title: E2F-1 transcription factor is overexpressed in oxyphilic thyroid tumors.
abstract: In thyroid tumors, several cell cycle regulators have been found to be altered or overexpressed, but no data exist on E2F transcription factors. Such factors (E2F-1 in particular) act as the final effectors in the retinoblastoma pathway but are also involved in apoptosis. To analyze E2F-1 expression in thyroid neoplasms, we investigated 73 thyroid tumors, including 28 oxyphilic and 45 nonoxyphilic lesions, by immunohistochemistry, in parallel with other cell cycle-related proteins (p27, pRb, p53, and Ki67). p27, Ki-67, pRb, and p53 expression patterns generally overlapped the literature data. E2F-1 was expressed in all thyroid tumor types, both benign and malignant, with no statistical correlation with proliferative status (except for anaplastic carcinoma). A significantly higher percentage of tumor cells expressed E2F-1 in oxyphilic adenomas (71.5%) and oxyphilic carcinomas (66.1%) as compared with that of the corresponding nonoxyphilic lesions (30.8% and 34.5%, respectively; P < .05). These same tumors had a relatively low proliferative index. Therefore, because oxyphilic tumors of the thyroid show peculiar morphological, phenotypic, and ultrastructural features, possibly related to their particular metabolic conditions, it is possible that E2F-1 overexpression is linked to activities other than cell cycle entry in oxyphilic tumors. In conclusion, E2F-1 is expressed in both benign and malignant thyroid tumors, thus suggesting a wide involvement of the retinoblastoma pathway in thyroid tumorigenesis. In addition, in oxyphilic tumors, more than two thirds of tumor cells express E2F-1, an event possibly linked to proapoptotic rather than proliferative signals in such neoplasms.
authors.affiliation: Department of Biomedical Sciences and Oncology, University of Turin, Torino, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Sabrina
authors.initials: S
authors.lastname: Croce
authors.forename: Carla
authors.initials: C
authors.lastname: Pecchioni
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D018249:Adenoma, Oxyphilic / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D002452:Cell Count; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors; C413374:p27 antigen