Caveolin-1在乳腺癌间质中的表达及与预后的关系

Expression of caveolin-1 in cancer-associated fibroblasts as a prognostic indicator in breast cancer

关键词:  Caveolin-1  乳腺癌  肿瘤间质  预后

Key words:  Caveolin-1  breast cancer  cancer-associated fibroblast  prognostic outcome

摘要:

目的　检测Cav-1在乳腺癌间质中的表达，探讨其与临床病理学指标，乳腺癌分子亚型及与三阴型乳腺癌预后的关系。方法　选取258例有完整随访资料的乳腺癌切除标本，用免疫组织化学方法检测间质中CAF细胞的Cav-1表达，与肿瘤临床T分期、病理分级、淋巴结转移情况及肿瘤细胞分子标记物（ER、PR、HER-2、P53、PCNA）的表达情况进行相关性分析，同时分析在Luminal A型、Luminal B型、HER-2型和三阴型中Cav-1的差异性表达，并在三阴型乳腺癌中根据Cav-1的表达进行生存分析。结果　258例乳腺病例中，78例间质Cav-1的阴性/微弱阳性表达，94例中等阳性表达，86例强阳性表达。肿瘤分期越高，Cav-1的表达的阳性率越低，T1、T2及T3~T4各组之间差异有显著性意义（P＜0.05）。有淋巴结转移的肿瘤比无淋巴结转移的肿瘤Cav-1表达水平低，二者具有显著性差异（P＜0.05）。与患者年龄、肿瘤大小、ER、PR和HER-2的状态无关。三阴型乳腺癌与Luminal A型、B型、HER-2型相比， Cav-1的表达明显降低（P＜0.05），而A型、B型、HER-2型之间无明显差异。三阴型乳腺癌间质中Cav-1（-）、Cav-1（+）、Cav-1（++）三组生存率差异有显著性（P＜0.05），Cav-1的表达缺失是三阴型乳腺癌预后差的独立预后指标（HR=1.583 95%CI=1.031-2.431，P＜0.05）。结论　Cav-1表达水平随着临床分期的增高而降低；间质中Cav-1是三阴型乳腺癌的独立预后指标，Cav-1的低表达与预后差密切相关。

Abstract:

Objective To investigate the stromal caveolin-1(Cav-1) expression and its association with clinicalpathologic parameters, molecular subtypes of breast cancer and its prognostic significance. Methods Cav-1 expression was detected in the stroma of 258 breast cancer patients with at least 10 years of follow-up in IHC. Three groups were divided according to the staining strength (weak- , moderate+ and strong ++). Differential expression was analyzed in the light of clinical stage, pathology grade, lymphatic metastasis and the expression of molecular markers (ER,PR,HER-2,P53 and PCNA). Further analysis was performed in Luminal A, Luminal B, HER-2 and triple negative subtypes of breast cancer. Results Overexpression of stromal Cav-1 in breast cancer was associated with early stage(P=0.014) and no lymph node metastasis(P=0.011).The expression had no relationship with histological grade，ER status，PR status，HER-2 status, p53 status and PCNA status. Stromal Cav-1 expression in TN breast cancer was significantly lower than that in Luminal A, Luminal B, HER-2 molecular subtypes (P=0.014,0.035 and 0.047 respictively). Furthermore, stromal expression of Cav-1 was significantly correlated with the progression-free survival(P=0.033) and overall survival rate(P=0.031). Conclusion The absence or reduction of Cav-1 expression in stromal CAFs of invasive breast cancer would predict the poor prognostic outcome. Stromal Cav-1 expression would become a prognostic indicator.