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Current Molecular Medicine


ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Autophagy-related Prognostic Signature in HER2 Positive Gastric Carcinomas

Author(s): Antonio Ieni*, Cristina Pizzimenti, Giuseppe Giuffrè, Rosario Alberto Caruso and Giovanni Tuccari

Volume 22, Issue 9, 2022

Published on: 11 January, 2022

Page: [809 - 818] Pages: 10

DOI: 10.2174/1566524021666211123093532

Price: $65


Background: The immunohistochemical analysis of autophagy-related proteins (ATGs) has been recently applied in human pathology to study differentiation and cancer progression. The aim of the present study is to analyze a cohort of gastric carcinomas (GC) by five ATG antisera (Beclin-1, LC3A/B, p62, ULK-1 and AMBRA-1), also evaluating their possible relationship with clinicopathological parameters, HER2 status and final outcome of patients.

Methods: A cohort of 123 GCs has been studied by ATG antisera utilizing Masuda's criteria that define positive cases in which at least two out of five protein expressions were documented.

Results: The immunohistochemical signature for autophagy (A-IHC) was 49.59% as a whole. The percentage of A-IHC ranged from 31% for poorly cohesive carcinomas to 56% for adenocarcinomas. The performance of each ATG immunomarker documented high values for sensitivity, specificity and efficiency for LC3A/B, Beclin-1 and p62. In univariate analysis of GC, grade, stage, Ki67 expression, HER2 status as well as A-IHC appeared as emerged as relevant parameters with a high p-value (p < 0.001). Finally, in multivariate analysis, HER2 status, stage and A-IHC emerged as independent prognostic variables. In the comparison of survival curves, GC cases immunoreactive for A-IHC exhibited a shorter survival with a worse outcome.

Conclusions: We have hypothesized that A-IHC could represent an additional morphological tool to provide prognostic elements in order to identify patients affected by aggressive with shorter survival and worse outcome.

Keywords: Autophagy, immunohistochemistry, gastric cancer, HER2 status, prognosis, cancer treatment.

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