Park Dong Il, Kang Mun Su, Oh Suk Joong, Kim Hong Joo, Cho Yong Kyun, Sohn Chong Il, Jeon Woo Kyu, Kim Byung Ik, Han Won Kon, Kim Hungdai, Ryu Seung Ho, Sepulveda Antonia R
Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Int J Colorectal Dis. 2007 May;22(5):491-7. doi: 10.1007/s00384-006-0192-8. Epub 2006 Sep 1.
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.
HER-2/neu蛋白与正常细胞增殖和组织生长密切相关，因为它与表皮生长因子受体广泛同源且相关。这种现象在乳腺癌研究中最为深入，其扩增和过表达与疾病的整体进程及不良预后相关，也是化疗和内分泌治疗反应不佳的预测因素。在本研究中，我们调查了HER-2/neu表达与结直肠癌临床病理特征（包括生存率）之间的关系。本研究旨在为未来对结直肠癌患者引入赫赛汀治疗提供依据。
通过半定量标准化免疫组织化学染色和荧光原位杂交（FISH）检测了137例在江北三星医院接受根治性手术的结直肠癌患者的HER-2/neu过表达和基因扩增情况。
免疫组织化学检测确定137例患者中有65例（47.4%）HER-2/neu蛋白过表达。FISH检测发现2例患者存在HER-2/neu基因扩增。HER-2/neu过表达的肿瘤术后复发率较高（39.3%对14.6%，p=0.013）。HER-2/neu过表达的肿瘤3年（70.8%对83.7%）和5年生存率较低（55.1%对78.3%，p<0.05）。多因素分析发现，晚期TNM分期、术后复发和HER-2/neu过表达与生存率独立相关。
HER-2/neu过表达可能是结直肠癌患者的独立预后因素，表现出HER-2/neu过表达的患者可能是使用人源化单克隆抗体的新辅助治疗的潜在候选者。
