【摘要】 目的:对照色素原位杂交法(chromogenicin situhybridization,CISH)和免疫组织化学法(immuno-histochemistry,IHC)检测乳腺癌组织中人表皮生长因子受体(human epidermal growth factor receptor-2,HER-2)基因扩增及其蛋白表达的状况。方法:采用CISH技术检测145例乳腺癌组织中HER-2的基因扩增情况,其中14例标本经过荧光原位杂交(fluorescencein situ hybridization,FISH)检测,随后分别用FISH和IHC方法检测的HER-2基因扩增及蛋白表达状况与之进行回顾性对照,并按照病理分级、淋巴结状态、绝经与否和雌激素受体(estrogen receptor,ER)/孕激素受体(progesterone receptor,PR)表达情况进行分层,分析HER-2表达与乳腺癌各高危因素之间的关系。结果:CISH检测发现,HER-2无扩增71例(50.0%),低扩增11例(7.6%),高扩增63例(43.4%)。14例FISH与CISH检测结果比较,符合率为100.0%。145例IHC与CISH检测结果的符合率为84.8%(P<0.05)。在IHC检测积分为0/+以及+++的病例中,HER-2基因扩增与蛋白表达情况基本一致,其符合率均在90%以上;而在IHC检测积分为++的标本中,HER-2基因扩增率仅为61.1%。CISH及IHC检测均显示ER/PR表达情况与HER-2阳性呈负相关,ER和PR均为阴性患者的HER-2基因扩增率和蛋白表达率明显高于ER/PR阳性的患者(CISH:68.3%vs38.8%,P<0.01;IHC:71.7%vs48.2%,P<0.01)。HER-2状态与乳腺癌病理分级、腋淋巴结转移以及绝经与否无关(P>0.05)。结论:CISH技术检测HER-2操作简便,准确性高,可以代替FISH技术,对IHC评分为++的病例应进一步确认HER-2状态。HER-2除了与ER/PR表达相关外,与其他乳腺癌高危因素无关,可作为独立指标进行检测。更多还原

【Abstract】 Objective:To detect human epidermal growth factor receptor-2(HER-2) gene amplification and protein expression by using chromosome in situ hybridization(CISH) method and compare the results with immunohistochemical assays(IHC).Methods:We assessed the amplification status of HER-2 gene with CISH method in 145 cases of breast cancer tissues.Fourteen out of 145 specimens have been tested by fluorescence in situ hybridization(FISH).HER-2 gene amplification and protein expression in the 145 cases of breast cancer tissues were tested by IHC methods.We retrospectively compared the detection results among the three methods and analyzed the correlation of HER-2 expression with various high-risk factors of breast cancer such as pathological grade,lymph node metastasis,menopausal status,and the expression of estrogen receptor(ER)/ progesterone receptor(PR).Results:Based on CISH assay,non-amplification of HER-2 gene was observed in 71 cases(50.0%),low-amplification was detected in 11 cases(7.6%),and high-amplification was assessed in 63 cases(43.4%).The concordance rate between FISH(n=14) and CISH was 100.0%(14/14).The concordance rate between IHC and CISH was 84.8%(n=145,P<0.05).In IHC 0/+ and IHC+++ cases,the HER-2 gene amplification status(>90%) was in agreement with its protein expression.However,the amplification rate of HER-2 gene was only 61.1% IHC++ cases.Both CISH and IHC detection demonstrated that expression of ER/PR was negatively related with the expression of HER-2.The amplification rate of HER-2 gene was significantly higher in ER/PR-negative patients that that in ER/PR-positive patients(CISH: 68.3% vs 38.8%,P<0.01;IHC: 71.7% vs 48.2%,P<0.01).The amplification status of HER-2 gene had no correlation with tumor pathological grade,auxiliary lymph node metastasis,and menopausal status.Conclusions:CISH for HER-2 detection is easy to handle and has high accuracy.It could replace FISH to further confirm the status of HER-2 gene in IHC++ cases.HER-2 is negatively related with ER/PR expression but has no relationship with other risk factors such as pathological grade,auxiliary lymph node metastasis,and menopausal status.HER-2 should be tested independently.更多还原