ABSTRACT
Cyclin D1 and E2F-1 proteins are essential for the regulation of the G1/S transition through the cell cycle. Cyclin D1, a product of the bcl-1 gene, phosphorylates the retinoblastoma protein, releasing E2F-1, which in turn activates genes involved in DNA synthesis. Expression patterns of E2F-1 protein in thyroid proliferations have not been reported. This study used monoclonal antibodies for cyclin D1 and E2F-1 proteins to immunostain sections of normal thyroid, hyperplastic (cellular) nodules, follicular adenomas, follicular carcinomas, and papillary carcinomas. The proliferation rate was examined using an antibody specific for the Ki-67 antigen. Fluorescence in situ hybridization (FISH) methods and chromosome 11-specific probes were also employed to determine chromosome copy number and to assess for evidence of amplification at the 11q13 locus in papillary and follicular carcinomas with cyclin D1 overexpression. Concurrent overexpression of Ki-67, cyclin D1, and E2F-1 was found in the majority of benign and malignant thyroid lesions, compared with normal thyroid tissue. Cyclin D1 up-regulation was not due to extra copies of chromosome 11, or bcl-1 gene amplification. Malignant tumours showed the highest expression for all three markers, particularly papillary carcinomas. E2F-1 was detected at the same or slightly lower levels than cyclin D1. It was only found when cyclin D1 was overexpressed. Because cyclin D1 normally activates E2F-1, up-regulation of cyclin D1 may lead to E2F-1 overexpression in benign and malignant thyroid lesions.
Subject(s)
Cell Cycle Proteins/metabolism , DNA-Binding Proteins , Neoplasm Proteins/metabolism , Thyroid Neoplasms/metabolism , Adenocarcinoma, Follicular/metabolism , Adenocarcinoma, Follicular/pathology , Adenoma/metabolism , Adenoma/pathology , Carcinoma, Papillary/metabolism , Carcinoma, Papillary/pathology , Cell Division , Cyclin D1/metabolism , E2F Transcription Factors , E2F1 Transcription Factor , Humans , Hyperplasia/metabolism , In Situ Hybridization, Fluorescence , Ki-67 Antigen/metabolism , Thyroid Gland/pathology , Thyroid Neoplasms/pathology , Transcription Factors/metabolismABSTRACT
BACKGROUND: Ovarian neoplasms, other than sex cord--stromal tumors, are rare causes of hyperandrogenism. Only two cases of primary mucinous carcinomas associated with virilization have been reported. CASE: A 50-year-old female was referred to our clinic with a large pelvic mass. On examination she had significant facial hirsutism, clitoromegaly, and male pattern pubic hair growth. Serum levels of testosterone and dihydroepiandrosterone sulfate were elevated. A 30-cm, multilocular, solid and cystic, left ovarian mass was resected. Histology revealed moderately to poorly differentiated mucinous cystadenocarcinoma. The ovarian stroma contained florid proliferation of luteinized cells. The right ovary showed cortical stromal hyperplasia. Abnormal hormone values normalized 10 days postoperatively. CONCLUSION: We report a rare case of mucinous cystadenocarcinoma with virilization, review the literature, and discuss the mechanisms of hormone production by these tumors.
