Potential prognostic significance of p185^HER2 overexpression with loss of PTEN expression in gastric carcinomas

Aims and background: 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. Methods: 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. Results: 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. Conclusions: 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.