Stadlmann Sylvia, Gueth Uwe, Reiser Ulrich, Diener Pierre-Andre, Zeimet Alain Gustave, Wight Edward, Mirlacher Martina, Sauter Guido, Mihatsch Michael J, Singer Gad
Institute for Pathology, University Hospital of Basel, Basel, Switzerland.
Mod Pathol. 2006 Apr;19(4):607-10. doi: 10.1038/modpathol.3800575.
Success of epidermal growth factor receptor (EGFR) targeting agents in different cancer types is related to EGFR gene mutations and/or copy number gains. We investigated the EGFR gene status and protein expression by DNA mutational analysis, fluorescence in situ hybridization (FISH), and immunohistochemistry in tumor tissues from 80 patients with primary and corresponding recurrent ovarian serous carcinomas. The patients were classified into six groups with ascending EGFR gene copy numbers. EGFR amplification and high polysomy (FISH+) was present in a significant fraction of the primary (20%) and recurrent (22%) ovarian carcinomas. On mutational analysis, only one tumor with a silent EGFR mutation was observed, and this was the only carcinoma with high-level amplification. EGFR protein immunoexpression was seen in 28% of primary and 33% of recurrent carcinomas and correlated to amplification in the primary tumors (P = 0.003). In recurrent carcinoma, moderate and strong EGFR expression was associated with amplification (P = 0.034). These molecular events potentially have impact on the responsiveness to EGFR targeting agents in ovarian cancer.
表皮生长因子受体(EGFR)靶向药物在不同癌症类型中的疗效与EGFR基因突变和/或拷贝数增加有关。我们通过DNA突变分析、荧光原位杂交(FISH)和免疫组织化学方法,对80例原发性及相应复发性卵巢浆液性癌患者的肿瘤组织进行了EGFR基因状态和蛋白表达研究。患者按EGFR基因拷贝数递增分为六组。在相当一部分原发性(20%)和复发性(22%)卵巢癌中存在EGFR扩增和高多体性(FISH+)。在突变分析中,仅观察到1例具有EGFR沉默突变的肿瘤,且这是唯一具有高水平扩增的癌。28%的原发性癌和33%的复发性癌可见EGFR蛋白免疫表达,且与原发性肿瘤中的扩增相关(P = 0.003)。在复发性癌中,EGFR中度和强表达与扩增相关(P = 0.034)。这些分子事件可能对卵巢癌中EGFR靶向药物的反应性产生影响。