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.