结直肠癌EGFR和HER2蛋白表达及其基因拷贝数分析

目的探索结直肠癌EGFR和HER2蛋白表达和基因拷贝数增加的频率,以及蛋白表达与基因拷贝数增加之间的相关性。方法以石蜡包埋组织芯片为材料,分别采用免疫组织化学（EGFR pharmDx^TM和HercepTest^TM试剂盒）和荧光原位杂交（FISH,LSI EGFR SpectrumOrange／CEP7 SpectrumGreen探针组合和Path V ysion^TM试剂盒）方法,检测42例中国人结直肠癌EGFR和HER2蛋白表达和基因状态。结果EGFR免疫组织化学0者18例、1＋者10例、2＋者5例、3＋者9例;HER2免疫组织化学0者39例、1＋者1例、2＋者1例、3＋者1例。通过FISH分析,EGFR基因拷贝数无明显增高18例（42．9％）,其中包括二体性14例（33．3％）、低三体性4例（9．5％）;EGFR基因拷贝数相对增高者24例（57．1％）,包括高三体性3例（7．1％）、低多体性9例（21．4％）、高多体性12例（28．6％）;本组患者中无EGFR基因扩增者。HER2基因拷贝数增加者共4例（9．5％）,其中包括基因扩增1例（2．4％）。EGFR的蛋白表达与基因拷贝数增加无相关性,两指标与肿瘤分化之间也无相关性。HER2免疫组织化学3＋和基因扩增结果一致,与乳腺癌相似。结论这组患者中,具有较高的EGFR蛋白表达和基因拷贝数增加的比率,但蛋白表达与基因状态之间以及二者与肿瘤分化程度之间都没有相关性;HER2表达和基因拷贝数增加的频率较低。

Protein overexpression and gene copy number of EGFR and HER2 in colorectal carcinoma

OBJECTIVE: To investigate the protein expression and gene copy number of EGFR and HER2, and the correlation between the two markers in colorectal carcinomas in Chinese. METHOD: Total 42 samples of paraffin-embedded colorectal carcinomas in tissue microarray format were studied by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for EGFR and HER2 protein expression and gene copy number status, respectively. RESULTS: Among 42 cases evaluated, EGFR scores were 0 in 18 cases, 1+ in 10 cases, 2+ in 5 cases and 3+ in 9 cases. HER2 expression was negative in 39 tumors, 1+ in 1 tumor, 2+ in 1 tumor and 3+ in 1 tumor. For FISH assessing EGFR, 18 (42.9%) cases showed no apparent copy number changes, including 14 (33.3%) cases of disomy and 4 (9.5%) cases of low trisomy, 24 (57.1%) cases showed increased gene copy numbers including high trisomy in 3/42 (7.1%), low polysomy in 9/42 (21.4%) and high polysomy in 12/42 (28.6%) cases. Gene amplification of EGFR is not detected. Four of 42 patients (9.5%) had increased HER2 gene copy number, including 3 patients with high polysomy and 1 patient with gene amplification. Significant association was not seen between EGFR protein expression and the gene copy number, nor between two markers and tumor differentiation. There was a highly significant concordance between the gene amplification and IHC 3+ for HER2 similar to that of breast cancer. CONCLUSIONS: Protein expression and/or increased gene copy number of EGFR is common in colorectal carcinomas but unrelated to pathological features in this cohort. HER2 protein overexpression and/or gene amplification are rare.