HER-2/neu overexpression is an independent prognostic factor in colorectal cancer

Abstract

The HER-2/neu protein is intimately involved with normal cell proliferation and tissue growth, as it is extensively homologous and is related to the epidermal growth factor receptor. This phenomenon has been most intensively studied in the context of breast carcinoma, in which its amplification and overexpression correlate with the overall course of disease and poor prognoses, and also constitute a predictive factor of poor response to chemotherapy and endocrine therapy. In this study, we investigated the relationships between the expression of HER-2/neu and the clinicopathological characteristics of colorectal cancer, including survival. This study was performed with a view toward the future introduction of Herceptin therapy for colorectal cancer patients. HER-2/neu overexpression and gene amplification were examined via semiquantitative standardized immunohistochemical staining and fluorescence in situ hybridization (FISH) in 137 colorectal cancer patients who underwent curative surgery at the Kangbuk Samsung Hospital. Sixty-five (47.4%) out of 137 patients were determined by immunohistochemistry to have overexpressed HER-2/neu protein. HER-2/neu gene amplification was detected in two patients by FISH. Tumors with HER-2/neu overexpression showed higher postoperative recurrence rate (39.3% vs 14.6%, p=0.013). Tumors with HER-2/neu overexpression were associated with poor 3-year (70.8% vs 83.7%) and 5-year survival rates (55.1% vs 78.3%, p<0.05). Advanced TNM stage, postoperative recurrence, and overexpression of HER-2/neu were found to be independently related to survival by multivariate analysis. HER-2/neu overexpression may constitute an independent prognostic factor in colorectal cancer patients, and patients exhibiting HER-2/neu overexpression might constitute potential candidates for a new adjuvant therapy which involves the use of humanized monoclonal antibodies.