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与HER2表达升高相关的PTEN（编码磷酸酶和张力蛋白同源物）杂合性缺失是胃癌的不良预后指标。

Loss of heterozygosity of PTEN (encoding phosphate and tensin homolog) associated with elevated HER2 expression is an adverse prognostic indicator in gastric cancer.

作者信息

Zaitsu Yoko, Oki Eiji, Ando Koji, Ida Satoshi, Kimura Yasue, Saeki Hiroshi, Morita Masaru, Hirahashi Minako, Oda Yoshinao, Maehara Yoshihiko

机构信息

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Oncology. 2015;88(3):189-94. doi: 10.1159/000368984. Epub 2014 Nov 27.

DOI:10.1159/000368984

PMID:25472613

Abstract

OBJECTIVE

PTEN (the encoding phosphate and tensin homolog) is a well-known cancer suppressor gene and its mutation and loss of heterozygosity (LOH) occurs in various types of carcinomas. This study aimed to examine the association between LOH of PTEN and prognosis in HER2-expressing and nonexpressing gastric cancer patients.

METHODS

Fresh-frozen tumor samples of 221 gastric cancer patients with a primary diagnosis of gastric carcinoma were examined for LOH of PTEN. The results were compared with pathological parameters and the HER2 status. To elucidate the role of LOH of PTEN, the activation of the PI3K/AKT pathway was examined immunohistochemically using a phosphorylation-specific antibody.

RESULTS

LOH of PTEN was observed in 20% of the patients (39 of 195 cases). LOH of PTEN was associated with vascular involvement (25 of 39 cases; p = 0.0083), equivocal to positive staining for HER2 (p = 0.0080), and phospho-Akt expression (p = 0.0067). Patients with HER2-expressing gastric cancer with LOH of PTEN had a significantly worse prognosis (p = 0.0050).

CONCLUSIONS

Although HER2 expression itself was not a prognostic factor, the combination of HER2 expression and LOH of PTEN exacerbates the malignant potential of gastric cancer through its proliferative function.

摘要

目的

PTEN（编码磷酸酶和张力蛋白同源物）是一种著名的抑癌基因，其突变和杂合性缺失（LOH）见于多种类型的癌。本研究旨在检测PTEN基因杂合性缺失与HER2表达及未表达的胃癌患者预后之间的关联。

方法

对221例初诊为胃癌的患者的新鲜冷冻肿瘤样本进行PTEN基因杂合性缺失检测。将结果与病理参数及HER2状态进行比较。为阐明PTEN基因杂合性缺失的作用，使用磷酸化特异性抗体通过免疫组织化学检测PI3K/AKT通路的激活情况。

结果

20%的患者（195例中的39例）检测到PTEN基因杂合性缺失。PTEN基因杂合性缺失与血管侵犯相关（39例中的25例；p = 0.0083），HER2染色呈可疑阳性（p = 0.0080），以及磷酸化Akt表达（p = 0.0067）。PTEN基因杂合性缺失的HER2表达阳性胃癌患者预后明显更差（p = 0.0050）。