Hirsch Fred R, Franklin Wilbur A, Veve Robert, Varella-Garcia Marileila, Bunn Paul A
Lung Cancer Program, Department of Pathology, University of Colorado Cancer Center, Denver, CO 80262, USA.
Semin Oncol. 2002 Feb;29(1 Suppl 4):51-8. doi: 10.1053/sonc.2002.31523.
Despite intensive treatment efforts, the prognosis for lung cancer is very poor; less than 15% of patients survive 5 years. Trastuzumab, a monoclonal antibody targeting the HER2/neu protein receptor, is effective in the treatment of metastatic breast cancer and may be useful in the treatment of non-small cell lung cancer (NSCLC). Using the HercepTest (Dako; Carpenteria, CA), 25% of NSCLC show 2+ or greater HER2/neu expression, but only 6% to 8% of NSCLC tumors have 3+ overexpression. Positive HER2/neu expression is most often seen in adenocarcinomas compared with squamous cell carcinomas or large cell carcinomas, and is rarely seen in small cell lung cancer. As determined by fluorescence in situ hybridization analysis, the high degree of HER2/neu gene expression and gene amplification seen in breast cancer is lower in NSCLC. Polysomy is the cause of increased HER2/neu expression in most NSCLC. Prospective clinical studies with trastuzumab in lung cancer are ongoing. Future studies in NSCLC need to include immunohistochemistry and fluorescence in situ hybridization analysis to determine the method of choice for evaluating clinically relevant HER2/neu-positive tumors.
尽管进行了积极的治疗，但肺癌的预后非常差；不到15%的患者能存活5年。曲妥珠单抗是一种靶向HER2/neu蛋白受体的单克隆抗体，对转移性乳腺癌有效，可能对非小细胞肺癌（NSCLC）的治疗也有用。使用HercepTest（达科公司；加利福尼亚州卡平特里亚）检测，25%的NSCLC显示HER2/neu表达为2+或更高，但只有6%至8%的NSCLC肿瘤有3+过表达。与鳞状细胞癌或大细胞癌相比，HER2/neu阳性表达最常见于腺癌，在小细胞肺癌中很少见。通过荧光原位杂交分析确定，NSCLC中HER2/neu基因的高表达和基因扩增程度低于乳腺癌。多体性是大多数NSCLC中HER2/neu表达增加的原因。关于曲妥珠单抗治疗肺癌的前瞻性临床研究正在进行。未来对NSCLC的研究需要包括免疫组织化学和荧光原位杂交分析，以确定评估临床上相关的HER2/neu阳性肿瘤的首选方法。
