乳腺癌中Tenascin C、α-SMA和PDGFRα的表达及意义

Expression of Tenascin C, α-SMA, PDGFRα in breast cancer and their significance

目的探讨乳腺癌组织间质成纤维细胞活化相关分子标记Tenascin C(TN-C)、α-SMA和PDGFRα的表达,明确其与乳腺浸润性导管癌临床病理特征的关系。方法采用免疫组化SP法检测81例乳腺浸润性导管癌间质及癌细胞中TN-C、α-SMA和PDGFRα蛋白表达水平,分析这三者与乳腺癌临床病理特征的关系。结果在乳腺腺病、乳腺导管内癌和浸润性导管癌三种不同病变中,TN-C在间质成纤维细胞中的阳性率分别为0、0、51.9%(P<0.001);α-SMA的阳性率分别为0、20.0%、70.4%(P<0.001);PDGFRα的阳性率分别为10.0%、0、37.0%(P<0.01)。三者在间质表达均与乳腺癌分子亚型相关(P<0.05),且均在HER-2阳性乳腺癌间质中的表达水平最高。TN-C、α-SMA和PDGFRα在乳腺癌细胞中的表达水平明显低于导管内癌或乳腺腺病,其中TN-C在癌细胞中表达水平与患者年龄有关(P<0.05),乳腺癌细胞α-SMA表达水平与淋巴结转移显著相关(P<0.05),但PDGFRα在癌细胞中表达水平与患者年龄、肿瘤组织学分级、肿瘤分期、淋巴结转移、分子分型均无明显相关性(P>0.05)。结论与乳腺腺病和乳腺导管内癌相比,乳腺浸润性导管癌间质成纤维细胞中TN-C、α-SMA和PDGFRα的表达水平明显增高,并与乳腺癌分子分型存在明显相关性。提示间质成纤维细胞活化是促进乳腺癌恶性演进的重要因素,成纤维细胞活化相关分子有望成为乳腺癌临床预后的分子标记。

Purpose To investigate the expression of molecular markers related to fibroblast activation in the stroma of breast cancer, and to determine the correlation with the clinicopathological features of breast invasive ductal carcinoma. Method The expression of Tenascin-C (TN-C),α-SMA and PDGFRα in 81 cases of breast cancer was detected by immunohistochemistry, and the relationship was analysed between these molecules and the clinicopathological features of breast cancer. Results Among the breast adenosis, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), the expression of TN-C in the stromal fibroblasts was detected as 0, 0, and 51.9%, respectively ( P <0.001). The positive rates of α-SMA in stroma was 0, 20.0%, 70.4%( P <0.001) and those of PDGFRα in three types of breast lesions was 10.0%, 0, 37.0%( P <0.01), respectively. The expression of these proteins in the stroma was closely correlated with different molecular subtype of IDC ( P <0.05), and higher positive level of these proteins was detected in the stroma of HER-2 + breast carcinoma compared with luminal and triple negative breast cancer. In contrast, the expression of TN-C,α-SMA and PDGFRα in the epithelial compartments of IDC was significantly lower than those in DCIS or breast adenosis. In addition, the expression of TN-C in the epithelium of breast cancer was related to the patient’s age ( P <0.05), and high expression of α-SMA in epithelial compartment was correlated with lymph node involvement of breast cancer ( P < 0.05). However, the expression of PDGFRα in the breast cancer epithelial cells showed no significant correlation with patient’s age, histological grade, tumor stage, lymph node metastasis and molecular subtypes ( P >0.05). Conclusion In summary, compared with breast adenosis and DCIS, high expression of TN-C,α-SMA and PDGFRα is detected in the stroma of IDC and closely associated with the development of HER-2 + breast cancer, indicating that activation of stromal fibroblasts may provide the permissive niche that cooperates with activation of oncogene in tumor cells to promote progression of breast carcinoma and to result in worse clinical outcome.