Expression of cell-cycle regulators (cyclin D1, cyclin E, p27^kip1, p57^kip2) in papillary thyroid carcinoma

Objective: To evaluate the expression of cell-cycle regulators in papillary thyroid carcinoma in relation to lymph node metastatic features, and to determine whether immunohistochemical staining of cell-cycle markers can predict lymph node metastasis. Study Design: Cross-sectional study of prior surgical specimens. Setting: Academic tertiary referral center. Subjects and Methods: We reviewed the clinical records of patients who had undergone surgery for thyroid cancer and follicular adenoma between January 2005 and May 2008 at our clinic. Among these cases, 92 patients, comprising 28 patients with follicular adenoma, 32 with papillary thyroid carcinoma without lymph node metastasis, and 32 with papillary thyroid carcinoma with lymph node metastasis, were selected randomly. Formalin-fixed, paraffin-embedded tissues from the 92 patients were immunohistochemically stained for cyclin D1, cyclin E, p27^kip1, and p57^kip2, and protein expression levels were quantified and compared among the groups. Results: Tumor specimens from the papillary thyroid carcinoma group had significantly higher expression levels of cyclin D1 and cyclin E, and cytoplasmic expression of p57^kip2 than the other two groups (P < 0.05). In particular, all malignant cases expressed cyclin D1, and cytoplasmic p57^kip2 was expressed only in malignant cases. Furthermore, differences in the grade of cyclin D1 expression according to lymph node metastasis were statistically significant (P < 0.05). Conclusion: Our results suggest that immunohistochemistry of certain cell-cycle regulators may be helpful in the diagnosis of papillary thyroid carcinoma, and that cyclin D1 in particular may be a useful marker for evaluating lymph node metastasis.