Testing for deficient mismatch repair and microsatellite instability
Tóm tắt
Testing to detect mismatch repair deficiency (dMMR) and high-grade microsatellite instability (MSI-H) has become an integral part of the routine diagnostic workup for colorectal cancer (CRC). While MSI was initially considered to be a possible indicator of a hereditary disposition to cancer (Lynch syndrome, LS), today the prediction of the therapy response to immune checkpoint inhibitors (ICI) is in the foreground. Corresponding recommendations and testing algorithms are available for use in primary diagnosis (reviewed in: Rüschoff et al. 2021). Given the increasing importance for routine use and the expanding indication spectrum of ICI therapies for non-CRCs, such as endometrial, small intestinal, gastric, and biliary tract cancers, an updated review of dMMR/MSI testing is presented. The focus is on the challenges in the assessment of immunohistochemical stains and the value of PCR-based procedures, considering the expanded ICI indication spectrum. A practice-oriented flowchart for everyday diagnostic decision-making is provided that considers new data on the frequency and type of discordances between MMR-IHC and MSI-PCR findings, and the possible role of Next Generation Sequencing in clarifying them. Reference is made to the significance of systematic quality assurance measures (e.g., QuIP MSI portal and multicenter proficiency testing), including regular continued training and education.
Tài liệu tham khảo
André T, KEYNOTE-177 Investigators et al (2020) Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med 383(23):2207–2218
AWMF (2022) S3-Leitlinie Endometriumkarzinom (Langversion 2.0-Registernummer: 032/034-OL)
Bao F et al (2010) Neoadjuvant therapy induces loss of MSH6 expression in colorectal carcinoma. Am J Surg Pathol 34:1798–1804
Bartley AN, Mills AM, Konnick E et al (2022) Mismatch repair and microsatellite instability testing for immune checkpoint inhibitor therapy: guideline from the college of American pathologists in collaboration with the association for molecular pathology and fight colorectal cancer. Arch Pathol Lab Med 146:1194–1210
Dietmaier W, Büttner R, Rüschoff J (2019) Mikrosatelliteninstabilität: Aktueller Überblick über Methoden und Anwendungen. Pathologe 40(3):313–327
Dominguez-Valentin M et al (2020) Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants. Genet Med 22:15–25
Fadhil W, Ilyas M (2012) Immunostaining for mismatch repair (MMR) protein expression in colorectal cancer is better and easier to interpret when performed on diagnostic biopsies. Histopathology 60:653–655
Frankel WL et al (2019) Lynch Syndrome. WHO classification of tumors. Digestive system tumours. WHO, IARC, pp 515–521
Hechtman JF, Rana S, Middha S et al (2020) Retained mismatch repair protein expression occurs in approximately 6 % of microsatellite instability-high cancers and is associated with missense mutations in mismatch repair genes. Mod Pathol 33:871–879
Jaffrelot M, Farés N, Brunac AC et al (2022) An unusual phenotype occurs in 15 % of mismatch repair-deficient tumors and is associated with non-colorectal cancers and genetic syndromes. Mod Pathol 35:427–437
Kang SY, Kim DG, Ahn S et al (2022) Comparative analysis of microsatellite instability by next-generation sequencing, MSI PCR and MMR immunohistochemistry in 1942 solid cancers. Pathol Res Pract 233:153874
Kloth M, Ruesseler V, Engel C et al (2016) Activating ERBB2/HER2 mutations indicate susceptibility to pan-HER inhibitors in Lynch and Lynch-like colorectal cancer. Gut 65:1296–1305
Krüger S, Kinzel M, Walldorf C (2008) Homozygous PMS2 germline mutations in two families with early-onset haematological malignancy, brain tumours, HNPCC-associated tumours, and signs of neurofibromatosis type 1. Eur J Hum Genet 16:62–72
