Caveolin-1在乳腺浸润性导管癌间质内癌相关成纤维细胞中的表达水平与乳腺癌分子亚型的相关性

Caveolin-1 expression in cancer-associated fibroblasts and its correlation with molecular typing of invasive ductal breast carcinoma

目的检测Caveolin-1(Cav-1)在乳腺浸润性导管癌间质内癌相关成纤维细胞(CAFs)中的表达,分析Cav-1与乳腺癌分子亚型、HER-2基因状态的相关性及其与预后的关系。方法应用免疫组织化学法检测168例乳腺癌组织Cav-1在CAFs中的表达情况。用荧光原位杂交(FISH)方法检测乳腺癌组织中HER-2基因的扩增状态。结果 Cav-1在HER-2过表达型和Luminal B型的阳性表达率均为83.3%,显著高于Luminal A型(58.1%)和Basal-like型(35.3%),差异有统计学意义(P<0.05)。乳腺癌HER-2基因扩增占39.3%(66/168),与HER-2蛋白表达呈正相关(r=0.625,P<0.05)。HER-2基因扩增组的Cav-1阳性表达率为83.3%,显著高于未扩增组的55.9%(P<0.05)。Cav-1表达水平与HER-2蛋白(r=0.253)及基因(r=0.305)表达均呈正相关(P<0.05),与预后亦明显相关(P=0.041)。结论乳腺癌间质内Cav-1表达与分子分型相关,HER-2蛋白表达水平增高及基因扩增与间质Cav-1表达水平增高呈正相关(P<0.05),乳腺癌间质CAFs中Cav-1高表达提示患者预后较好。

Objective To investigate the expression of caveolin-1 （ Cav-1 ） in breast cancer-associated fibroblasts（CAFs） and to indicate its correlation with molecular typing and gene copy number of HER-2/neu in invasive ductal breast carcinoma （IDC）. Methods One hundred and forty-five cases of breast cancer molecular subtypes were enrolled in the study. En Vision immunohistochemical method was used to detect Cav-1 expression of 168 cases with breast cancer in CAFs situation. Fluorescence in situ hybridiza- tion（FISH） was used to detect HER-2 gene amplification status of breast cancer. HER-2 gene amplification in breast cancer and the correlation with stromal expression of Cav-1 was analyzed. Results Car-1 expression in CAFs in breast cancer with pathological close- ly related to molecular typing. The positive rates in HER-2 ＋ type and Luminal B type groups were 83.3 % （35/42）, 83.3% （20/24）, significantly higher than that in Luminal A group（58. 1% ） and Basal-1 ike type group （35.3 % ）, the differences were statistically sig- nificant（ P 〈 0. 05 ）. Cav-1 expression in CAFs was positively correlated with HER-2 protein expression and HER-2 gene status. HER- 2 gene status were detected by FISH, stromal Car-1 positive rate of HER-2 gene amplification group was 83.3% （55/66） , higher than those without amplification group 55. 9% （57/102）, the differences were statistically significant （P 〈 0. 05 ）. Cav-1 expression in CAFs was positively correlated with molecular typing, HER-2 protein expression and HER-2 gene status. Stromal caveolin-1 expression was significantly associated with prognosis （P = 0. 041 ）. Conclusion Cav-1 expression in CAFs is positively correlated with molecular typ- ing, HER-2 protein expression and HER-2 gene status. The over expression of Cav-1 in stromal CAFs of invasive breast cancer predicts good prognostic outcome.