Telomerase activity predicts survival in pancreatic endocrine tumors (PETs).

Abstract

Background: Telomerase is an enzyme associated with cellular immortality. Telomerase activity is associated with aggressive tumor behavior and is present in :::=:95% of pancreatic adenocarcinomas. PETs have a variable prognosis and predictors of tumor behavior and patient survival are lacking. AIM: Determine the telomerase activity in PETs and its role as a prognostic indicator. Methods: Telomerase detection with telomeric repeat amplification protocol (TRAP) was performed on frozen surgical archived neuroendocrine tissue from 30 patients with PETs. All results were confirmed with internal controls. Survival was measured from the time of surgery. Results: 3 of 30 PETs were TRAP( +): all 3 were nonfunctional. 2 of 3 TRAP( +) patients had extrapancreatic disease. All 3 patients (mean age 63) died due to tumor progession within 2 yrs of surgery (mean 1.7 :to.5 SD). 27 of 30 PETs were TRAP(-): 13 insulinomas, 4 nonfunctional, 2 glucagonomas, I gastrinoma, I VWoma, I carcinoid-like, 3 MEN-I and 2 Von-Hippel-Lindau. 10 of 27 TRAP(-) had extrapancreatic disease; despite these unfavorable pathological findings, the mean post-operative survival time was 7.0 yrs. Kaplan-Meier survival estimates for TRAP(-) PETs was significantly longer than TRAP( +) PETs (mean 8.6 :t5 yrs vs 1.7 :to.5, P=O.OOOI Log Rank Test, Figure). Conclusions.J) Telomerase activity in PETs is associated with a poor prognosis independent of extrapancreatic metastasis. 2) Telomerase is not found in the majority of PETs and may be responsible for their indolent clinical course.