Absence of FLICE-Inhibitory Protein Is a Novel Independent Prognostic Marker for Very Short Survival in Pancreatic Ductal Adenocarcinoma

作者：Schmid Sandra J; Glatzel Marie Charlotte; Welke Claudia; Kornmann Marko; Kleger Alexander; Barth Thomas F E; Fulda Simone; Lennerz Jochen K^*; Moeller Peter

来源：Pancreas, 2013, 42(7): 1114-1119.

• pancreatic cancer
• c-FLIP
• biomarker
• prognostic biomarker
• COX-2

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.

• 出版日期2013-10