Analysis of GATA3 and FOXA2 expression suggests that downregulation of genes involved in the maintenance of a mature yolk sac tumor phenotype may underlie sarcomatoid transformation

Virchows Arch. 2024 Apr;484(4):709-713. doi: 10.1007/s00428-023-03725-0. Epub 2023 Dec 23.

Abstract

In the post-chemotherapy setting, germ cell tumors of the testis (GCTT) that resemble non-specific sarcomas and co-express cytokeratins and glypican-3 (GPC3) are diagnosed as "sarcomatoid yolk sac tumor postpubertal-type (YSTpt)". The diagnosis of sarcomatoid YSTpt is clinically relevant but challenging due to its rarity, non-specific histology, and negative α-fetoprotein (AFP) staining. Recently, FOXA2 has emerged as a key-gene in the reprogramming of GCTT (activating the transcription of several genes, among which GATA3), and immunohistochemical studies showed that GATA3 and FOXA2 have a higher sensitivity for non-sarcomatoid YSTpt than GPC3 and AFP. We found that sarcomatoid YSTpt did not express FOXA2 [0: 14/14 (100%)] and showed focal expression of GATA3 [0: 12/14 (85.7%), 1 + : 2/14 (14.3%)], thus suggesting that these markers are not useful in diagnosing this tumor. Furthermore, we proposed a potential mechanism of sarcomatoid transformation in the post-chemotherapy setting of GCTT, mediated by the downregulation of FOXA2 and GATA3.

Keywords: FOXA2; GATA3; Sarcomatoid yolk sac tumor postpubertal-type; Somatic-type malignancy; Yolk sac tumor postpubertal-type.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Down-Regulation*
  • Endodermal Sinus Tumor* / genetics
  • Endodermal Sinus Tumor* / metabolism
  • Endodermal Sinus Tumor* / pathology
  • GATA3 Transcription Factor* / genetics
  • GATA3 Transcription Factor* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glypicans / genetics
  • Glypicans / metabolism
  • Hepatocyte Nuclear Factor 3-beta* / genetics
  • Hepatocyte Nuclear Factor 3-beta* / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasms, Germ Cell and Embryonal / genetics
  • Neoplasms, Germ Cell and Embryonal / metabolism
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Phenotype*
  • Sarcoma / genetics
  • Sarcoma / metabolism
  • Sarcoma / pathology
  • Testicular Neoplasms* / genetics
  • Testicular Neoplasms* / metabolism
  • Testicular Neoplasms* / pathology
  • Young Adult

Substances

  • GATA3 Transcription Factor
  • Hepatocyte Nuclear Factor 3-beta
  • GATA3 protein, human
  • FOXA2 protein, human
  • Biomarkers, Tumor
  • Glypicans