Alterations of p16INK4A, Rb and cyclin D1 in papillary thyroid carcinoma

Introduction: The tumor-suppressor Rb in its hypophosphorylated form acts as a cell cycle regulator for G1 arrest and abnormalities in the p16/cyclin D1/Rb pathway has been thought to be important in human neoplasia. p16INK4A is inactivated by several different ways including hypermethylation of the promoter. The aim of this study was to assess the relationship between expressions of p16INK4A, Rb and cyclin D1 and methylation status of p16INK4A in papillary thyroid cancer.

Materials and Methods: Thirty six surgically resected papillary thyroid carcinoma cases at Dongsan medical center, Keimyung university from 2003 to 2005 were included in this study. We examined the promoter hypermethylation of p16INK4A and evaluated immunohistochemical analysis of p16INK4A, Rb and cyclinD1 expression.

Results: Aberrant hypermethylation of 5’ CpG islands of the p16 gene promoter was detected in 17(47.2%) of 36 cases. Rb immunostaining was detected in 10(27.8%) of 36 cases and p16INK4A protein was lost in 18(50%) of 36 cases. Overexpression of cyclinD1 immunostaining was found in 27(75%) of 36 cases. There was an inverse relationship between Rb and p16INK4A immunostaining (p<0.026), and was a strong direct correlation between Rb and CyclinD1 immunostaining (p<0.0001). With the exception of a case, p16INK4A promoter hypermethylation correlated significantly with loss of p16INK4A protein expression in papillary thyroid carcinoma (p<0.0001).

Conclusions: These data suggest that promoter hypermethylation is a major mechanism in the inactivation of p16INK4A in papillary thyroid carcinoma. Furthermore, alterations in the p16/CyclinD1/Rb pathway are supposed to be very important in papillary thyroid carcinoma.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA