Accumulation of p27(kip1) is associated with cyclin D3 overexpression in the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma

Background: The down regulation of protein p27(kip1) ( p27) in most cases of thyroid cancer has relevant diagnostic and prognostic implications. However, the oxyphilic ( Hurthle cell) variant of follicular thyroid carcinoma expresses more p27 than benign oxyphilic lesions do. Aim: To evaluate the mechanism underlying this difference in expression of p27. Methods: Because high levels of cyclin D3 lead to p27 accumulation in cell lines and clinical samples of thyroid cancer, the immunocytochemical pattern of cyclin D3 in oxyphilic ( n = 47) and non- oxyphilic ( n = 70) thyroid neoplasms was investigated. Results: In the whole study sample, there was a significant correlation between p27 and cyclin D3 expression ( Spearman's r: 0.64; p < 0.001). The expression of cyclin D3 and p27 was significantly higher in the oxyphilic variant of follicular carcinomas than in non- oxyphilic carcinomas ( p < 0.001). In the former, cyclin D3 overexpression and p27 accumulation were observed in a median of 75% and 55% of cells, respectively. In co- immunoprecipitation experiments, the level of p27- bound cyclin D3 was much higher in oxyphilic neoplasias than in normal thyroids and other thyroid tumours. Conclusion: These results show that increased p27 expression in the oxyphilic ( Hurthle cell) variant of follicular thyroid carcinoma results from cyclin D3 overexpression.