Im Seock-Ah, Lee Kyung Eun, Nam Eunmi, Kim Do Yeun, Lee Joo-Ho, Han Ho-Seong, Seoh Ju-Young, Park Hae-Young, Cho Min-Sun, Han Woon Sup, Lee Soon Nam
Section of Oncology/Hematology, Department of Internal Medicine, Seoul National University, College of Medicine, 28 Yongondong Chongnogu, Seoul, 110-744, Korea.
Tumori. 2005 Nov-Dec;91(6):513-21. doi: 10.1177/030089160509100612.
The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185(HER2)) that has partial homology with the epidermal growth factor receptor and shares intrinsic tyrosine kinase activity. The phosphatase and tensin homolog mutated on chromosome ten (PTEN) gene product is a protein tyrosine phosphatase that participates in modulating the phosphoinositide 3-kinase pathway which has antagonizing activity to protein tyrosine kinase. The authors investigated the correlation between clinicopathologic variables including survival and the overexpression of the p185(HER2) with loss of PTEN expression in gastric adenocarcinoma patients.
The protein expression of p185(HER2) and PTEN was examined by immunohistochemical stain in paraffin-embedded tissues of 94 (M:F, 52:42) gastric adenocarcinoma patients by using monoclonal antibody, and the results were related to clinicopathological variables and survival.
p185(HER2) overexpression correlated positively with lymph node metastasis, distant metastasis, AJCC classification, higher relapse rate. Patients with overexpression of p185(HER2) were found to have significantly lower disease-free survival (P = 0.003) and overall survival (P = 0.0004). Loss of PTEN expression correlated positively with depth of invasion (T stage) and was more frequent in the advanced stage. The patient group with p185(HER2) overexpression and loss of PTEN expression showed significantly shorter disease-free and overall survival (P = 0.03, P = 0.01) than the other groups.
Our observations suggest potential prognostic significance of p185(HER2) overexpression with PTEN loss in gastric adenocarcinoma patients. This opens up the possibility of considering p185(HER2)and PTEN as a therapeutic target in gastric cancer.
HER2基因编码一种185-kd跨膜糖蛋白受体（p185(HER2)），其与表皮生长因子受体有部分同源性，并具有内在酪氨酸激酶活性。10号染色体上磷酸酶和张力蛋白同源物（PTEN）基因产物是一种蛋白酪氨酸磷酸酶，参与调节对蛋白酪氨酸激酶具有拮抗活性的磷酸肌醇3激酶途径。作者研究了包括生存情况在内的临床病理变量与胃腺癌患者中p185(HER2)过表达伴PTEN表达缺失之间的相关性。
采用单克隆抗体，通过免疫组织化学染色检测94例（男:女，52:42）胃腺癌患者石蜡包埋组织中p185(HER2)和PTEN的蛋白表达，并将结果与临床病理变量及生存情况相关联。
p185(HER2)过表达与淋巴结转移、远处转移、美国癌症联合委员会（AJCC）分类、较高复发率呈正相关。p185(HER2)过表达的患者无病生存期（P = 0.003）和总生存期（P = 0.0004）显著更低。PTEN表达缺失与浸润深度（T分期）呈正相关，且在晚期更常见。p185(HER2)过表达且PTEN表达缺失的患者组无病生存期和总生存期显著短于其他组（P = 0.03，P = 0.01）。
我们的观察结果提示胃腺癌患者中p185(HER2)过表达伴PTEN缺失具有潜在的预后意义。这为将p185(HER2)和PTEN作为胃癌治疗靶点开辟了可能性。
