Expression of p21cip1, p27kip1, and p16INk4a Cyclin-Dependent Kinase Inhibitors in Papillary Thyroid Carcinoma: Correlation with Clinicopathological Factors

Abstract

In a variety of human malignancies, aberrant expression of proteins involved in the control of cell-cycle progression has been reported. In this study, p21cip1, p27kip1, and p16INk4a cyclin-dependent kinase inhibitors were analyzed to evaluate their usefulness in clinical management of papillary thyroid carcinoma (PTC). Archived material derived from 46 cases of PTC was analyzed immunohistochemically. Protein expression was ascertained on tissue microarrays, and results were correlated with clinicopathological features of the patients. Positive immunostaining was observed in 14 (30,4%) p21cip1, 26 (56,5%) p27kip1, and 14 (30,4%) p16INk4a cases. No significant correlation between p21cip1 or p27kip1 and clinical factors was found. In contrast, p16INk4a expression showed a significant correlation with initial extension of the disease. Therefore, 45.8% of patients with loco-regional extension were p16INk4a positive, whereas overexpression was only seen in 15.7% of cases with intrathyroid disease (p < 0.05). Moreover, all patients with simultaneous p16INk4a positivity and lack of p27kip1 staining (four patients) presented lymph node metastases. In contrast, only 12 (28.5%) of the remaining patients showed lymph node tumor involvement. In conclusion, p16INk4a expression suggests extrathyroid neck extension of PTC. This effect is enhanced when p27kip1 is negative. We think that their analysis by immunohistochemistry could be useful in the management of patients with PTC.

Comparative Analysis of Protein Expression in Differentiated Thyroid Tumours: A Multicentre Study

“…Up-regulation of FHIT, p16 and PPAR-γ have also been shown to result in cell-cycle arrest and apoptosis. 13 -15 Previous studies have demonstrated low to absent p16 or FHIT immunoreactivity in thyroid carcinomas 4,16 and, in the present study, their expression in thyroid carcinomas was found to be low. Conversely their expression has been found to be uniformly high in other benign endocrine tumours.…”

Oncogenic Kras Requires Simultaneous PI3K Signaling to Induce ERK Activation and Transform Thyroid Epithelial Cells In vivo

“…Although it is possible that p14/p16 up-regulation represents a thyrocyte's attempt to counter the hyperproliferative signals generated by Kras and PI3K, additional studies are warranted to fully understand this finding. Nonetheless, it is worthy of note that CDKN2A up-regulation has been frequently reported in thyroid carcinomas (26-28). …”

The Immunocytochemistry Is a Valuable Tool in the Diagnosis of Papillary Thyroid Cancer in FNA's Using Liquid-Based Cytology

“…According to recent research, several diagnostic and prognostic markers have been proposed in improving the diagnostic accuracy of papillary thyroid cancer such as Cytokeratin-19 (CK-19), HBME-1, Galectin-3, CD44, CD56, E-cadherin, c-erbB-2, p21 cip1 , p27 kip1 , and p16 ink4a [4–13]. …”