Supplementary Material for: Loss of Heterozygosity of PTEN (Encoding Phosphate and Tensin Homolog) Associated with Elevated HER2 Expression Is an Adverse Prognostic Indicator in Gastric Cancer

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. © 2014 S. Karger AG, Basel

研究目的：PTEN（磷酸酶与张力蛋白同源基因，phosphate and tensin homolog）是经典抑癌基因，其突变与杂合性缺失（loss of heterozygosity, LOH）可见于多种癌组织。本研究旨在探讨PTEN基因杂合性缺失与HER2（人表皮生长因子受体2）表达阳性及阴性胃癌患者预后的关联。
研究方法：本研究纳入221例经病理确诊为原发性胃癌的新鲜冰冻肿瘤样本，对其PTEN基因的LOH情况进行检测，并将检测结果与患者病理参数及HER2状态进行对比分析。为阐明PTEN基因LOH的生物学作用，本研究采用磷酸化特异性抗体通过免疫组化法检测PI3K/AKT（磷脂酰肌醇3-激酶/蛋白激酶B）通路的激活状态。
研究结果：195例有效病例中，20%的患者（39/195）存在PTEN基因LOH。PTEN基因LOH与血管浸润（39例中25例；p=0.0083）、HER2染色呈可疑阳性至阳性（p=0.0080）以及磷酸化Akt蛋白表达（p=0.0067）显著相关。其中，HER2表达阳性且携带PTEN基因LOH的胃癌患者预后显著更差（p=0.0050）。
研究结论：尽管HER2表达本身并非胃癌的预后影响因子，但HER2表达联合PTEN基因LOH可通过其增殖效应增强胃癌的恶性潜能。© 2014 S. Karger AG, Basel