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.