悪性子宮内膜癌における膜組織因子の発現プロファイルの予後および組織学的意義

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.

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.

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 = 0.028 and 0.0087). High mTF expression correlated with aggressive histology, and remained independent for unfavorable OS even in the aggressive histological subset (p = 0.037 and 0.0064). 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 TCGA data analysis (p = 0.037 and 0.0015), suggesting that the detrimental prognostic role of mTF involves immune evasion.

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.