OBJECTIVES: Evading apoptosis is a hallmark of pancreatic cancer. In pancreatic cancer models, chemotherapy down-regulates the antiapoptotic protein cellular FLICE inhibitory protein (c-FLIP), which renders cells sensitive to apoptosis. Currently, the relevance of c-FLIP expression as a biomarker in pancreatic cancer is unknown, and here we assessed the prognostic significance of the c-FLIP expression status in a large cohort of pancreatic cancer patients with clinical follow-up. METHODS: Cellular FLICE inhibitory protein expression levels were determined by immunohistochemistry in 120 surgically resected ductal pancreatic adenocarcinomas. Survival analysis by c-FLIP status was compared with established clinicopathologic biomarkers as well as Ki-67 and cyclooxygenase 2 expression levels as 2 other established independent prognostic biomarkers in pancreatic cancer. RESULTS: Of 120 tumors, 111 (91%) were c-FLIP positive, whereas 9 (9%) were completely c-FLIP negative. Cyclooxygenase 2 was positive in 59 cases (52%), and Ki-67 was positive in more than 10% of tumor cells in 51 cases (44%). Univariate and multivariate survival analysis (correcting for stage, grade, and proliferation index) showed that c-FLIP is an independent prognostic factor. Specifically, c-FLIP negativity identifies 9% of patients with a highly aggressive disease course (P = 0.0001). CONCLUSIONS: Cellular FLICE inhibitory protein expression status is a valuable prognostic biomarker in pancreatic cancer.
OBJECTIVES: Evading apoptosis is a hallmark of pancreatic cancer. In pancreatic cancer models, chemotherapy down-regulates the antiapoptotic protein cellular FLICE inhibitory protein (c-FLIP), which renders cells sensitive to apoptosis. Currently, the relevance of c-FLIP expression as a biomarker in pancreatic cancer is unknown, and here we assessed the prognostic significance of the c-FLIP expression status in a large cohort of pancreatic cancerpatients with clinical follow-up. METHODS: Cellular FLICE inhibitory protein expression levels were determined by immunohistochemistry in 120 surgically resected ductal pancreatic adenocarcinomas. Survival analysis by c-FLIP status was compared with established clinicopathologic biomarkers as well as Ki-67 and cyclooxygenase 2 expression levels as 2 other established independent prognostic biomarkers in pancreatic cancer. RESULTS: Of 120 tumors, 111 (91%) were c-FLIP positive, whereas 9 (9%) were completely c-FLIP negative. Cyclooxygenase 2 was positive in 59 cases (52%), and Ki-67 was positive in more than 10% of tumor cells in 51 cases (44%). Univariate and multivariate survival analysis (correcting for stage, grade, and proliferation index) showed that c-FLIP is an independent prognostic factor. Specifically, c-FLIP negativity identifies 9% of patients with a highly aggressive disease course (P = 0.0001). CONCLUSIONS: Cellular FLICE inhibitory protein expression status is a valuable prognostic biomarker in pancreatic cancer.
Authors: Wilson Petrushnko; Justin S Gundara; Philip R De Reuver; Greg O'Grady; Jaswinder S Samra; Anubhav Mittal Journal: HPB (Oxford) Date: 2016-07-14 Impact factor: 3.647
Authors: Fenja M Feld; Philipp D Nagel; Stephanie E Weissinger; Claudia Welke; Albrecht Stenzinger; Peter Möller; Jochen K Lennerz Journal: Oncotarget Date: 2015-02-28
Authors: Sandra Wiedenmann; Markus Breunig; Jessica Merkle; Christine von Toerne; Tihomir Georgiev; Michel Moussus; Lucas Schulte; Thomas Seufferlein; Michael Sterr; Heiko Lickert; Stephanie Ellen Weissinger; Peter Möller; Stefanie M Hauck; Meike Hohwieler; Alexander Kleger; Matthias Meier Journal: Nat Biomed Eng Date: 2021-07-08 Impact factor: 25.671