Department of Cardiothoracic Surgery, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
Med Oncol. 2014 Mar;31(3):803. doi: 10.1007/s12032-013-0803-5. Epub 2014 Jan 23.
Mutation in epidermal growth factor receptor (EGFR) gene may predict response to chemotherapy in non-small cell lung cancer (NSCLC). However, the correlation between EGFR gene copy status and protein levels of drug-resistant genes, such as excision repair cross-complementing 1 (ERCC1) and breast cancer 1 (BRCA1), remains unclear. We retrospectively analyzed formalin-fixed, paraffin-embedded tumor tissues from 109 Chinese patients with NSCLC. EGFR gene copy number was evaluated by fluorescence in situ hybridization (FISH), and protein levels of platinum-resistance-associated genes, including ERCC1 and BRCA1, were determined by immunohistochemical staining. High EGFR gene copy (EGFR FISH-positive) was found in 21.1% of the patients (amplification in 7.3% and high polysomy in 13.8%, respectively). Immunohistochemical analysis revealed that ERCC1 protein expression was not associated with clinicopathological factors, whereas a significantly higher BRCA1 positive rate was found in poorly differentiated tumors (P=0.02). Further association studies demonstrated that EGFR gene copy number status was not correlated with protein levels of ERCC1 or BRCA1; however, expression of ERCC1 was significantly associated with that of BRCA1 in this set of Chinese patients with NSCLC (P<0.001, r=0.484). Our study demonstrated that EGFR gene copy number status was not correlated with ERCC1 or BRCA1 protein expression, but ERCC1 protein levels were significantly correlated to BRCA1 protein expression levels in tumor tissues from Chinese patients with NSCLC.
表皮生长因子受体(EGFR)基因突变可能预测非小细胞肺癌(NSCLC)对化疗的反应。然而,EGFR 基因拷贝状态与耐药基因(如切除修复交叉互补基因 1(ERCC1)和乳腺癌基因 1(BRCA1))的蛋白水平之间的相关性尚不清楚。我们回顾性分析了 109 例中国 NSCLC 患者的福尔马林固定、石蜡包埋肿瘤组织。通过荧光原位杂交(FISH)评估 EGFR 基因拷贝数,通过免疫组织化学染色测定铂耐药相关基因(包括 ERCC1 和 BRCA1)的蛋白水平。21.1%的患者存在 EGFR 基因高拷贝数(EGFR FISH 阳性)(扩增 7.3%,高多倍体 13.8%)。免疫组化分析显示,ERCC1 蛋白表达与临床病理因素无关,而在低分化肿瘤中 BRCA1 阳性率显著升高(P=0.02)。进一步的关联研究表明,EGFR 基因拷贝数状态与 ERCC1 或 BRCA1 蛋白水平无关;然而,在这组中国 NSCLC 患者中,ERCC1 的表达与 BRCA1 的表达显著相关(P<0.001,r=0.484)。我们的研究表明,EGFR 基因拷贝数状态与 ERCC1 或 BRCA1 蛋白表达无关,但在中国 NSCLC 患者的肿瘤组织中,ERCC1 蛋白水平与 BRCA1 蛋白表达水平显著相关。