Cell cycle regulatory proteins p27 kip1 , cyclins D1 and E and proliferative activity in oncocytic (Hürthle cell) lesions of the thyroid

Cyclins are prime cell-cycle regulators central to the control of cell proliferation in eukaryotic cells. The formation of cyclin/cyclin-dependent kinases (CDK) complexes activates the kinases and initiates a cascade of events, which directs cells through the cell cycle. CDK inhibitors (CDKIs) such as p27 kip1 inhibit cyclin-CDK complexes and function as negative regulators of the cell cycle. Previous studies have shown that p27 kip1 is decreased in malignant relative to benign thyroid tumors, but its role and interaction with other cell cycle regulatory proteins have not been well established in oncocytic lesions of the thyroid. We studied the expression of p27 kip1 , cyclins D1 and E, and Ki67 in 20 cases of oncocytic adenoma (AD), 6 cases of oncocytic carcinoma (CA), 8 cases of Hashimoto’s thyroiditis (HT), and 9 cases of nodular goiter with oncocytic change (NG) by immunohistochemistry. In the latter two lesions only oncocytic cells were evaluated. The positive staining was stratified into four groups. Statistical analysis was done using the Kruskal-Wallis one-way analysis of variance test, and, when significant, the Dunn multiple-comparisons procedure was used to determine pairwise differences. All 20 AD were p27 kip1 positive, 10 were 4+, 2 were 3+, and the remaining 8 were 1+. In contrast all 6 CA showed 4+ p27 kip1 staining, of the 8 HT, 2 were 4+, two 3+, three 1+, and 1 was negative. All 9 NG were p27 positive, 7 showed 4+, one 3+, and one 1+ staining. On pairwise comparison differences in p27 kip1 staining between AD and CA and between HT and CA were statistically significant ( p =0.0243 and p =0.0142, respectively). In all but one case Ki67 expression was either very low (<3%) or negative. No significant differences were seen in the expression of cyclin D1 or cyclin E among the groups observed. In conclusion, the increased p27 kip1 expression in malignant oncocytic tumors relative to benign oncocytic lesions is unlike any other malignant progression reported in the thyroid and other organ systems in the body. This may reflect on the biologic nature of the oncocytic cells of the thyroid and the significance of this finding remains to be established. Proliferative activity as studied by Ki67 immunostaining was not helpful in distinguishing benign from malignant oncocytic tumors.