Luisa Di Sciascio

Analysis of HNF1β expression suggests that its downregulation is involved in the sarcomatoid transformation of yolk sac tumor

Sarcomatoid yolk sac tumor postpubertal-type (YSTpt) is a rare phenotype of germ cell tumor that occurs mostly after chemotherapy. Its diagnosis is clinically relevant but challenging, due to its somewhat inconspicuous histologic features and negative/low expression of classical YSTpt makers (α-fetoprotein (AFP), glypican-3 (GPC3), and GATA3)). HNF1β is likely a key inducer of the YSTpt phenotype, acting in part by regulating the binding of FOXA2 to its target genomic sequences. Recently, immunohistochemical studies have shown that HNF1β has a sensitivity comparable to FOXA2 (higher than GPC3 and AFP) for non-sarcomatoid YSTpt. We found that sarcomatoid YSTpt did not express HNF1β (0: 8/8 (100%)), suggesting that combined downregulation of FOXA2 and HNF1β may underlie the sarcomatoid transformation in this rare phenotype of germ cell tumor.