Takeo Minaguchi

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

Abstract 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.

Prevalence of venous thromboembolism at pretreatment screening and associated risk factors in 2086 patients with gynecological cancer

AbstractAimPostoperative pulmonary embolism can be a fatal surgical complication and is thought to occur secondary to asymptomatic venous thromboembolism (VTE) that exists preoperatively in some patients. The purpose of this study was to clarify the frequency and risk factors of pretreatment VTE in gynecological cancer patients.MethodsThis study investigated 2086 patients with gynecological cancer (cervix, n = 754; endometrium, n = 862; ovary, n = 470) who underwent initial treatment between 2004 and 2017. Pretreatment VTE screening was performed with D‐dimer (DD) levels in these patients. Based on this, the associated risk factors were retrospectively analyzed.ResultsPretreatment VTE was discovered in 7.3% of patients with cervical cancer, 11.5% of those with endometrial cancer and 27.0% of those with ovarian cancer. Significant independent risk factors were: age greater than or equal to 60 years and tumor long diameter greater than or equal to 40 mm for cervical cancer; age greater than or equal to 60 years, stage III/IV advanced disease, clear cell carcinoma and tumor long diameter greater than or equal to 60 mm for endometrial cancer; and age greater than or equal to 60 years, clear cell carcinoma and massive ascites for ovarian cancer.ConclusionPretreatment asymptomatic VTE is very frequent in gynecological cancer patients. It may be beneficial to consider measuring DD or performing venous ultrasonography in patients with the above risk factors.

PD-L1 and CD4 are independent prognostic factors for overall survival in endometrial carcinomas

Abstract Background Tumor microenvironment (TME) including the immune checkpoint system impacts prognosis in some types of malignancy. The aim of our study was to investigate the precise prognostic significance of the TME profile in endometrial carcinoma. Methods We performed immunohistochemistry of the TME proteins, PD-L1, PD-1, CD4, CD8, CD68, and VEGF in endometrial carcinomas from 221 patients. Results High PD-L1 in tumor cells (TCs) was associated with better OS (p = 0.004), whereas high PD-L1 in tumor-infiltrating immune cells (TICs) was associated with worse OS (p = 0.02). High PD-L1 in TICs correlated with high densities of CD8+ TICs and CD68+ TICs, as well as microsatellite instability (p = 0.00000064, 0.00078, and 0.0056), while high PD-L1 in TCs correlated with longer treatment-free interval (TFI) after primary chemotherapy in recurrent cases (p = 0.000043). High density of CD4+ TICs correlated with better OS and longer TFI (p = 0.0008 and 0.014). Univariate and multivariate analyses of prognostic factors revealed that high PD-L1 in TCs and high density of CD4+ TICs were significant and independent for favorable OS (p = 0.014 and 0.0025). Conclusion The current findings indicate that PD-L1 and CD4+ helper T cells may be reasonable targets for improving survival through manipulating chemosensitivity, providing significant implications for combining immunotherapies into the therapeutic strategy for endometrial carcinoma.