Predominant expression of fibroblast growth factor (FGF) 8, FGF4, and FGF receptor 1 in nonseminomatous and highly proliferative components of testicular germ cell tumors

Abstract

Nonseminomatous components within testicular germ cell tumors affect patient prognosis to varying degrees. These components are well known to mimic early embryonic totipotential tissues. Prompted by the recent observation that fibroblast growth factor (FGF) 8, FGF4, and FGF receptor (FGFR) 1 are required for the growth of early postimplantational embryonic tissues, we investigated the expressions of FGF8, FGF4, and FGFRI in surgically resected specimens of primary testicular germ cell tumors using an immunohistochemical method. All cases of embryonal carcinoma (14 cases), yolk sac tumor (3 cases), and choriocarcinoma (3 cases) showed positive immunostaining for FGF8, FGF4, and FGFR1. In contrast, out of 13 cases of seminoma, immunostaining was negative for FGF8, FGF4, and FGFR1 in 8 cases (61.5%), 6 cases (46.1%), and 7 cases (53.8%), respectively. In 7 cases of mature and immature teratoma, most areas showed negative immunostaining. In addition, the Ki-67 labeling index showed extremely high mitogenic activity in embryonal carcinoma, yolk sac tumor, and choriocarcinoma, which are precisely the carcinomas with the highest expressions of FGF8, FGF4, and FGFR1. It is in keeping with the immunohistochemical result that murine teratocarcinoma P19 cells were shown to express FGF8, FGF4, and FGFRI only under undifferentiated growth conditions. Taken together, these findings confirm the involvement of FGF8, FGF4, and FGFR1 in highly proliferative conditions of nonseminomatous germ cell tumors.

Oncofetal protein glypican-3 in testicular germ-cell tumor

“…Pluripotent potential germ-cell neoplasms, like IGCNU, seminoma, and embryonal carcinoma, are labeled with antibodies against PLAP, c-KIT [12], OCT3/4 (POU5F1) [15], and CD30 [18]. On the other hand, for differentiated GCT, several growth factors, growth factor receptors, and transcription factors have been reported in neoplastic cells but with various frequencies and variable specificity [8,11,21]. This study confirmed the outstanding specificity of GPC3 to differentiated GCT, such as in "the double layer pattern", glandular structures of embryonal carcinoma encircled by a row of flattened YST cells [1,3], in MGCT in which OCT3/4 and GPC3 immunoreactivities were mutually exclusive.…”

Fibroblast Growth Factor 8b Causes Progressive Stromal and Epithelial Changes in the Epididymis and Degeneration of the Seminiferous Epithelium in the Testis of Transgenic Mice1

“…Low level of Fgf8 mRNA is also expressed by the epididymis [3]. Interestingly, high levels of FGF8 are expressed in prostatic [20][21][22] and testicular [23] cancers. Previous studies have shown that FGF8 can promote tumorigenic properties, such as growth, invasiveness, and the angiogenic, migratory, and metastatic capacity of breast and prostate cancer cells [24][25][26][27], and can induce tumorigenesis in the mouse prostate [28,29].…”

Fator de crescimento fibroblástico básico e seus receptores em relação à atividade proliferativa na placenta bubalina em diferentes fases da gestação

“…Segundo a literatura, a atividade proliferativa celular pode ser influenciada por outros FGFs: FGF4 (Baczyk et al, 2005;Suzuki et al, 2001), FGF7 (Palmieri et al, 2003), FGF8 (Suzuki et al, 2001;Xu et al, 1998), FGF9 (Miyagi et al, 1999) e FGF10 (Xu et al, 1998 Mol. Cell.…”