食管癌食管胃交界处癌和胃癌组织中表皮生长因子受体基因突变的检测及意义

摘要

Objective Tyrosine kinase inhibitors ( TKIs) of the epidermal growth factor receptor ( EGFR) have been reported to be effective in the treatment of esophageal and esophagogastric junction cancers.The aim of this study was to detect the frequency of EGFR mutation and expression in Chinese patients with esophageal , esophagogastric junction and gastric cancers , and to clarify the value of EGFR mutation and expression in predicting the efficacy of TKI in the treatment of these tumors .Methods In this study, 180 tumor samples with histologically confirmed esophageal cancer (39 cases), cancer of the esophagogastric junction ( 92 cases ) and gastric cancer ( 49 cases ) were collected .Twenty-nine different EGFR mutations in exons 18-21 were assessed by real-time PCR-optimized oligonucleotide probe method. EGFR protein expression was evaluated by immunohistochemistry ( IHC) in 89 tumor samples.Results The mutation analysis for EGFR ( exons 18-21) showed no mutations in any of the hotspots of the gene in the 180 tumor samples analyzed .EGFR expression was negative in 12 tumor samples, 1+in 31 tumor samples, 2+in 24 tumor samples,and 3+in 22 tumor samples.EGFR expression was 2+or 3+in 12 (92.3%)of the 13 esophageal squamous cell carcinomas , 29 (47.5%) of the 61 esophagogastric junction cancers , and 5 (33.3%) of the 15 gastric adenocarcinomas .Conclusions Our results indicate that EGFR mutation in exons 18-21 is absent in the examined samples of esophageal , esophagogastric junction and gastric cancers . More studies are warranted to explore the predictive biological markers for the therapeutic response to EGFR TKI.%目的：探讨表皮生长因子受体（ EGFR ）基因突变和表达对小分子酪氨酸激酶抑制剂（TKI）治疗食管癌、食管胃交界处（EGJ）癌和胃癌疗效预测的价值。方法收集经甲醛固定的食管癌、EGJ癌和胃癌石蜡包埋组织标本180例，其中食管癌39例，EGJ癌92例，胃癌49例。采用荧光PCR-优化寡核苷酸探针法检测EGFR基因第18～21外显子的29种突变情况，免疫组化法检测89例肿瘤组织中的EGFR蛋白表达。结果180例肿瘤组织中均未检测到EGFR 18～21号外显子突变。89例肿瘤组织中，EGFR（-）12例，EGFR（＋）31例，EGFR（＋＋）24例，EGFR（＋＋＋）22例。13例食管鳞癌组织中，EGFR （＋＋）或EGFR（＋＋＋）12例（92．3％）。61例EGJ癌组织中，EGFR （＋＋）或EGFR （＋＋＋）29例（47．5％）。15例胃腺癌组织中，EGFR（＋＋）或EGFR（＋＋＋）5例（33．3％）。结论180例食管癌、EGJ癌和胃癌组织中无EGFR基因18～21号外显子突变，应进行更多的研究来探索可以预测小分子TKI类药物治疗食管癌、EGJ癌和胃癌疗效的分子标志物。