Chuang Wen-Yu, Yeh Chi-Ju, Chao Yin-Kai, Liu Yun-Hen, Chang Yu-Sun, Tseng Chen-Kan, Chang Hsien-Kun, Wan Yung-Liang, Hsueh Chuen
Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine Taoyuan, Taiwan.
Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital and Chang Gung University College of Medicine Taoyuan, Taiwan.
Int J Clin Exp Pathol. 2014 Jul 15;7(8):4847-56. eCollection 2014.
There is growing evidence that cancer-associated fibroblasts (CAFs) interact with tumor cells and play important roles in tumor progression and invasion. Podoplanin is a type-1 transmembrane glycoprotein expressed in a variety of normal human tissues, including lymphatic endothelium. Tumor cell expression of podoplanin correlates with nodal metastasis and poor prognosis in squamous cell carcinoma (SCC) of oral cavity and esophagus. Recently, podoplanin-positive CAFs have been shown to exert adverse or beneficial prognostic effect on different cancer types. However, the significance of podoplanin-positive CAFs in esophageal SCC has not been investigated. This is the first study to investigate podoplanin expression in CAFs and tumor cells by immunohistochemistry in 59 cases of surgically resected esophageal SCC. We found significant association of podoplanin expression between CAFs and tumor cells (P = 0.031). Although the abundance of podoplanin-positive CAFs per se had no prognostic effect, concordant podoplanin expression in CAFs and tumor cells (both high or both low) was strongly associated with short survival (P = 0.00088). Multivariate analysis showed that concordant podoplanin expression was the strongest independent adverse prognostic factor (hazard ratio: 3.62; 95% confidence interval: 1.69-7.77; P = 0.00094). Our data suggest that interaction between podoplanin-positive CAFs and tumor cells is important in tumor biology of esophageal SCC.
越来越多的证据表明，癌症相关成纤维细胞（CAFs）与肿瘤细胞相互作用，并在肿瘤进展和侵袭中发挥重要作用。血小板反应蛋白-1是一种在包括淋巴管内皮在内的多种正常人体组织中表达的1型跨膜糖蛋白。在口腔和食管鳞状细胞癌（SCC）中，肿瘤细胞血小板反应蛋白-1的表达与淋巴结转移及预后不良相关。最近，血小板反应蛋白-1阳性的CAFs已被证明对不同癌症类型具有不良或有益的预后影响。然而，血小板反应蛋白-1阳性的CAFs在食管SCC中的意义尚未得到研究。这是第一项通过免疫组织化学研究59例手术切除的食管SCC中CAFs和肿瘤细胞中血小板反应蛋白-1表达的研究。我们发现CAFs和肿瘤细胞之间血小板反应蛋白-1表达存在显著关联（P = 0.031）。虽然血小板反应蛋白-1阳性CAFs的丰度本身没有预后影响，但CAFs和肿瘤细胞中血小板反应蛋白-1的一致表达（均高或均低）与短生存期密切相关（P = 0.00088）。多变量分析表明，血小板反应蛋白-1的一致表达是最强的独立不良预后因素（风险比：3.62；95%置信区间：1.69 - 7.77；P = 0.00094）。我们的数据表明，血小板反应蛋白-1阳性的CAFs与肿瘤细胞之间的相互作用在食管SCC的肿瘤生物学中很重要。
