Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Cancer Sci. 2011 Aug;102(8):1590-6. doi: 10.1111/j.1349-7006.2011.01985.x. Epub 2011 Jun 27.
Caveolin-1 (Cav-1) has been extensively characterized in cancer biological research. However, the role of Cav-1 in the interaction between tumor and stromal cells remains unclear. In the present study, we examined Cav-1 expression in tumor cells and stromal cells in breast cancer tissue by immunohistochemical analysis and evaluated its prognostic value in a training cohort. Immunohistochemical analysis of Cav-1 expression was scored as (++), (+) or (-) according to the proportion of positively stained tumor cells (T) and stromal cells (S). Correlation analysis between tumor/stromal Cav-1 expression and clinicopathological parameters revealed that only T(++) Cav-1 status was positively associated with tumor size and histological nodal status (P = 0.019 and 0.021, respectively). Univariate analysis revealed that combined T(++)/S(-) status was significantly correlated with unfavorable prognostic outcomes (P < 0.001). Multivariate analysis demonstrated that this combined status is an independent prognostic factor for primary breast cancer (P = 0.002). Clinical outcomes in different subgroups of breast cancer patients were also strictly dependent on this combined status (P < 0.05). The prognostic value of T(++)/S(-) Cav-1 status was also validated in the testing cohort. Collectively, our data indicate that high Cav-1 expression in tumor cells and lack of this expression in stromal cells could help identify a particular subgroup of breast cancer patients with potentially poor survival. Further studies are required to understand the regulatory mechanism of Cav-1 in the tumor microenvironment.
窖蛋白-1(Cav-1)在癌症生物学研究中得到了广泛的研究。然而,Cav-1 在肿瘤细胞与基质细胞相互作用中的作用仍不清楚。在本研究中,我们通过免疫组织化学分析检测了乳腺癌组织中肿瘤细胞和基质细胞中的 Cav-1 表达,并在训练队列中评估了其预后价值。根据阳性染色的肿瘤细胞(T)和基质细胞(S)的比例,将 Cav-1 表达的免疫组织化学分析评分(++)、(+)或(-)。肿瘤/基质 Cav-1 表达与临床病理参数之间的相关性分析表明,只有 T(++)Cav-1 状态与肿瘤大小和组织学淋巴结状态呈正相关(P = 0.019 和 0.021)。单因素分析显示,T(++)/S(-)联合状态与不良预后结果显著相关(P < 0.001)。多因素分析表明,这种联合状态是原发性乳腺癌的独立预后因素(P = 0.002)。不同乳腺癌患者亚组的临床结局也严格依赖于这种联合状态(P < 0.05)。T(++)/S(-)Cav-1 状态的预后价值也在检验队列中得到验证。综上所述,我们的数据表明,肿瘤细胞中 Cav-1 的高表达和基质细胞中缺乏这种表达可能有助于识别具有潜在不良生存的特定乳腺癌患者亚组。需要进一步研究以了解 Cav-1 在肿瘤微环境中的调控机制。