Autophagy-related Prognostic Signature in HER2 Positive Gastric Carcinomas

免疫组织化学 单变量分析 单变量 阶段(地层学) 内科学 癌症 肿瘤科 多元分析 医学 自噬 队列 病理 生物 胃肠病学 多元统计 细胞凋亡 统计 古生物学 生物化学 数学
作者
Antonio Ieni,Cristina Pizzimenti,Giuseppe Giuffrè,Rosario Alberto Caruso,Giovanni Tuccari
出处
期刊:Current Molecular Medicine [Bentham Science Publishers]
卷期号:22 (9): 809-818 被引量:3
标识
DOI:10.2174/1566524021666211123093532
摘要

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.
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