasnoyarsk 660133
Competing Interests:
None
References
1. Situtation with cancer care in Russia in 2021. Ed. by A.D. Kaprin, V.V. Starinskiy, A.O. Shakhzadova. Moscow: P.A. Herzen Moscow Oncology Research Institute - a branch of the National Medical Research Radiological Center, Ministry of Health of Russia, 2022. 239 p. (In Russ.)
2. Statistics Adapted from the American Cancer Society's (ACS) Publication, Cancer Facts & Figures 2022, the ACS Website, and the International Agency for Research on Cancer Website. Available at: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html.
3. Travaglino A., Raffone A., Mascolo M. et al. Clear cell endometrial carcinoma and the TCGA classification. Histopathology 2020;76:336-68. DOI: 10.1111/his.13976
4. The Cancer Genome Atlas Research Network. Levine D. Integrated genomic characterization of endometrial carcinoma. Nature 2013;497:67-73. DOI: 10.1038/nature12325
5. Hewish M., Lord C.J., Martin S.A. et al. Mismatch repair deficient colorectal cancer in the era of personalized treatment. Nat Rev Clin Oncol 2010;7(4):197-208.
6. Sinicrope F.A. Lynch syndrome-associated colorectal cancer. N Engl J Med 2018;379(8):764-73.
7. Woods M.O., Williams P., Careen A. et al. A new variant database for mismatch repair genes associated with Lynch syndrome. Hum Mutat 2007;28(7):669-73.
8. Mensenkamp A.R., Vogelaar I.P., van Zelst-Stams W.A. et al. Somatic mutations in MLH1 and MSH2 are a frequent cause of mismatch-repair deficiency in Lynch syndrome-like tumors. Gastroenterology 2014;146(3):643-646.e8.
9. Antelo M., Golubicki M., Roca E. et al. Lynch-like syndrome is as frequent as Lynch syndrome in early-onset nonfamilial nonpolyposis colorectal cancer. Int J Cancer 2019;145(3):705-13.
10. Boland C.R., Goel A. Microsatellite instability in colorectal cancer. Gastroenterology 2010;138(6):2073-2087.e2073.
11. Hernandez J.S. Cost-effectiveness of laboratory testing. Arch Pathol Lab Med 2003;127(4):440-5. DOI: 10.5858/2003-127-0440-COLT
12. Stinton C., Fraser H., Al-Khudairy L. et al. Testing for lynch syndrome in people with endometrial cancer using immunohistochemistry and microsatellite instability-based testing strategies: A systematic review of test accuracy. Gynecol Oncol 2021;160:148-60.
13. Concin N., Matias-Guiu X., Vergote I. et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer 2021;31(1):12-39. DOI: 10.1136/ijgc-2020-002230
14. Makker V., Colombo N., Casado Herraez A. et al. lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med 2022;386(5):437-48. DOI: 10.1056/NEJMoa2108330
15. O'Malley D.M., Bariani G.M., Cassier P.A. et al. Pembrolizumab in patients with microsatellite instability-high advanced endometrial cancer: results from the KEYNOTE-158 study. J Clin Oncol 2022;40(7):752-61. DOI: 10.1200/JCO.21.01874
16. Malapelle U., Parente P., Pepe F. et al. Evaluation of microsatellite instability and mismatch repair status in different solid tumors: a multicenter analysis in a real world setting. Cells 2021;10:1878.
17. Kurnit K.C., Westin S.N., Coleman R.L. Microsatellite instability in endometrial cancer: New purpose for an old test. Cancer 2019;125(13):2154-63. DOI: 10.1002/cncr.32058
18. Alpert L., Pai R.K., Srivastava A. et al. Colorectal carcinomas with isolated loss of PMS2 staining by immunohistochemistry. Arch Pathol Lab Med 2018;142(4):523-8.
19. Pearlman R., Markow M., Knight D. et al. Two-stain immunohistochemical screening for Lynch syndrome in colorectal cancer may fail to detect mismatch repair deficiency. Mod Pathol 2018;31(12):1891-900.
20. Graham R.P., Kerr S.E., Butz M.L. et al. Heterogenous MSH6 loss is a result of microsatellite instability within MSH6 and occurs in sporadic and hereditary colorectal and endometrial carcinomas. Am J Surg Pathol 2015;39(10):1370-6.
21. Olave M.C., Graham R.P. Mismatch repair deficiency: The what, how and why it is important. Genes Chromosomes Cancer 2022;61(6):314-21. DOI: 10.1002/gcc.23015
22. Avila M., Meric-Bernstam F. Next-generation sequencing for the general cancer patient. Clin Adv Hematol Oncol 2019;17(8):447-54.
23. Cho K.R., Cooper K., Croce S. 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-S122.
24. Duraturo F., Liccardo R., De Rosa M., Izzo P. Genetics, diagnosis and treatment of Lynch syndrome: Old lessons and current challenges. Oncol Lett 2019;17(3):3048-54. DOI: 10.3892/ol.2019.9945
25. Favier A., Varinot J., Uzan C. et al. The role of immunohistochemistry markers in endometrial cancer with mismatch repair deficiency: a systematic review. Cancers (Basel) 2022;14(15):3783. DOI: 10.3390/cancers14153783
26. Snowsill T.M., Ryan N.A.J., Crosbie E.J. et al. Cost-effectiveness analysis of reflex testing for Lynch syndrome in women with endometrial cancer in the UK setting. PLoS One 2019;14:e0221419. DOI: 10.1371/journal.pone.0221419
27. Daniels M.S., Urbauer D.L., Zangeneh A. et al. Outcomes of screening endometrial cancer patients for Lynch syndrome by patient-administered checklist. Gynecol Oncol 2013;131:619-23.
28. Oaknin A., Bosse T.J., Creutzberg C.L. et al. Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2022;33(9):860-77. DOI: 10.1016/j.annonc.2022.05.009
29. NCCN Guidelines Version 1.2022 Endometrial Carcinoma. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf.
30. Casey L., Singh N. POLE, MMR, and MSI testing in endometrial cancer: proceedings of the ISGyP companion society session at the USCAP 2020 annual meeting. Int J Gynecol Pathol 2021;40(1):5-16.
Review
For citations:
Tyulyandina A.S., Ulrikh E.A., Kolomiets L.A., Krasilnikov S.E., Kedrova A.G., Rumyantsev A.A., Raskin G.A., Nesterova A.I., Volkonskiy M.V., Churuksaeva O.N., Goryainova A.Yu., Zhavoronkova V.V., Dmitriev V.N., Nazranova S.T., Shkradyuk A.V., Volkova K.S., Arutyunova A.I., Kunitskaya S.N., Stepura L.V., Zolotoreva T.G., Shakhnovich E.B., Ponomareva E.V., Strokova M.A., Danilova A.S., Martynova E.S. Microsatellite instability in endometrial cancer: the role of diagnostic methods and their clinical application. Expert consensus. Tumors of female reproductive system. 2022;18(4):138-146. (In Russ.) https://doi.org/10.17650/1994-4098-2022-18-4-138-146