Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

TY - JOUR

T1 - Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

AU - Ewen, Katherine A

AU - Olesen, Inge A

AU - Winge, Sofia B

AU - Nielsen, Ana Ricci

AU - Nielsen, John E

AU - Graem, Niels

AU - Juul, Anders

AU - Rajpert-De Meyts, Ewa

PY - 2013

Y1 - 2013

N2 - Observations in patients with an activating mutation of fibroblast growth factor receptor 3 (FGFR3) suggest a role for FGFR3 signalling in promoting proliferation or survival of germ cells. In this study, we aimed to identify the FGFR3 subtype and the ontogeny of expression during human testis development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes through-out development for FGFR3 expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis development, expression of FGFR3 did not directly correlate with proliferation markers. In preinvasive CIS cells and in TGCTs, including classical seminoma and embryonal carcinoma, FGFR3IIIc was detected only in a small number of cells, with a heterogeneous expression pattern. FGFR3 is an excellent marker for human pre-/spermatogonia throughout development. Signalling through this receptor is likely associated with spermatogonial survival rather than proliferation. FGFR3 is not expressed in gonocytes and may not be essential to the aetiology of TGCTs stemming from CIS.

AB - Observations in patients with an activating mutation of fibroblast growth factor receptor 3 (FGFR3) suggest a role for FGFR3 signalling in promoting proliferation or survival of germ cells. In this study, we aimed to identify the FGFR3 subtype and the ontogeny of expression during human testis development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes through-out development for FGFR3 expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis development, expression of FGFR3 did not directly correlate with proliferation markers. In preinvasive CIS cells and in TGCTs, including classical seminoma and embryonal carcinoma, FGFR3IIIc was detected only in a small number of cells, with a heterogeneous expression pattern. FGFR3 is an excellent marker for human pre-/spermatogonia throughout development. Signalling through this receptor is likely associated with spermatogonial survival rather than proliferation. FGFR3 is not expressed in gonocytes and may not be essential to the aetiology of TGCTs stemming from CIS.

U2 - 10.1387/ijdb.130022er

DO - 10.1387/ijdb.130022er

M3 - Journal article

C2 - 23784824

SN - 0214-6282

VL - 57

SP - 141

EP - 151

JO - International Journal of Developmental Biology

JF - International Journal of Developmental Biology

ER -