Prognostic Impact of P16 and P21 on Gastroenteropancreatic Neuroendocrine Tumors

Aberrant expression of the cell cycle kinase inhibitors, p16 and p21, has been associated with poor prognosis in a number of human malignancies. These proteins may also be involved in the development and progression of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The present study aimed to investigate protein levels of p16 and p21 in GEP-NETs and to evaluate their clinical significance. p16 and p21 protein expression was tested immunohistochemically in the tissue samples of 68 GEP-NETs. The association between expression and clinicopathological characteristics and overall survival was assessed. Low expression of p16 (no positive nuclear staining) was found in 37 (54%) cases and high p21 expression (≥5% positive nuclear staining) was detected in 23 (34%) cases. Low p16 protein levels indicated a poorer prognosis for patients graded as G2 subgroup in the univariate analysis (relative risk, 4.4; 95% CI, 1.8-10.6). No significant correlation was found between the expression of p21 and any of the clinicopathological variables. The present study indicates a prognostic relevance for p16 immunoreactivity. Low levels of p16 protein were associated with a shorter survival in the G2 subgroup of GEP-NETs. p21 protein expression was not identified to be useful as a predictive indicator in GEP-NETs.