PT  - JOURNAL ARTICLE
AU  - Gertruda Evaristo
AU  - Amit Katz
AU  - José L. Ramírez-GarcíaLuna
AU  - Marianne S.M. Issac
AU  - Veena Sangwan
AU  - Duc-Vinh Thai
AU  - Nicholas Bertos
AU  - Marie-Christine Guiot
AU  - Sophie Camilleri-Broët
AU  - Victoria Marcus
AU  - Carmen Mueller
AU  - Jonathan Cools-Lartigue
AU  - Pierre O. Fiset
AU  - Lorenzo E. Ferri
TI  - Relation between mismatch repair status, chemoresponse, survival and anatomic location in gastroesophageal adenocarcinoma
AID  - 10.1503/cjs.017021
DP  - 2023 Feb 15
TA  - Canadian Journal of Surgery
PG  - E79--E87
VI  - 66
IP  - 1
4099  - http://canjsurg.ca/content/66/1/E79.short
4100  - http://canjsurg.ca/content/66/1/E79.full
SO  - CAN J SURG2023 Feb 15; 66
AB  - Background: It has recently been reported that mismatch repair (MMR) status and microsatellite instability (MSI) status in gastroesophageal carcinomas predict surgical, chemotherapeutic and immunotherapeutic outcomes; however, there is extensive variability in the reported incidence and clinical implications of MMR/MSI status in gastroesophaegal adenocarcinomas. We characterized a Canadian surgical patient cohort with respect to MMR status, clinicopathologic correlates and anatomic tumour location.Methods: We investigated MMR and BRAF V600E status of gastroesophaegal adenocarcinomas in patients who underwent gastrectomy or esophagectomy with extended (D2) lymphadenectomy at a single centre between 2011 and 2019. We correlated patterns of MMR expression in the overall cohort and in anatomic location–defined subgroups with treatment response and overall survival using multivariate analysis.Results: In all, 226 cases of gastroesophaegal adenocarcinoma (63 esophageal, 98 gastroesophageal junctional and 65 gastric) were included. The MMR-deficient (dMMR) immunophenotype was found in 28 tumours (12.3%) (15 junctional [15.3%], 13 gastric [20.0%] and none of the esophageal). The majority (25 [89%]) of dMMR cases showed MLH1/PMS2 loss without concurrent BRAF V600E mutation. Two MSH2/ MSH6-deficient gastric tumours and 1 MSH6-deficient junctional tumour were detected. The pathologic response to preoperative chemotherapy was comparable in the dMMR and MMR-proficient (pMMR) cohorts. However, dMMR status was associated with significantly longer median overall survival than pMMR status (5.8 yr v. 2.4 yr, hazard ratio [HR] 1.91, 95% confidence interval [CI] 1.06–3.46), particularly in junctional tumours (4.6 yr v. 1.9 yr, HR 2.97, 95% CI 1.27–6.94).Conclusion: Our study shows that MMR status has at least prognostic value, which supports the need for biomarker testing in gastroesophageal adenocarcinomas, including junctional adenocarcinomas. This highlights the clinical significance of determining the MMR status in all adenocarcinomas of the upper gastrointestinal tract. Response to induction chemotherapy, however, was not influenced by MMR status.