Impact of mismatch repair deficiency on tumour regression grade after neoadjuvant chemotherapy in localized gastroesophageal adenocarcinoma

Maximilien Heran; Florence Renaud; Christophe Louvet; Guillaume Piessen; Thibault Voron; Marine Lefèvre; Olivier Dubreuil; Thierry André; Magali Svrcek; Romain Cohen

doi:10.1016/j.dld.2022.06.009

Impact of mismatch repair deficiency on tumour regression grade after neoadjuvant chemotherapy in localized gastroesophageal adenocarcinoma

Dig Liver Dis. 2023 Feb;55(2):276-282. doi: 10.1016/j.dld.2022.06.009. Epub 2022 Jun 29.

Authors

Affiliations

¹ Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, 184 rue du Faubourg Saint-Antoine, Paris 75012, France. Electronic address: [email protected].
² Department of Pathology, Claude Huriez University Hospital, Lille, France.
³ Department of Medical Oncology, Institut Mutualiste Montsouris, Paris, France.
⁴ CHU Lille, Department of Digestive and Oncological Surgery, Claude Huriez Hospital, Lille F-59000, France; CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, University Lille, Lille F-59000, France.
⁵ Department of Digestive Surgery, Saint-Antoine Hospital, AP-HP, Sorbonne University, Paris, France.
⁶ Department of Pathology, Institut Mutualiste Montsouris, Paris, France.
⁷ Department of Digestive Oncology, Groupe Hospitalier Diaconesses Croix Saint Simon, Paris, France.
⁸ Department of Medical Oncology, Saint-Antoine Hospital, AP-HP; SIRIC CURAMUS, INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Sorbonne University, Paris, France.
⁹ Department of Pathology, Saint-Antoine Hospital, AP-HP; SIRIC CURAMUS, INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Sorbonne University, Paris, France.

PMID: 35780065
DOI: 10.1016/j.dld.2022.06.009

Abstract

Background: The use of neoadjuvant chemotherapy (NAC) in patients with mismatch repair (MMR) deficient (dMMR) localized gastric and oeso-gastric junction (OGJ) adenocarcinoma is subject of debate. Histological response assessment might help to better evaluate the impact of dMMR on response to NAC.

Methods: Patients with localized gastric/OGJ adenocarcinoma resected after NAC were retrospectively identified. MMR protein expression status was assessed by immunohistochemistry. The primary objective was the frequency of histological responders to NAC defined by tumour regression grade (TRG) using Mandard's (TRG1-2) and Becker's (TRG1) classifications, according to the MMR status.

Results: In total, 247 patients with 43 dMMR and 204 pMMR gastric/OGJ adenocarcinoma were identified. Among dMMR tumours, 18 (42%) arose from the OGJ. Histological response (Becker TRG1-2) was observed for 28% and 35% of dMMR and pMMR tumours, respectively (p = 0.35). Similar results were observed with Mandard classification. With a median follow-up of 37.5 months, median disease-free and overall survival were not reached for the dMMR group.

Conclusion: Histological response after NAC in patients with localized dMMR gastric/OGJ adenocarcinoma is not statistically different to those with pMMR tumours. This study provides additional data for the discussion about avoiding NAC in patients with dMMR gastric/OGJ adenocarcinomas.

Keywords: Biomarker; Gastric cancer; Localized cancer; Microsatellite instability; Mismatch repair.

MeSH terms

Adenocarcinoma* / drug therapy
Adenocarcinoma* / genetics
Colorectal Neoplasms* / pathology
DNA Mismatch Repair / genetics
Humans
Neoadjuvant Therapy
Retrospective Studies
Stomach Neoplasms* / drug therapy
Stomach Neoplasms* / genetics
Stomach Neoplasms* / pathology

Supplementary concepts

Turcot syndrome