胃和胃食管交界部癌中 HSP90 与 Her2 的相关性。

Association between HSP90 and Her2 in gastric and gastroesophageal carcinomas.

机构信息

Institute of Pathology, University of Bern, Bern, Switzerland.

出版信息

PLoS One. 2013 Jul 11;8(7):e69098. doi: 10.1371/journal.pone.0069098. Print 2013.

DOI:10.1371/journal.pone.0069098

PMID:23874879

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3708885/

Abstract

BACKGROUND

Her2 expression and amplification occurs in a significant subset of gastro-esophageal carcinomas. Her2 is a client protein of molecular chaperones, e.g. heat shock protein (HSP) 90, rendering targeted therapies against Her2/HSP90 an interesting approach. This study aimed to investigate the role and relationship of Her2 and HSP90 in gastric and gastro-esophageal adenocarcinomas.

MATERIAL AND METHODS

Immunohistochemical determination of HSP90 and Her2 expression was performed on 347 primary resected tumors. Her2 amplification was additionally determined by fluorescence in situ hybridization for all cases. Expression and amplification results were correlated with pathologic parameters (UICC pTNM category, tumor grading) and survival.

RESULTS

Elevated Her2 copy numbers were observed in 87 tumors, 21 of them showing amplification. 174 tumors showed Her2 immunoreactivity/expression. HSP 90 immunoreactivity was found in 125 tumors. There was no difference between gastric carcinomas and carcinomas of the gastroesophageal junction regarding Her2 or HSP90. Both high HSP90 and Her2 expression/amplification were associated with earlier tumor stages (p<0.01), absence of lymph node metastases (p<0.02) and Laurens intestinal type (p<0.001). HSP90 correlated with Her2 expression and amplification (p<0.001 each). Expressions of HSP90 and Her2, but not Her2 amplification were associated with better prognosis (p=0.02; p=0.004; p=0.802). Moreover, Her2 expression was an independent prognostic factor for overall survival in the subgroup of gastric carcinoma patients (p=0.014) besides pT category, pN category and distant metastases.

CONCLUSION

Her2 expression and gene amplification occurred in a significant subset of cases. Our results suggest a favorable prognostic impact of Her2 expression. This warrants further investigations regarding the significance of Her2 non-amplified tumors showing Her2 immunoreactivity and the definition of Her2 status in gastric cancers. Moreover, the correlation of Her2 expression with the expression of Her2 chaperoning HSP90 may indicate a synergistic regulation. Targeting HSP90 with or without Her2 may offer additional therapeutic options for gastric carcinoma treatment.

摘要

背景

Her2 表达和扩增发生在相当一部分胃食管腺癌中。Her2 是分子伴侣，如热休克蛋白（HSP）90 的客户蛋白，针对 Her2/HSP90 的靶向治疗是一种很有前途的方法。本研究旨在探讨 Her2 和 HSP90 在胃和胃食管腺癌中的作用和关系。

材料和方法

对 347 例原发性切除肿瘤进行 HSP90 和 Her2 表达的免疫组织化学测定。对所有病例均采用荧光原位杂交法检测 Her2 扩增。表达和扩增结果与病理参数（UICC pTNM 分期、肿瘤分级）和生存相关。

结果

在 87 例肿瘤中观察到 Her2 拷贝数升高，其中 21 例为扩增。174 例肿瘤显示 Her2 免疫反应/表达。125 例肿瘤存在 HSP90 免疫反应。胃腺癌和胃食管交界处腺癌在 Her2 或 HSP90 方面无差异。高 HSP90 和 Her2 表达/扩增均与较早的肿瘤分期（p<0.01）、无淋巴结转移（p<0.02）和 Laurens 肠型（p<0.001）相关。HSP90 与 Her2 表达和扩增相关（均为 p<0.001）。HSP90 和 Her2 的表达，而不是 Her2 扩增，与较好的预后相关（p=0.02；p=0.004；p=0.802）。此外，在胃腺癌患者亚组中，Her2 表达是总生存的独立预后因素（p=0.014），除了 pT 分期、pN 分期和远处转移外。

结论

Her2 表达和基因扩增发生在相当一部分病例中。我们的结果表明 Her2 表达具有良好的预后影响。这需要进一步研究 Her2 免疫反应性非扩增肿瘤的意义以及胃腺癌中 Her2 状态的定义。此外，Her2 表达与 Her2 伴侣 HSP90 的表达相关可能表明存在协同调节。针对 HSP90 或不针对 Her2 可能为胃癌治疗提供额外的治疗选择。