Analysis of PD-L1 expression in trophoblastic tissues and tumors

【摘要】：Aims:To investigate Programmed Death Ligand-1(PD-L1) expression and its clinical applications in trophoblastic tumors.Materials Methods:We performed a comprehensive immunohistochemical study of PDL1 expression in a large cohort of trophoblastic tissues and tumors,and Western-blot analysis in 3 trophoblastic cell lines(SWAN-71,JEG-3 and JAR).Results:We found that normal villi and hydatidiform moles showed a heterogeneous PD-L1 staining among trophoblasts(strong in syncytiotrophoblasts,moderate in intermediate trophoblasts,and negative in cytotrophoblasts).Eleven exaggerated placental sites(100%) showed variable PDL1 staining whereas 7/19(36.8%) placental site nodules/plaques were weakly positive for PD-L1(p0.001).All gestational choriocarcinomas(CC, n=63), epitheloid trophoblasitc tumors(ETT, n=12) and placental site trophoblastic tumors(PSTT,n=41) were PD-L1 positive,with most showing strong staining.However,PD-L1 expression was lower in ETTs compared with PSTTs and CCs(p=0.004).Three germ-cell-derived pure CCs,the CC elements in 13 mixed germ-cell tumors and 4 gastric/rectal CCs were also positive for PD-L1,with widespread staining.The background non-trophoblastic tissues,such as endometrial glands,squamous cells,and common adenocarcinomas,were PD-L1 negative.Western-blot analysis showed that PD-L1 was expressed in all 3 trophoblastic cell lines.Conclusions:We conclude that PD-L1 is a potential marker for trophoblastic differentiation,and is helpful in the discrimination of trophoblastic tumors from other cancers.The frequent strong PD-L1 expression suggests that immune checkpoint blockade could be a promising approach in treating trophoblastic tumors that merits further investigation.