Y-chromosome identification by PCR and gonadal histopathology in Turner's syndrome without overt Y-mosaicism

OBJECTIVE The frequency of gonadoblastoma is high in patients with Turner's syndrome bearing cells with Y or partial Y-chromosome, About 60% of patien ts with Turner's syndrome have a 45,X karyotype, In 30% of them a Y-sequenc e is disclosed by DNA analysis. To identify patients at risk of developing gonadoblastoma, a PCR based assay with SRY, ZFY and DYZ, specific primers w as carried out to detect different Y-sequences in the DNA of peripheral lym phocytes from patients with Turner's syndrome, DESIGN AND PATIENTS Peripheral blood karyotypes from 36 patients with Turne r's syndrome were studied, Patients with proven Y-chromosomal material were excluded, Genomic DNA was extracted from peripheral blood, SRY and ZFY gen es and DYZ(3) repetion of Y-chromosome were amplified by PCR, Patients with clinical signs of hyperandrogenism or with positive Y-sequences by PCR und erwent gonadectomy, The gonadal tissues were examined for Y-sequences using PCR, morphology and immunohistochemical study, MEASUREMENTS Turner's syndrome and signs of hyperandrogenism were evaluated both clinically and through laboratory tests, Haematoxylin and eosin stain ing was employed in gonadal morphology studies, The presence of testosteron e was detected by immunohistochemistry using a monoclonal antibody, RESULTS Two patients who had Y-positive blood samples and three hyperandrog enic (2 hirsutes, 1 virilized) Y-negatives underwent gonadectomy, PCR was c arried out on their gonadal tissue, The tissue from the two patients withou t hyperandrogenism was Y-positive, The gonadal tissue from the three hypera ndrogenics was Y-negative. Gonadal morphology disclosed hilus cell hyperpla sia in the 3 hyperandrogenic Y-negatives and in one Y-positive patient; str omal luteoma and hyperthecosis in the virilized patient, cystadenofibroma i n one hirsute patient and gonadoblastoma in one Y-positive, Testosterone wa s detected immunohistochemically in the hilus cell hyperplasia, stromal lut eoma and hyperthecosis found in the hyperandrogenic patients. CONCLUSIONS The molecular study was sensitive and useful in the evaluation of patients at risk of developing gonadoblastoma. Other nontumour, gonadotr ophin-dependent and Y-independent mechanisms which deserve the same medical approach may be involved in the genesis of hyperandrogenic signs in Turner 's syndrome.