Haneda Hiroshi, Sasaki Hidefumi, Shimizu Shigeki, Endo Katsuhiko, Suzuki Eriko, Yukiue Haruhiro, Kobayashi Yoshihiro, Yano Motoki, Fujii Yoshitaka
Department of Surgery II, Nagoya City University Medical School, Japan.
Lung Cancer. 2006 Apr;52(1):47-52. doi: 10.1016/j.lungcan.2005.12.005. Epub 2006 Feb 28.
Epidermal growth factor receptor (EGFR) gene mutations are frequently detected in lung cancer, especially in adenocarcinoma, in females, and non-smoking patients. EGFR mutations are closely associated with clinical response to EGFR tyrosine kinase inhibitor. Bronchioloalveolar carcinoma (BAC) appearance is a good predictor of response to this agent. Noguchi et al. subdivided small peripheral adenocarcinoma of the lung into two groups. One group was characterized with tumor cell growth replacing the normal alveolar cells with varying degree of fibrosis (types A-C), and the other shows non-replacing and destructive growth (types D-F). Using probes for the 13 mutations which have been previously described, we have genotyped the EGFR gene status in surgically resected atypical adenomatous hyperplasias (AAH) and small peripheral adenocarcinomas up to 2 cm in diameter using TaqMan PCR assay. In 95 small-sized adenocarcinomas, the EGFR mutations were detected in 37 patients (38.9%), and no mutations were found in five AAHs. In small peripheral adenocarcinomas, EGFR mutations were found 47.1% of types A, B, or C adenocarcinomas; it was less frequent (16%) in Noguchi's types D, E or F adenocarcinomas. These results suggest that type D, F adenocarcinomas are not derived from the less malignant types A-C adenocarcinomas; rather, they have arisen de novo by distinct mechanisms. Although types A and B adenocarcinomas are almost 100% cured by surgery, some type C adenocarcinoma show lymph node metastasis and relapse. EGFR mutation analysis may help identify patients who will respond to treatment with tyrosine kinase inhibitors, e.g., gefitinib.
表皮生长因子受体（EGFR）基因突变在肺癌中经常被检测到，尤其是在腺癌、女性患者和非吸烟患者中。EGFR突变与EGFR酪氨酸激酶抑制剂的临床反应密切相关。细支气管肺泡癌（BAC）表现是对该药物反应的良好预测指标。野口等人将肺的小周边腺癌分为两组。一组的特征是肿瘤细胞生长，以不同程度的纤维化取代正常肺泡细胞（A - C型），另一组表现为非取代性和破坏性生长（D - F型）。使用先前描述的13种突变的探针，我们通过TaqMan PCR检测法对手术切除的非典型腺瘤样增生（AAH）和直径达2厘米的小周边腺癌中的EGFR基因状态进行了基因分型。在95例小腺癌中，37例患者（38.9%）检测到EGFR突变，5例AAH中未发现突变。在小周边腺癌中，A、B或C型腺癌中47.1%发现EGFR突变；在野口的D、E或F型腺癌中频率较低（16%）。这些结果表明，D、F型腺癌并非源自恶性程度较低的A - C型腺癌；相反，它们是通过不同机制新生的。虽然A和B型腺癌几乎100%可通过手术治愈，但一些C型腺癌会出现淋巴结转移和复发。EGFR突变分析可能有助于识别对酪氨酸激酶抑制剂（如吉非替尼）治疗有反应的患者。
