Differential transcriptional and protein expression of thyroid-stimulating hormone receptor in ovarian carcinomas.

OBJECTIVE: Thyroid-stimulating hormone (TSH) regulates normal thyroid function by binding to its receptor (thyroid-stimulating hormone receptor -TSHR) that is expressed at the surface of thyroid cells. Recently, it has been demonstrated that TSHR is abundantly expressed in several tissues apart from the thyroid, among them the normal ovarian surface epithelium. The role of TSHR expression outside the thyroid is not completely understood. The current study examines possible alterations of TSHR expression in ovarian carcinomas and its implication in ovarian carcinogenesis. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction and immunohistochemistry analysis of TSHR expression were performed in 34 ovarian carcinoma specimens and 10 normal ovarian tissues (controls). RESULTS: Significant reduction in TSHR messenger RNA (mRNA) expression was detected in ovarian carcinomas (mean [SD]: 0.518 [0.0934] vs normal, 49.4985 [89.1626]; P < 0.001, Mann-Whitney U test), whereas TSHR protein levels were significantly increased (percentage of positive cells: cancer, 73.55% [20.09%], vs normal, 54.54% [21.14%]; intensity: cancer, 2.52 [0.508], vs normal 1 [0]; P = 0.012, Mann-Whitney U test). No significant differences in TSHR mRNA were found according to history of thyroid disease. CONCLUSIONS: Our study describes for the first time alterations in TSHR expression both at mRNA and protein levels in ovarian carcinomas. The discrepancy between the decreased levels of the TSHR mRNA and the increased protein expression has already been described in thyroid carcinomas and might be due to alterations in its degradation by the ubiquitin system or other unknown mechanisms. Further analysis could elucidate the role of these findings in ovarian carcinogenesis.

Cisplatin-based chemotherapy for advanced seminoma: report of 52 cases treated in two institutions.

INTRODUCTION: We evaluated an intensified therapeutic strategy in order to optimize treatment outcomes while maintaining acceptable toxicity in patients with advanced seminoma. PATIENTS AND METHODS: Fifty-two patients with advanced pure seminoma were retrospectively evaluated. Patients with low-risk advanced seminoma, according to the International Germ Cell Cancer Collaborative Group Consensus Classification criteria, had received four cycles of the BEP regimen either in the 5-day or the alternative 3-day schedule, while patients with intermediate-risk advanced seminoma had received four cycles of the IBEP regimen. RESULTS: Forty-two patients (80.7%) had testicular seminoma while ten patients (19.3%) presented with primary extragonadal (mediastinal or retroperitoneal) tumor. Forty-seven (90.8%) patients belonged to the low-risk group and five patients (9.2%) to the intermediate-risk group. Treatment-related toxicity was moderate, with febrile neutropenia being the most prevalent (13.5%). Twenty patients (38.5%) achieved a complete response to chemotherapy. Twenty-three from the remaining 32 patients had residual masses more than 3 cm and were submitted to surgery (2 patients), FDG-PET scan (8 patients) or surveillance (13 patients). After 69 months of follow-up there were three recurrences that were successfully treated with high-dose or salvage chemotherapy. No death by any cause was recorded. CONCLUSIONS: Intensified cisplatin-based chemotherapy for patients with advanced seminoma does not confer evidence of superiority over radiotherapy alone or the standard BEP regimen. Patients with low-volume abdominal disease (clinical stage IIA and IIB) can be cured by four cycles of BEP instead of radiotherapy at the cost of a substantial increase in chemotherapy exposure and the resulting toxicity.