Prognostic significance of p27, Ki-67, and topoisomerase II alpha expression in clinically nonfunctioning pancreatic endocrine tumors

Nonfunctioning islet cell tumors or pancreatic endocrine tumors are the mos t common type of malignant islet cell tumor. Although previously detected u sually at an advanced stage because of mass effect, the early detection rat e of small localized disease has been increasing. To date it has been diffi cult to predict the clinical behavior in localized regional nonfunctioning tumors. To investigate potential markers predicting malignancy and poor pro gnosis in nonfunctioning pancreatic endocrine tumors, we a nalyzed the expr ession of Ki-67, topoisomerase II alpha (Topoll alpha), and p27, as well as a variety of clinicopathologic parameters in 76 cases of nonfunctioning is let cell tumors (23 benign cases and 53 malignant cases). Ki-67, Topoll alp ha, and p27 labeling indices were significantly different between benign an d malignant tumors. Expression of Ki-67, Topolla, and p27 were associated w ith survival in patients with a malignant tumor in a univariate setting. Ho wever, only p27 and Topoll alpha were jointly associated with survival in m ultivariate analysis. Immunohistochemical staining for p27, Topolla, and Ki -67 can be helpful in the diagnosis of nonfunctioning pancreatic endocrine tumor. Analysis of p27 and Topolla may also have potential utility as progn ostic factors for malignant tumors.