Prognostic Impact of Cyclin D1, Cyclin E and P53 on Gastroenteropancreatic Neuroendocrine Tumours

Conventional classifications of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are rather unsatisfactory because of the variation in survival within each subgroup. Molecular markers are being found able to predict patient outcome in more and more tumours. The aim of this study was to characterize the expression of the proteins cyclin D1, cyclin E and P53 in GEP-NETs and assess any prognostic impact. Tumor specimens from 68 patients with a complete follow-up were studied immunohistochemically for cyclin D1, cyclin E and P53 expression. High cyclin D1 and cyclin E immunostaining (>= 5% positive nuclei) was found in 48 (71%) and 24 (35%) cases, and high P53 staining (>= 10% positive nuclei) in 33 (49%). High expression of P53 was more common in gastric neuroendocrine tumors and related to malignant behavior, being associate with a worse prognosis on univariate analysis (RR=1.9, 95% CI=1.1-3.2). High expression of cyclin E was significantly associated with shorter survival in the univariate analysis (RR=2.0, 95% CI=1.2-3.6) and multivariate analysis (RR=2.1, 95% CI=1.1-4.0). We found no significant correlation between the expression of cyclin D1 and any clinicopathological variables. Our study indicated a prognostic relevance for cyclin E and P53 immunoreactivity. Cyclin E may be an independent prognostic factor from the 2010 WHO Classification which should be evaluated in further studies.