关键词: FOXA2 GATA3 Sarcomatoid yolk sac tumor postpubertal-type Somatic-type malignancy Yolk sac tumor postpubertal-type

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

来  源:   DOI:10.1007/s00428-023-03725-0

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.
摘要:
在化疗后的环境中,类似于非特异性肉瘤并共同表达细胞角蛋白和磷脂酰肌醇蛋白聚糖-3(GPC3)的睾丸生殖细胞肿瘤(GCTT)被诊断为“青春期后肉瘤样卵黄囊肿瘤(YSTpt)”。肉瘤样YSTpt的诊断具有临床相关性,但由于其稀有性而具有挑战性。非特异性组织学,和阴性的甲胎蛋白(AFP)染色。最近,FOXA2已成为GCTT重编程的关键基因(激活几种基因的转录,其中GATA3),免疫组织化学研究表明,GATA3和FOXA2对非肉瘤样YSTpt的敏感性高于GPC3和AFP。我们发现肉瘤样YSTpt不表达FOXA2[0:14/14(100%)],并显示GATA3的局灶性表达[0:12/14(85.7%),1+:2/14(14.3%)],因此表明这些标志物在诊断这种肿瘤中没有用。此外,我们提出了GCTT化疗后肉瘤样转化的潜在机制,由FOXA2和GATA3的下调介导。
公众号