显色原位杂交和免疫组织化学检测乳腺癌HER2/neu基因状况和蛋白表达的对照性研究

Comparision of HER2/neu oncogene detected by chromogenic in-situ hybridization and immunohistochemistry in breast cancer

目的探讨显色原位杂交(CISH)在检测乳腺癌中 HER2/neu 基因扩增上的作用。方法挑选乳腺浸润性导管癌患者组织石蜡蜡块(回顾性255例,前瞻性271例),进行免疫组织化学(IHC)、CISH 检测。15例回顾性标本送往德国 HERA 检测中心进行 FISH 检测。结果 (1)回顾性病例中 IHC 阳性3+者 CISH 基因扩增率为91.6%(120/131),IHC 2+者 CISH 基因扩增率为56.5%(39/69),IHC 与 CISH 检测结果符合率为81.2%(207/255),两者明显相关(P<0.01)。(2)前瞻性病例中 IHC 蛋白过表达率31.7%,CISH 基因扩增率27.3%。IHC 3+者 CISH 基因扩增率为91.4%(53/58),IHC 2+者 CISH 基因扩增率为46.4%(13/28),IHC 与 CISH 检测结果符合率为89.7%(243/271),两者明显相关(P<0.01)。(3)经德国检测中心荧光原位杂交(FISH)检测的15例中14例和 CISH 结果完全一致,1例检测失败,而 CISH 为无扩增。(4)CISH 检测基因扩增与雌激素受体(ER)、孕激素受体(PR)表达明显负相关(P 值均<0.01)。结论 CISH 检测 HER2基因扩增结果与IHC 检测蛋白过表达及 FISH 结果高度一致,CISH 是检测 HER2基因扩增的一项新技术。

Objective Through comparision of HER2/neu oncogene detected by chromogenic in situ hybridization （CISH） and immunohistoehemistry （IHC） in breast cancer, to explore the effect of CISH on detecting gene amplification of HER2. Methods Selected formalin-fixed paraffin-embedded breast samples whose pathological types were infiltrating duetal carcinomas （255 retrospective samples, 271 prospective samples ） , and these samples were detected by IHC and CISH. Results （1） In the retrospective study, CISH identified gene amplification in 91.6% of IHC score 3 ＋ tumors （ 120/131 ） and in 56. 5% of IHC score 2 ＋ tumors（39/69）, thus the concordant ratio between IHC and CISH was 81.2% （207/255）. The two results showed significant correlation （P 〈 0. 01 ）. （2） In the prospective study, the ratio of HER2 protein over expression detected by IHC was 31.7% , the ratio of HER2 gene amplification detected by CISH was 27. 3%. CISH identified gene amplification in 91.4% of IHC score 3 ＋ tumors （53/58） and in 46.4% of IHC score 2 ＋ tumors （ 13/28）, Concordant ratio between IHC and CISH was 89. 7% （243/271）. Two results showed significant correlation （ P 〈 0. 01 ）. （ 3 ） Paired CISH/FISH results were concordant in 14 of 15 cases. The remaining case was detected by FISH, but showed no HER2 gene amplification by CISH. （4）The gene amplification by CISH had a significantly reverse correlation with ER and PR expression （ P 〈 0.01 ）. Conclusions The results of HER2 gene amplification detected by CISH have high concordance with the results detectd by IHC and FISH. CISH is a novel technique for detecting HER2 gene amplification.