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

• DOI: 10.1007/s00428-025-04062-0
• Publication Date: 2025-02-24T07:51:20Z
• Authors: Costantino Ricci; Sofia Melotti; Luisa Di Sciascio; Francesca Ambrosi; Marco Grillini; Veronica Mollica; Michelangelo Fior...; Antonio De Leo; Muhammad T. Idrees; Thomas M. Ulbright; Andres Martin Acosta
• Keywords: Malignant Transformation; Expression (computer science)

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 (alpha-fetoprotein (AFP), glypican-3 (GPC3), and GATA3)). HNF1 beta 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 HNF1 beta has a sensitivity comparable to FOXA2 (higher than GPC3 and AFP) for non-sarcomatoid YSTpt. We found that sarcomatoid YSTpt did not express HNF1 beta (0: 8/8 (100%)), suggesting that combined downregulation of FOXA2 and HNF1 beta may underlie the sarcomatoid transformation in this rare phenotype of germ cell tumor.