Apoptosis, proliferation, and FAS/FASL expression in pancreatic adenocarcinoma

ABSTRACT

Deregulation of normal cell cycle machinery is integral to neoplastic growth. There is now compelling evidence implicating the loss of cell kinetic balance in the development and progression of most human cancers, including pancreatic carcinoma which caries extremely poor prognosis. Understanding the pathogenesis of pancreatic cancer seems to be of great value in order to determine the mechanisms of the aggressive growth and metastasis. As the tumor growth depends upon the balance between apoptosis and proliferation, herein, we analyzed by immunohistochemistry the expression of Fas and FasL in 20 operative specimens of pancreatic ductal adenocarcinoma. The apoptotic index [AI] was evaluated by TUNEL in relation to the proliferation index [PI] as estimated by Ki67 aiming to correlate [AI and PI] with clinicopathologic variables and apoptosis-regulating proteins Fas and Fas-L. Fas and FasL were inversely correlated and were detected in 40% and 65% of cases respectively. The mean apoptotic index [AI] was 1.40 +/- 0.74%, and the mean proliferation index [PI] was 42.7 +/- 14%. Fas and AI were closely associated and decreased significantly in higher tumor grade and stage; whereas, FasL and PI increased significantly in higher grade and stage. Tumor infiltrating lymphocytes [TIL] showed higher mean apoptotic index in FasL positive than FasL negative tumor tissues. Therefore, it could be suggested that the apoptotic and proliferation indices could be useful prognostic markers in pancreatic ductal adenocarcinoma. Fas expression plays a key role in apoptosis in pancreatic cancer and FasL expressing carcinomas induce marked apoptosis in TIL allowing them to evade immune surveillance. Therefore, we recommend designing new therapeutic approaches for pancreatic adenocarcinoma based on reinforcement of Fas/FasL-induced tumor apoptosis