Epidermal growth factor receptor gene mutation defines distinct subsets among small adenocarcinomas of the lung
Epidermal growth factor receptor gene mutation defines distinct subsets among small adenocarcinomas of the lung
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DOI：
10.1016/j.lungcan.2005.12.005
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发表时间：
2006-04-01
期刊：
影响因子：
5.3
通讯作者：
Fujii, Y
中科院分区：
文献类型：
--
作者：
Haneda, H;Sasaki, H;Fujii, Y
表皮生长因子受体 (EGFR) 基因突变在肺癌（尤其是腺癌）、女性和非吸烟患者中经常检测到。 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) 的出现是对该药物反应的良好预测指标。野口等人。将肺周围小腺癌细分为两组。一组的特点是肿瘤细胞生长取代了具有不同程度纤维化的正常肺泡细胞（A-C型），另一组则表现出非替代性和破坏性生长（D-F型）。使用先前描述的 13 种突变探针，我们使用 TaqMan PCR 测定对手术切除的非典型腺瘤性增生 (AAH) 和直径达 2 cm 的小周围腺癌中的 EGFR 基因状态进行了基因分型。在95例小型腺癌中，37例（38.9%）检测到EGFR突变，5例AAH未发现突变。在小周围型腺癌中，EGFR 突变占 A、B 或 C 型腺癌的 47.1%；在野口的 D、E 或 F 型腺癌中，这种情况的发生率较低（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，它们是通过不同的机制从头出现的。虽然A型和B型腺癌几乎可以100%通过手术治愈，但部分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（例如吉非替尼）治疗有反应的患者。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
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 at. 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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.