色素原位杂交法分析乳腺癌HER-2蛋白过表达者的基因状态

HER-2 gene status detected by chromogenic in situ hybridization in breast cancer with HER-2 protein over-expression

目的采用色素原位杂交(CISH)检测乳腺癌HER-2蛋白过表达者的HER-2基因状态,探讨HER-2蛋白表达与基因扩增的一致性。方法采用Zymed公司SpoT-Light HER-2 CISTTM试剂盒,按照美国临床肿瘤学会/美国病理医师学会(ASCO/CAP)联合工作组推荐的结果判读标准,经免疫组织化学(IHC)方法确认236例HER-2蛋白表达阳性,其中IHC(++)148例,IHC(+++)88例,对上述乳腺癌石蜡标本的HER-2基因行CISH检测。结果乳腺癌HER-2蛋白高表达者总基因扩增率为70.34%,其中HER-2表达IHC(++)者基因扩增率为59.46%(88/148),IHC(+++)者基因扩增率为88.64%(78/88),两者基因扩增状态差异有统计学意义(χ2=26.35,P<0.01)。CISH检测的HER-2基因扩增情况与雌激素受体(ER)、孕激素受体(PR)表达呈明显负相关(P<0.01)。结论 CISH是一项简便经济的检测HER-2基因扩增技术,IHC(+++)与CISH阳性的一致性较高,但IHC(++)与CISH阳性的符合率略低,有必要进一步行CISH或荧光分子探针原位杂交(FISH)检测明确基因扩增状态。

Objective To identify the HER-2 gene status in breast cancer with HER-2 protein over-expression by chromogenic in situ hybridization（CISH） , and to study the correlation between HER-2 gene amplification and its protein over-expression. Methods Two hundred and thirty-six cases of breast cancer with paraffin-embedded sections with HER-2 protein over-expression detected by immunohistochemistry（IHC）, including IHC 2 ＋ 148 cases and IHC 3 ＋ 88 cases, were tested by CISH （SpoT-Light HER-2 CISTTM Zymed） for HER-2 gene status, and these results were determined by using the criterion of American Society of Clinical Oncology/College of American Pathologists guideline. Results In this study, CISH identified HER-2 gene amplification in 70. 34% breast cancer with HER-2 protein over-expression. There were 88 cases（59.46% ） and 78 cases （88.64%） respectively identified as HER- 2 gene amplification in 148 samples with IHC 2 ＋ and 88 samples with IHC 3 ＋ , which showed a significant correlation（P 〈0. 01 ）. Moreover, the gene amplification tested by CISH had a significantly negative correlation with ER and PR expression （P 〈 0. 01 ）. Conclusion CISH is a convenient and economical technique for detecting HER-2 gene status. The concordance rate is very high between IHC 3 ＋ and CISH positive result, however, the coincidence rate between IHC 2 ＋ and CISH positive result is lower. Therefore, it is essential that the samples with IHC 2 ＋ should be detected to identify HER-2 gone amplification by CISH or FISH.