Tumor-infiltrating lymphocytes (TILs) have been reported as a prognostic factor in various cancers and are a promising target for immunotherapy. To investigate whether TILs have any impact on the prognosis of angiosarcoma patients, 55 non-treated patients (40 patients at stage 1 with cutaneous localized tumors, 4 patients at stage 2 with lymph node metastases and 11 patients at stage 3 with distant metastases) with angiosarcoma were evaluated retrospectively by immunohistochemistry stained CD4, CD8, FOXP3 and Ki67. The Kaplan-Meier method was used to estimate overall survival with patients at stage 1. Survival differences were analyzed by the log-rank test. Patients with higher numbers of CD8 1 TILs in their primary tumors survived significantly longer compared with patients with lower values. Moreover, the number of CD8 in TILs was positively correlated with a distant metastasis-free period. The total number of primary TILs (CD4 plus CD8) and CD8 1 primary TILs of stage 3 patients with distant metastases was positively correlated with their overall survival. To evaluate whether CD8 1 effector T cells are activated or differentiated, flow cytometric analysis of peripheral blood mononuclear cells (PBMC) was performed. The percentages of CD8 1 T cells producing IFN-c in PBMC were significantly higher in patients with angiosarcoma (n 5 10) compared not only with that of healthy controls (n 5 20) but also patients with advanced melanoma (n 5 11). These results suggest that anti-tumor immunity is clinically relevant in angiosarcoma.

PurposeProgrammed death-1 (PD-1) or programmed death ligand-1 (PD-L1) targeted therapies have shown promising survival outcomes in several human neoplasms. However, it is unclear whether the expression of PD-L1 can be correlated to any clinical and pathologic variables in patients with cutaneous angiosarcoma (CA). The aim of this study was to evaluate the clinicopathological significance of PD-L1 expression in CA patients.Materials and MethodsData from 52 patients with CA were retrospectively reviewed. PD-L1 expression, tumor proliferation determined by Ki-67 index, and immunohistochemical evaluation of tumor-infiltrating lymphocytes, CD4+ and CD8+, were used to determine correlation with clinicopathological variables.ResultsPD-L1 was positively expressed in 40% of all patients. PD-L1 expression was significantly associated with tumor cell proliferation. Multivariate analysis confirmed that high levels of CD8+ tumor-infiltrating lymphocytes were a significant predictor in patients with clinical stage I CA and the positive expression of PD-L1 was an independent prognostic factor in predicting worse outcome.ConclusionPD-L1 expression is a novel pathologic marker for predicting worse outcome in patients with CA.

Miyako Islands are an endemic area of non-AIDS KS. The high rate of a distinct HHV8 may contribute to the high incidence of KS in the region.

L-type amino acid transporter 1 (LAT1) and CD98 are frequently expressed in various human cancers, and closely correlated with tumor aggressiveness and survival. However, little is known about the expression of LAT1 and CD98 in cutaneous angiosarcoma. The aim of this study is to investigate the clinicopathological significance of these markers in the dismal disease. A total of 52 patients with cutaneous angiosarcoma were retrospectively reviewed. Immunohistochemical staining of tumor specimens were evaluated using anti-LAT1, CD98 and Ki-67 antibodies. The rates of high expression for LAT1 and CD98 were 56% (29/52) and 79% (41/52), respectively. The frequency of high expression for CD98 was significantly higher than that for LAT1 (p=0.021). The low expression of CD98 was significantly associated with distant metastasis (p=0.044) and was identified as a significant prognostic predictor by multivariate analysis. The expression level of LAT1 was not significantly correlated with prognosis. The low expression of CD98 is a novel biomarker for predicting poor prognosis in patients with cutaneous angiosarcoma.