非小细胞肺癌组织及胸水中EGFR基因TKD结构域突变的临床病理研究

目的检测非小细胞肺癌（NSCLC）EGFR基因酪氨酸蛋白激酶结构域（TKD）18—21外显子突变情况；比较常见突变（19号外显子的缺失突变及21号外显子错义突变-L858R）和非常见突变患者的临床病理改变。方法从91例NSCLC组织及胸水标本中提取基因组DNA；巢式PCR方法扩增EGFR基因18～21外显子；应用PCR-LIS-SSCP及直接测序方法检测EGFR基因18～21外显子突变情况；对存在常见及非常见突变患者的组织病理、酪氨酸蛋白激酶小分子抑制剂（TKIs）的治疗反应和预后等的临床病理改变进行分析。结果91例NSCLC患者中27例存在EGFR基因TKD突变，其中常见突变19例，突变率为20．9％（19／91）；非常见突变8例（其中4例为20号外显子的短片段插入突变），突变率为8．8％（8／91）。两组患者组织学类型均为腺癌，且对TKIs治疗均有较好反应。2例非常见突变患者化疗时出现肺间质纤维化（ILD）。结论NSCLC患者EGFR基因TKD存在多种非常见突变；具有非常见突变的患者可能存在独特的临床病理改变。

Common and uncommon mutations of EGFR gene TK domain in non-small cell lung carcinoma tissues and pleural fluid cytology: a clinicopathological study

Objective To investigate the mutation status of EGFR exons 18 to 21 in 91 patients with non-small cell lung carcinoma (NSCLC), and to compare the clinical and pathological changes of NSCLC patients with common (exon 19 in-frame deletions and exon 21 missense mutant L858R) and uncommon mutations (exons 18-21 of EGFR gene). Methods Genomic DNA from NSCLC tissue and pleural fluid was extracted;Nested PCR was used to amplify the exon 18-21 of EGFR gene;PCR-LIS-SSCP method and direct sequencing were used to investigate EGFR mutations in exons 18 to 21;Clinical pathological data and the reaction for tyrosine kinase inhibitors (TKIs) therapy were analyzed between two groups of the common and uncommn gene mutations of EGFR gene tyrosine kinase domain (TKD). Results EGFR mutations were detected in 27 of 91 NSCLC patients,in which 19 of 27 had common mutations with mutation rate of 20.9% (19/91);the uncommon mutations were found in 8 of 27 patients with mutation rate of 8.8% (8/91). The histopathological type of both groups patients was adenocarcinoma and all of them showed good reaction to TKIs treatment. Two groups of patients with uncommon mutations developed interstitial lung disease (ILD) during TKIs treatinent. Conclusion The NSCLC patients exist several uncommon EGFR gene mutations;Patients with uncommon mutation may show unique characteristics in the clinicopatholigical changes.