荧光原位杂交和免疫组织化学法检测乳腺浸润性导管癌中HER-2基因状态的研究

目的 比较荧光原位杂交（FISH）和免疫组织化学（IHC）两种方法检测乳腺浸润性导管癌人类表皮生长因子受体2（HER-2）基因扩增及与C-erbB-2蛋白表达结果的一致性。方法 分别采用FISH和IHC法检测346例乳腺浸润性导管癌组织HER-2基因扩增和C-erbB-2蛋白表达，并对两种方法的结果进行统计学分析。结果 346例乳腺浸润性导管癌中，FISH检测HER-2基因扩增145例（41.9％），无扩增201例（58.1％）。IHC检测显示，C-erbB-2蛋白（-）7例，（+）30例，（++）227例，（+++）82例。按乳腺癌HER-2检测指南，（-）和（+）为阴性结果，（+++）为阳性结果，（++）为不确定病例。全组IHC检测C-erbB-2蛋白阳性表达率为23.7％（82／346）。IHC检测C-erbB-2蛋白（-）的7例患者经FISH检测无HER-2基因扩增，一致率为100.0％。IHC检测C-erbB-2蛋白（+）的30例经FISH检测25例无基因扩增，一致率为83.3％；227例（++）中有65例基因扩增，一致率为28.6％；82例（+++）中有基因扩增75例，一致率为91.5％。IHC和FISH检测HER-2状态的一致率为89.9％，具有高度一致性（Kappa值=0.768，P＜0.001）。HER-2基因扩增与年龄、肿瘤大小、组织学分级及淋巴结转移均无关（P＞0.05）。结论IHC和FISH法检测乳腺浸润性导管癌HER-2表达状态有高度一致性。IHC可以作为初步筛查乳腺浸润性导管癌HER-2基因状态的首选检测方法，对于IHC检测结果为（++）的标本建议采用FISH法进一步明确HER-2基因扩增状态。

Comparison of fluorescence in situ hybridization with immunohistochemistry in detecting HER-2 status in infiltrating ductal breast carcinoma

Objective To compare the consistence of fluorescence in situ hybridization (FISH) with immunohistochemistry (IHC) in detecting human epidermalgrowth factor receptor-2 (HER-2) status in infiltrating ductal breast carcinoma.Methods The expression of C-erbB-2 protein and HER-2 gene amplification of 346 cases with infiltrating ductal breast carcinoma was tested by IHC and FISH methods,and the results were compared.Results Among 346 specimens of infiltrating ductal breast carcinoma,HER-2 gene amplification was present in 145 cases (41.9％) by FISH,and absent in 201 cases (58.1％).IHC detection of C-erbB-2 protein results showed that (-) in 7 cases,(+) in 30 cases,(++) in 227 cases and (+++) in 82 cases.According to the guidline for the detection of HER-2 in breast cancer,(-) and (+) were negative results,(+++) was positive results,and (++) was uncertain.The positive rate of C-erbB-2 protein in 346 specimens was 23.7％ (82/346).There were 7 cases with negative expression of C-erbB-2 by IHC,among which HER-2 gene amplification was absent in 7 cases with the coincidence rate of 100.0％.Five among 30 showed a negative result of (+) by IHC,but was positive in FISH,and the coincidence rate was 83.3％.In the 227 cases with a positive result of (++) by IHC,the amplification of HER-2 gene was present in 65 cases,with the coincidence rate of 28.6％.The positive result of (+ ++) was demonstrate in 82 cases,among whom the HER-2 gene amplification was detected in 75 cases,with the coincidence rate of 91.5％.The consistency of these two methods was very good in the cases with negative (-/+) or positive (+++) expression of C-erbB-2.The total concordance rate of HER-2 between IHC and FISH trials was 89.9％ with the Kappa value of 0.768(P＜0.001).HER-2 gene amplification was not related to age,tumor size,histological grade and lymph node metastasis (P＞0.05).Conclusion HER-2 expression of infiltrating ductal breast carcinoma detected by IHC was highly consistent with FISH detection.IHC is a preliminary method to detect HER-2 status in infiltrating ductal breast carcinoma.However,in the cases with positive (++) expression of C-erbB-2,FISH should be performed to detect the gene amplification of HER-2.