HER2 阳性胃癌的自噬相关预后标志物。

Autophagy-related Prognostic Signature in HER2 Positive Gastric Carcinomas.

机构信息

Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", Section of Pathology, University of Messina, Messina, Italy.

出版信息

Curr Mol Med. 2022;22(9):809-818. doi: 10.2174/1566524021666211123093532.

DOI:10.2174/1566524021666211123093532

PMID:34814818

Abstract

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.

摘要

背景

自噬相关蛋白（ATGs）的免疫组化分析最近已应用于人类病理学研究，以研究分化和癌症进展。本研究的目的是通过五种 ATG 抗血清（Beclin-1、LC3A/B、p62、ULK-1 和 AMBRA-1）分析一组胃癌（GC），同时评估它们与临床病理参数、HER2 状态和患者最终结局的可能关系。

方法

使用 Masuda 标准对 123 例 GC 进行了 ATG 抗血清分析，该标准定义了至少有两种蛋白表达阳性的病例为阳性。

结果

自噬的免疫组化特征（A-IHC）总体为 49.59%。A-IHC 的百分比范围从 31%的非黏附性癌到 56%的腺癌。每个 ATG 免疫标志物的性能对于 LC3A/B、Beclin-1 和 p62 的敏感性、特异性和效率都有很高的数值。在 GC 的单因素分析中，分级、分期、Ki67 表达、HER2 状态以及 A-IHC 似乎都是具有高 p 值（p<0.001）的相关参数。最后，在多因素分析中，HER2 状态、分期和 A-IHC 是独立的预后变量。在生存曲线的比较中，免疫组化 A-IHC 阳性的 GC 病例的生存时间更短，结局更差。