The novel hormone INSL3 is expressed in human testicular Leydig cell tumors: a clinical and immunohistochemical study

Insulin-like 3 (INSL3) is a novel peptidic hormone member of the relaxin-insulin-like family of peptide factors. It is almost exclusively produced by Leydig cells within the testis and participates to the complex mechanisms leading to physiological testicular descent during embryonic development. We performed a retrospective study evaluating clinical and histopathological characteristics of 13 patients surgically treated for testicular tumor and diagnosed to be affected by Leydig cell tumor (LCT). Furthermore, it was possible to retrieve the archived paraffin embedded tumor together with neighboring healthy testicular tissue of all subjects affected by LCT (12 benign and 1 malignant form), that were analyzed for INSL-3 expression. Immunohistochemical analysis of the tumor sections of the 13 patients affected by LCT demonstrated constitutive expression of INSL3 protein in all LCT, irrespective of the histological pattern of each LCT and with no significant differences of staining intensity between all tumors. In particular, no gross differences were evident between the staining for INSL3 in the 12 benign LCTs and the only one showing malignant clinical behavior. The present study shows that LCTs, a very rare form of testicular tumor with no proven specific serum and histological markers, express a novel member of the relaxin-insulin-like family of peptide factors previously identified as a secretory product of Leydig cells and named INSL3. Thus, there could be the possibility to evaluate the expression and secretion of this novel hormone as a marker of this rare testicular tumor.