Prognosis and chemosensitivity of non-colorectal alimentary tract cancers with microsatellite instability

Published:April 06, 2022DOI:



      Data on outcomes of microsatellite instable and/or mismatch repair deficient (dMMR/MSI) digestive non-colorectal tumors are limited.


      To evaluate overall survival (OS) of patients with dMMR/MSI digestive non-colorectal tumor.


      All consecutive patients with a dMMR/MSI digestive non-colorectal tumor were included in this French retrospective multicenter study.


      One hundred and sixteen patients were included with a mean age of 63.6 years and 32.6% with a Lynch syndrome. Most tumors were oesophago-gastric (54.3%) or small bowel (32.8%) adenocarcinomas and at a localized stage at diagnosis (86.7%). In patients with localized tumors and R0 resection, median OS was 134.0 ± 64.2 months. Median disease-free survival (DFS) was 100.3 ± 65.7 months. Considering oesophago-gastric tumors, median DFS was improved when chemotherapy was added to surgery (not reached versus 22.8 ± 10.0 months, p = 0.03). In patients with advanced tumors treated by chemotherapy, median OS was 14.2 ± 1.9 months and median progression-free survival was 7.4 ± 1.6 months.


      dMMR/MSI digestive non-colorectal tumors are mostly diagnosed at a non-metastatic stage with a good prognosis. Advanced dMMR/MSI digestive non-colorectal tumors have a poor prognosis with standard chemotherapy.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Digestive and Liver Disease
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Dedeurwaerdere F.
        • Claes K.B.
        • Van Dorpe J.
        • et al.
        Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer.
        Sci Rep. 2021; 11: 12880
        • Kim J.H.
        • Kang G.H.
        Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer.
        World J Gastroenterol. 2014; 20: 4230-4243
        • Sargent D.J.
        • Marsoni S.
        • Monges G.
        • et al.
        Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer.
        J Clin Oncol. 2010; 28: 3219-3226
        • Ribic C.M.
        • Sargent D.J.
        • Moore M.J.
        • et al.
        Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer.
        N Engl J Med. 2003; 349: 247-257
        • Venderbosch S.
        • Nagtegaal I.D.
        • Maughan T.S.
        • et al.
        Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies.
        Clin Cancer Res. 2014; 20: 5322-5330
        • Tougeron D.
        • Sueur B.
        • Zaanan A.
        • et al.
        Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: an AGEO retrospective multicenter study.
        Int J Cancer. 2020; 147: 285-296
        • Smyth E.C.
        • Wotherspoon A.
        • Peckitt C.
        • et al.
        Mismatch repair deficiency, microsatellite instability, and survival: an exploratory analysis of the medical research council adjuvant gastric infusional chemotherapy (MAGIC) trial.
        JAMA Oncol. 2017; 3: 1197-1203
        • Kim S.Y.
        • Choi Y.Y.
        • An J.Y.
        • et al.
        The benefit of microsatellite instability is attenuated by chemotherapy in stage II and stage III gastric cancer: results from a large cohort with subgroup analyses.
        Int J Cancer. 2015; 137: 819-825
        • Choi Y.Y.
        • Kim H.
        • Shin S.J.
        • et al.
        Microsatellite instability and programmed cell death-ligand 1 expression in stage II/III gastric cancer: post hoc analysis of the CLASSIC randomized controlled study.
        Ann Surg. 2019; 270: 309-316
        • Pietrantonio F.
        • Miceli R.
        • Raimondi A.
        • et al.
        Individual patient data meta-analysis of the value of microsatellite instability as a biomarker in gastric cancer.
        J Clin Oncol. 2019; 37: 3392-3400
        • Aparicio T.
        • Svrcek M.
        • Henriques J.
        • et al.
        Panel gene profiling of small bowel adenocarcinoma, results from the NADEGE prospective cohort.
        Int J Cancer. 2021; 148: 1731-1742
        • Lupinacci R.M.
        • Goloudina A.
        • Buhard O.
        • et al.
        Prevalence of microsatellite instability in intraductal papillary mucinous neoplasms of the pancreas.
        Gastroenterology. 2018; 154: 1061-1065
        • Le D.T.
        • Uram J.N.
        • Wang H.
        • et al.
        PD-1 blockade in tumors with mismatch-repair deficiency.
        N Engl J Med. 2015; 372: 2509-2520
        • Le D.T.
        • Durham J.N.
        • Smith K.N.
        • et al.
        Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.
        Science. 2017; 357: 409-413
        • Kim S.T.
        • Cristescu R.
        • Bass A.J.
        • et al.
        Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer.
        Nat Med. 2018; 24: 1449-1458
        • Marabelle A.
        • Le D.T.
        • Ascierto P.A.
        • et al.
        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. 2020; 38: 1-10
        • Chalabi M.
        • Fanchi L.F.
        • Dijkstra K.K.
        • et al.
        Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers.
        Nat Med. 2020; 26: 566-576
        • D'Asnières De Salins A.G.
        • Tachon G.
        • Cohen R.
        • et al.
        Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer.
        ESMO Open. 2021; 6100120
        • Suraweera N.
        • Duval A.
        • Reperant M.
        • et al.
        Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR.
        Gastroenterology. 2002; 123: 1804-1811
        • Buhard O.
        • Cattaneo F.
        • Wong Y.F.
        • et al.
        Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors.
        J Clin Oncol. 2006; 24: 241-251
        • Genevay M.
        • Benusiglio P.R.
        • Hutter P.
        • Chappuis P.O.
        Lynch syndrome: when pathologist and clinician have the opportunity to reduce the risk of developing cancer.
        Rev Med Suisse. 2011; 7: 1502-1506
        • Beghelli S.
        • de Manzoni G.
        • Barbi S.
        • et al.
        Microsatellite instability in gastric cancer is associated with better prognosis in only stage II cancers.
        Surgery. 2006; 139: 347-356
        • Leite M.
        • Corso G.
        • Sousa S.
        • et al.
        MSI phenotype and MMR alterations in familial and sporadic gastric cancer.
        Int J Cancer. 2011; 128: 1606-1613
        • Al-Batran S.E.
        • Homann N.
        • Pauligk C.
        • et al.
        Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): a multicenter, randomized phase 3 trial.
        J Clin Oncol. 2017; 35: 4004
        • González I.
        • Goyal B.
        • Xia M.D.
        • et al.
        DNA mismatch repair deficiency but not ARID1A loss is associated with prognosis in small intestinal adenocarcinoma.
        Hum Pathol. 2019; 85: 18-26
        • Aparicio T.
        • Henriques J.
        • Manfredi S.
        • et al.
        Small bowel adenocarcinoma: results from a nationwide prospective ARCAD-NADEGE cohort study of 347 patients.
        Int J Cancer. 2020; 147: 967-977
        • Lee H.S.
        • Choi S.I.
        • Lee H.K.
        • et al.
        Distinct clinical features and outcomes of gastric cancers with microsatellite instability.
        Mod Pathol. 2002; 15: 632-640
        • Zaanan A.
        • Costes L.
        • Gauthier M.
        • et al.
        Chemotherapy of advanced small-bowel adenocarcinoma: a multicenter AGEO study.
        Ann Oncol. 2010; 21: 1786-1793