Do testis germinal tumours express PTTG (Pituitary Transforminf Tumour Gene)

Introduction and scope: PTTG1 is a mammalian securine that facilitates sister-chromatid separation during metaphase and plays a critical role in chromosomal stability. Levels of PTTG1 mRNA among adult rat tissues are detectable in testicular tissue. PTTG1 may be important as a molecular marker in a variety of cancer. In this study, we analyzed the expression pattern of the immunohistochemical expression of PTTG1 in a series of 30 testicular seminoma.Material and Methods: Testicular tissues from 30 male patients underwent to therapeutic orchidectomy from 2006 to 2010, were examined. All tumours were pure seminomas without any other germ cell tumour component. We also included 2 normal testes from orchiectomy specimens for penile cancer in 2 male patients as control samples. Immunoistochemical results from PTTG1 staining were assessed. The staining intensity was evaluated with three-tiered grading system (0=negative; 1=weak; 2=strong). The percentage of positive cells was calculated and reported as average ± SD. We therefore evaluated PTTG1 predominant cellular pattern of immunostaining (cytoplasmic vs nuclear). We therefore calculated the difference between the percentage of cellular elements positive for PTTG1 in the center and the periphery of the tumor, as a gradient center/periphery.Results: In normal testis the immunostaining of PTTG1 in normal testis was mainly located in the cytoplasm and in the nuclei of spermatocites and spermatids, whereas only weak immunostaining was observed in Leydig cells. In all cases of seminoma examined, PTTG1 staining was located in the nuclear and cytoplasm of neoplastic cells. All PTTG1-positive elements observed in the central area of the tumor display cytoplasmic staining. 12 out of 28 (42.8%) cases presented a prominent nuclear staining in the cellular elements in the periphery of seminoma; the remaining 16 cases showed cytoplasmic staining in these elements. The first group showed significantly higher periphery/center gradient than the group with cytoplasmic staining.In testicular carcinoma in situ (CIS), isolated cells were positive for PTTG1 adjacent to seminoma and in tubules with IGCNU, with prevalent cytoplasmic staining, IGCNU presented very focal immunostaining for PTTG1, occurring in approximately 20% of all tumor elements.Conclusions: In this study we described neoplastic cells PTTG1 positives with nuclear and cytoplasmatic staining in seminoma, and for the first time in IGCNU. PTTG1 showed a significantly expressed protein in seminomas with a caratheristic pattern. In all seminomas a different distribution of PTTG1 positives cells was observed within the tumor with the peripherical areas. PTTG1 is strongly expressed in seminoma cells as well as, for the first time, in its intraepithelial precursor stage called IGCNU. These data suggested that PTTG1 can be used for the detection and diagnosis of IGCNU and this could provide new therapeutic approaches in the management of seminoma.