Leydig Cell Tumors in Prepubertal Boys: Strong Immunoexpression of Aromtase, Estrogen Receptors and Growth Factors

E BERENSZTEIN, R MARINO, M S BAQUEDANO, M MALOSETTI, G GUERCIO, E VAIANI, BELGOROSKY, MA RIVAROLA

Toronto, Canadá

Congreso; The Endocrine Society's 89th Annual Meeting; 2007

Endocrine Society (ENDO)

Leydig cells (LC) of early postnatal human testes showed strong immunostaining of aromatase (ARO) but weak staining of estrogen receptor alpha (ERa), ER and androgen receptor (AR) (1). The role of estrogens could be to preserve an adequate pool of precursor LC by inhibiting apoptosis. However, an overexpression of ARO results in increased estrogen production and a changed hormone milieu, favoring the induction of testicular tumors (Tu) in experimental animals. On the other hand, in AR deficient mice, fetal LC is normal, but adult LC development fails. Furthermore, the IGF-IR sends a strong anti-apoptotic signal in most tissues. The aim of this study was to describe some characteristics of LCTu in three prepubertal (PP) patients (Pat) in order to understand the physiopathology of these Tu. Three Pat, aged 6.7, 1.6 and 3.8 years (PAT #1, #2 and #3, respectively) were studied. They all had pseudoprecocious puberty and unilateral testicular enlargement. PAT #1 and #3 had moderate gynecomastia. The pathologic diagnosis post orchidectomy was Leydig cell tumor. Expression of P450scc, ARO, ERa and ERb, AR, IGF2, type 1 IGFR, insulin receptor (IR), TGFb and TGFb receptor (TGFb R) was study by immunohistochemistry. LC of non-tumoral testes, collected from 1- to 7- month old PP boys (PPLC), n=12, were also analyzed. P450scc expression was high in LCTu and in PPLC. ARO, ERa (2/3) and ERb expression was high in LCTu. However, no AR expression in LCTu contrasted with detection of expression in PPLC. Moreover, the expression of type 1 IGFR and IR was high in LCTu. Also, a very high expression of the TGFb system was seen in LCTu. The excess of estrogen action and lack of androgen action may stimulate cell proliferation. LCTu proliferation might also be increased by excessive expression of components of the IGF system, as it was described for other Tu. TGFb system overexpression was also detected in several Tu. All these factors might contribute to modulate the growth of LCTu in children.References: (1) Berensztein E, Baquedano MS, Gonzalez CR, Saraco NI, Rodrguez J, Ponzio R, Rivarola MA, Belgorosky A. Expression of aromatase, estrogen receptor alpha and beta, androgen receptor and cP450scc, in the human early prepubertal testis. Pediatr Res. 2006 Dec; 60(6):740-4. Results:(expressed as percentage of positive cells, xES) Antibody PAT #1 PAT #2 PAT #3 PPLC P450scc 69.6 61.6 99.0 97.2 0.70 ER 90.1 < 2.0 80.0 2.1 0.90 ER 88.9 80.0 88.0 8.62.22 ARO 53.6 71.6 52.8 22.1 4.84 AR < 2.0 < 2.0 not done 10 2.34 IGFR 66.1 62.8 53.8 3.04 0.68 IGF-2 30.9 26.8 54.0 38.3 3.72 IR 60.2 60.9 56.0 28.2 3.14 TGF 100 96.4 not done 7.1 3.0 TGFR 99.6 98.1 not done 5.0 1.5