Prognostic and histologic significances of the expression profile of membrane tissue factor for aggressive endometrial carcinomas

BACKGROUND: Tissue factor (TF) is involved in tumor-induced coagulation cascade, which plays crucial roles in the tumor microenvironment, and is being clinically explored as a therapeutic target. However, the prognostic role of TF and the related proteins in endometrial cancer is yet to be clarified and was systematically investigated in this study. MATERIALS AND METHODS: The expression profiles of membrane/cytoplasmic TF, nuclear/cytoplasmic phospho-TF (p-TF), PAR-1, PAR-2, VEGF as well as CD8, a marker for cytotoxic T cells, in tumors from 229 patients with endometrial carcinoma were immunohistochemically evaluated and correlated with clinicopathologic parameters and patient survival. Bioinformatics analyses were further conducted to strengthen the observations. RESULTS: High membrane TF (mTF) expression correlated with worse overall survival (OS), and was found to be an independent prognostic factor for unfavorable OS by the univariate and multivariate analyses (P = .028 and .0087). High mTF expression correlated with aggressive histology, and remained independent for unfavorable OS even in the aggressive histological subset (P = .037 and .0064). Moreover, mTF expression inversely correlated with CD8+ tumor-infiltrating immune cell count, and TF expression positively correlated with the infiltration of Treg cells, known to suppress CD8+ T cells, by the The Cancer Genome Atlas (TCGA) data analysis (P = .037 and .0015), suggesting that the detrimental prognostic role of mTF involves immune evasion. CONCLUSIONS: Taken together, mTF serves as a potential biomarker for patient prognosis and therapeutic target for the aggressive histological type of tumor, providing significant rationales for incorporating TF-directed drugs into the novel strategy for refractory endometrial carcinomas.