Le DT, Uram JN, Wang H et al (2015) PD‑1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520
Li Z, Cheng B, Liu S et al (2022) Non-classical phenotypes of mismatch repair deficiency and microsatellite instability in primary and metastatic tumors at different sites in Lynch syndrome. Front Oncol 12:1004469
Luchini C, Bibeau F, Ligtenberg MJL et al (2019) 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 30:1232–1243
Ma X, Dong L, Liu X, Ou K, Yang L (2022) POLE/POLD1 mutation and tumor immunotherapy. J Exp Clin Cancer Res 41:216
Malapelle U, Parente P, Pepe F et al (2020) Impact of pre-analytical factors on MSI test accuracy in mucinous colorectal adenocarcinoma: a multi-assay concordance study. Cells 9(9):2019
Marabelle A, Le DT, Ascierto PA et al (2020) Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol 38:1–10
NCCN (2022) https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf. Zugegriffen: 3. März 2023
Oaknin A, Gilbert L, Tinker AV et al (2020) LBA36—safety and antitumor activity of dostarlimab in patients (pts) with advanced or recurrent DNA mismatch repair deficient (dMMR) or proficient (MMRp) endometrial cancer (EC): results from Garnet. Ann Oncol 31:S1142–S1215
Rüschoff J, Baretton G, Bläker H et al (2021) MSI-Testung : Was ist neu? Was ist zu beachten? Pathologe 42:414–423
Salem ME, Bodor JN, Puccini A et al (2020) Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors. Int J Cancer 147:2948–2956
Samaison L, Uguen A (2022) Idylla MSI test combined with immunohistochemistry is a valuable and cost effective strategy to search for microsatellite instable tumors of noncolorectal origin. Pathol Int 72(4):234–241
Schöniger S, Rüschoff J (2022) Mismatch repair deficiency and microsatellite instability. Encyclopedia 2:1559–1576. https://doi.org/10.3390/encyclopedia2030106
Shia J (2021) The diversity of tumours with microsatellite instability: molecular mechanisms and impact upon microsatellite instability testing and mismatch repair protein immunohistochemistry. Histopathology 78:485–497
Siemanowski J, Schömig-Markiefka B, Buhl T et al (2021) Managing difficulties of microsatellite instability testing in endometrial cancer-limitations and advantages of four different PCR based approaches. Cancers 13(6):1268. https://doi.org/10.3390/cancers13061268
Smithgall MC, Remotti H, Hsiao SJ et al (2022) Investigation of discrepant mismatch repair immunohistochemistry and microsatellite instability polymerase chain reaction test results for gynecologic cancers using next-generation sequencing. Hum Pathol 119:41–50
Stelloo E, Jansen AML, Osse EM et al (2017) Practical guidance for mismatch repair-deficiency testing in endometrial cancer. Ann Oncol 28:96–102
Ukkola I, Nummela P, Pasanen A et al (2021) Detection of microsatellite instability with Idylla MSI assay in colorectal and endometrial cancer. Virchows Arch 479:471–479
Wang C, Zhang L, Vakiani E, Shia J (2022) Detecting mismatch repair deficiency in solid neoplasms: immunohistochemistry, microsatellite instability, or both? Mod Pathol 35:1515–1528
Win AK, Jenkins MA, Dowty JG et al (2017) Prevalence and penetrance of major genes and polygenes for colorectal cancer. Cancer Epidemiol Biomarkers Prev 26:404–412
Yang RK, Chen H, Roy-Chowdhuri S et al (2022) Clinical testing for mismatch repair in neoplasms using multiple laboratory methods. Cancers (Basel) 14(19):4550
Yoshino T, Pentheroudakis G, Mishima S et al (2020) JSCOESMO-ASCO-JSMO-TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions. Ann Oncol 31:861–872
Zhang Q, Young GQ, Yang Z (2020) Pure discrete punctate nuclear staining pattern for MLH1 protein does not represent intact nuclear expression. Int J Surg Pathol 28:146–152