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01-01-2017 | Original Article

Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy

Authors: Riccardo Giampieri, Elena Maccaroni, Alessandra Mandolesi, Michela Del Prete, Kalliopi Andrikou, Luca Faloppi, Alessandro Bittoni, Maristella Bianconi, Marina Scarpelli, Raffaella Bracci, Mario Scartozzi, Stefano Cascinu

Published in: Gastric Cancer | Issue 1/2017

Abstract

Introduction

The microsatellite-instable gastric cancer subtype, because of its supposed high antigenic potential, is a promising candidate for immunotherapy. We analyzed if the presence of a defective mismatch repair (MMR) system is associated with other markers of immune response and their relationship with outcome in advanced gastric cancer patients.

Methods

We analyzed the relationship between clinical outcome and MMR status, the presence of tumor-infiltrating lymphocytes (TIL), lymphocytosis, and neutrophil-to-lymphocyte ratio (NLR) in metastatic gastric cancer patients treated with a chemotherapy doublet in the first-line setting. Other stratification factors were sex, age, Eastern Cooperative Oncology Group performance status, adjuvant/neoadjuvant chemotherapy, metastatic sites, and histotype.

Results

One hundred three patients were eligible for analysis. Defective MMR was found in 15 patients (14 %), TILs were found in 18 patients (17 %), lymphocytosis was found in 24 patients (23 %), and high NLR was found in 75 patients (72 %). Significant correlations were found between defective MMR and TIL positivity (p = 0.0004), between defective MMR and lymphocytosis (p = 0.0062), between defective MMR and low NLR (p = 0.000069), and between TIL positivity and lymphocytosis (p = 0.000147). All factors had a statistically significant impact on overall survival, although on multivariate analysis only defective MMR (p = 0.0001) and TIL positivity (p = 0.0192) maintained their independent prognostic role. Similar results were observed for progression-free survival, with defective MMR (p = 0.0001) and TIL positivity (p = 0.0195) maintaining their prognostic role on multivariate analysis.

Conclusions

Our analysis confirms the favorable prognosis of metastatic gastric cancer patients with a defective MMR system and suggests that expression of TILs might also be linked to better outcome. Because of the correlation between defective MMR status and measures of immune system activity, this group of patients would be the best candidates for novel immunotherapy-based therapies.

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Title: Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy
Authors: Riccardo Giampieri
Elena Maccaroni
Alessandra Mandolesi
Michela Del Prete
Kalliopi Andrikou
Luca Faloppi
Alessandro Bittoni
Maristella Bianconi
Marina Scarpelli
Raffaella Bracci
Mario Scartozzi
Stefano Cascinu
Publication date: 01-01-2017
Publisher: Springer Japan
Published in: Gastric Cancer / Issue 1/2017
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI: https://doi.org/10.1007/s10120-016-0594-4

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Abstract

Introduction

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Conclusions

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