Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 32 P526 | DOI: 10.1530/endoabs.32.P526

ECE2013 Poster Presentations Endocrine tumours and neoplasia (66 abstracts)

Expression of FGF23, Klotho, CaSR, and PTHrP in carcinoma in situ and germ cell tumors of the testis: implications for testicular microlithiasis

Martin Blomberg Jensen , John E Nielsen , Anne Jørgensen , Anders Juul & Ewa Rajpert-De Meyts


Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.


Introduction: Vitamin D (VD) metabolism is active in normal testis, but lost during the malignant progression from carcinoma in situ (CIS) to overt germ cell tumors (TGCTs). CIS and TGCTs are often associated with intratubular deposition of hydroxyapatite (microlithiasis). Imbalance in FGF23 and PTH homeostasis may result in calcification of mesodermal-derived tissue, so we hypothesized that this mechanism may be involved in testicular microlithiasis. Here, we investigated classical regulators of VD metabolism, phosphate and calcium homeostasis: FGF23, CaSR, PTHrP, in addition to their corresponding receptors and downstream mediators in human testis, with and without CIS and TGCT.

Materials and methods: In total, 20 samples of normal adult human testis, 20 CIS, 25 TGCTs and five fetal testes were investigated by qPCR and immunohistochemistry. FGF-23 was measured with an immunoassay in serum and seminal fluid of ten patients with TGCT.

Results: Normal germ cells expressed PTHrP, PTHR, Klotho, FGFR1, FGFR3 and the phosphate transporter NPT2b, but virtually no FGF23 expression was detected. FGF23, CaSR, PTHrP and NPT2a were markedly upregulated (P<0.05) in CIS at RNA and protein level, with a high correlation between CaSR and PTHrP (r=0.91 P<0.005) and a correlation of PTHrP and FGF23 with NPT2a (P<0.01). PTHrP, but not FGF23, was expressed in fetal germ cells. The protein expression of FGF23, CaSR, and PTHrP diminished in invasive TGCTs, and FGF23 levels in serum and seminal plasma were not significantly higher in TGCTs patients compared with controls.

Conclusion: Testicular neoplasia is associated with profound changes in intratesticular VD, calcium and phosphate homeostasis. It remains to be established whether over-expression of FGF23 in CIS is a regulatory mechanism, or reflects genomic amplification associated with malignant transformation, but upregulation of FGF23 may contribute to the formation of testicular microliths in the vicinity of CIS and TGCTs.

Article tools

My recent searches

No recent searches.