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

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

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-erb B-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-erb B-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-erb B-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-erb B-2蛋白阳性表达率为23.7%(82/346)。IHC检测C-erb B-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-erb B-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。

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-erb B-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-2gene amplification was present in 145 cases（ 41. 9%） by FISH,and absent in 201 cases（ 58. 1%）. IHC detection of C-erb B-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-erb B-2 protein in 346 specimens was 23. 7%（ 82/346）. There were 7 cases with negative expression of C-erb B-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-erb B-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 Cerb B-2,FISH should be performed to detect the gene amplification of HER-2.