乳腺浸润性癌组织人表皮生长因子受体-2基因扩增状态与蛋白表达的比较及其与临床病理特征的相关性

Comparison of human epidermal growth factor receptor-2 gene amplification status and protein expression in invasive breast carcinoma and its correlation with clinicopathological characteristics

目的探讨乳腺癌组织中人表皮生长因子受体-2(HER2)蛋白表达和基因扩增的一致性及临床意义,并分析HER2基因扩增与临床病理特征的相关性。方法采用全自动免疫组化(IHC)及荧光原位杂交(FISH)的方法,分别检测101例乳腺浸润性癌患者的蛋白表达及基因扩增状态。分析2种不同检测方法结果的差异,并揭示其临床意义。结果 101例浸润性乳腺癌中, IHC显示HER2蛋白1例为(-), 6例为(+), 81例为(++), 13例为(+++)。FISH显示HER2基因无扩增为75例, HER2基因有不同程度的扩增为26例。HER2蛋白(-)的1例及(+)的6例HER2基因均无扩增, HER2蛋白(++)的81例中HER2基因扩增的有14例, HER2蛋白(+++)的13例中HER2基因扩增的有12例。101例中FISH检测共发现9例17号染色体多体。FISH和IHC 2种检测方法的差异有统计学意义(P<0.05)。FISH结果与患者的年龄相关(P<0.05),与肿瘤组织学分级、肿瘤最大径、Ki67表达及患者腋窝淋巴结转移情况均无相关性(P>0.05)。结论 IHC与FISH具有较高的一致性, IHC染色强度和基因扩增状态成正相关, IHC可作为临床使用赫赛汀的初筛方法,应联合应用FISH检测来确定临床用药及判断患者预后情况。

Objective To investigate the consistency and clinical significance of human epidermal growth factor receptor-2(HER2) protein expression and gene amplification in breast cancer tissue, and to analyze the correlation between HER2 gene amplification and clinicopathological characteristics. Methods Immunohistochemistry(IHC) and fluorescence in situ hybridization(FISH) were used to detect the protein expression and gene amplification in 101 patients with invasive breast carcinoma. The difference of the results of two different detection methods were analyzed and clinical significance was analyzed. Results In 101 cases of invasive breast cancer, IHC showed HER2 protein was negative in 1 case, positive in 6 cases, double-positive in 81 cases, and triple-positive in 13 cases. FISH showed that there were 75 cases of HER2 gene without amplification, and 26 cases of HER2 gene with different degrees of amplification. No HER2 gene amplification was observed in 1 case of HER2 protein(-) and 6 cases of HER2 protein(+), HER2 gene amplification was observed in 14 of 81 cases of HER2 protein (■) and in 12 of 13 cases of HER2 protein (■) . In 101 cases,9 cases of chromosome 17 polysomes were found by FISH. The difference between FISH and IHC was statistically significant (P < 0. 05). FISH results were correlated with age of patients (P < 0. 05),and there was no correlation between FISH results and tumor histological grade,tumor maximum diameter,Ki67 expression and axillary lymph node metastasis (P > 0. 05). Conclusion IHC has high consistency with FISH. IHC staining intensity is positively correlated with gene amplification status. IHC method can be used as the primary screening method for clinical use of Trastuzumab,and FISH test should be used together to determine clinical medication and judge the prognosis of patients.