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目的:探讨乳腺癌组织中人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2/neu)基因扩增与其蛋白产物C-erbB-2表达之间的相关性,并评价应用组织芯片进行荧光原位杂交(luorescencein situ hybridization,FISH)检测HER-2/neu基因扩增的临床应用价值。方法:收集80例乳腺癌组织制备芯片,以10例乳腺良性病变周围正常乳腺组织为对照组,分别进行FISH和免疫组织化学(immunohistochemistry,IHC)检测乳腺癌组织中HER-2/neu基因扩增及C-erbB-2蛋白的表达情况。结果:80例乳腺癌组织中,FISH法检测结果显示,有18例样品存在HER-2/neu基因扩增,阳性率为22.5%(18/80);IHC法检测结果提示,C-erbB-2蛋白强阳性(+++)表达的组织中HER-2/neu基因阳性率为90.9%(10/11),中等强度阳性(++)表达的组织中阳性率为66.7%(4/6),阴性或弱阳性(0/+)表达的组织中基因扩增的阳性率仅为6.3%(4/63)。在浸润性导管癌Ⅰ级中HER-2/neu基因扩增的阳性率为10.0%(2/20),Ⅱ级中为23.3%(7/30),Ⅲ级中为30.0%(9/30)。10例正常乳腺对照组织中均未检测到HER-2/neu基因扩增及C-erbB-2蛋白的表达。统计结果显示,C-erbB-2蛋白强阳性(+++)和中等强度阳性(++)表达者HER-2/neu基因扩增的阳性率显著高于C-erbB-2蛋白阴性或弱阳性表达者,差异有统计学意义(P<0.01);HER-2/neu基因扩增的阳性率随组织学分级的提高而升高。IHC法检测C-erbB-2蛋白的表达与FISH法检测HER-2/neu基因扩增有较高的一致性(Kappa=0.746,P<0.05),但C-erbB-2蛋白的表达仍有一定比例的假阳性或假阴性。结论:乳腺癌组织HER-2/neu基因扩增与C-erbB-2蛋白的过表达密切相关并与组织学分级有关。FISH法检测HER-2/neu基因状态比C-erbB-2蛋白的表达更客观和可靠,C-erbB-2蛋白的检测可作为初筛手段。应用组织芯片进行FISH法检测结果可靠,具有实用、高效和经济的优点,对于大样本的研究具有优势。
OBJECTIVE: To investigate the correlation between the amplification of human epidermal growth factor receptor-2 (HER-2 / neu) gene and its protein C-erbB-2 in breast cancer tissues. Application of tissue microarray in fluorescence in situ hybridization (luorescencein situ hybridization, FISH) detection HER-2 / neu gene amplification of clinical value. Methods: Chips from 80 breast cancer tissues were collected and 10 normal breast tissues around benign breast lesions were selected as the control group. The amplification of HER-2 / neu gene in breast cancer tissues was detected by FISH and immunohistochemistry (IHC) And C-erbB-2 protein expression. Results: In 80 cases of breast cancer, the results of FISH showed that there were 18 cases of HER-2 / neu gene amplification, the positive rate was 22.5% (18/80); IHC test results showed that C-erbB- The positive rate of HER-2 / neu gene expression was 90.9% (10/11) in the tissues strongly positive (+++) and 66.7% (4/6 ). The positive rate of gene amplification was only 6.3% (4/63) in negative or weakly positive (0 / +) expression tissues. The positive rate of HER-2 / neu gene amplification in grade I invasive ductal carcinoma was 10.0% (2/20), in grade II 23.3% (7/30) and in grade III 30.0% (9/30 ). No HER-2 / neu gene amplification and C-erbB-2 protein expression were detected in 10 normal breast tissues. The statistical results showed that the positive rate of HER-2 / neu gene amplification in C-erbB-2 protein positive (+++) and moderate-intensity positive (++) expression was significantly higher than that of C-erbB-2 protein (P <0.01). The positive rate of HER-2 / neu gene amplification increased with the increase of histological grade. The expression of C-erbB-2 protein in IHC assay was higher than that in FISH assay (Kappa = 0.746, P <0.05), but the expression of C-erbB-2 protein was still high A certain percentage of false positives or false negatives. Conclusion: The amplification of HER-2 / neu gene in breast cancer is closely related to the overexpression of C-erbB-2 and is related to histological grade. The detection of HER-2 / neu by FISH was more objective and reliable than the expression of C-erbB-2 protein. The detection of C-erbB-2 protein could be used as a screening tool. The application of tissue microarray for FISH has the advantages of reliable, practical, efficient and economic results, and has advantages for large sample research.