Kyle C Cuneo1, Meredith A Morgan2, Kent A Griffith3, Peter G Hawkins2, Joel K Greenson4, Edgar Ben-Josef5, Theodore S Lawrence2, Mark M Zalupski6. 1. Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. Electronic address: kcuneo@umich.edu. 2. Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. 3. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan. 4. Department of Pathology, University of Michigan, Ann Arbor, Michigan. 5. Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. 6. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Abstract
PURPOSE: To determine the prognostic significance of c-MET expression and develop a predictor of distant failure in patients with resectable pancreatic cancer treated with chemoradiation. METHODS AND MATERIALS: We used a tissue microarray to study protein expression by immunohistochemistry in 102 patients treated surgically for pancreatic cancer. Two cores per patient were blindly scored from 0 (no staining) to 3 (strong staining) by a single pathologist. The Kaplan-Meier method was used to determine time to local and distant failure, overall survival, and progression-free survival. P values were calculated with the log-rank test. RESULTS: High tumor expression of c-MET was associated with a shorter time to distant failure in patients receiving neoadjuvant (n=23) or neoadjuvant therapy (n=73) (median 8.9 months vs 22.0 months, P=.0010). We then examined the ability of incorporating 2 known biomarkers, thymidylate synthase and DPC4 (SMAD4), with c-MET to risk-stratify patients. This multi-protein predictor divided our cohort into groups of similar numbers and was predictive of distant failure (median 13.4 months vs 24.2 months, P=.0094) but not of local control. CONCLUSION: c-MET is potentially predictive of distant failure. Using c-MET, DPC4, and thymidylate synthase, we developed a multi-protein predictor that could be used to risk-stratify patients and guide decisions regarding the sequencing of locoregional and systemic therapies in pancreatic cancer.
PURPOSE: To determine the prognostic significance of c-MET expression and develop a predictor of distant failure in patients with resectable pancreatic cancer treated with chemoradiation. METHODS AND MATERIALS: We used a tissue microarray to study protein expression by immunohistochemistry in 102 patients treated surgically for pancreatic cancer. Two cores per patient were blindly scored from 0 (no staining) to 3 (strong staining) by a single pathologist. The Kaplan-Meier method was used to determine time to local and distant failure, overall survival, and progression-free survival. P values were calculated with the log-rank test. RESULTS:High tumor expression of c-MET was associated with a shorter time to distant failure in patients receiving neoadjuvant (n=23) or neoadjuvant therapy (n=73) (median 8.9 months vs 22.0 months, P=.0010). We then examined the ability of incorporating 2 known biomarkers, thymidylate synthase and DPC4 (SMAD4), with c-MET to risk-stratify patients. This multi-protein predictor divided our cohort into groups of similar numbers and was predictive of distant failure (median 13.4 months vs 24.2 months, P=.0094) but not of local control. CONCLUSION:c-MET is potentially predictive of distant failure. Using c-MET, DPC4, and thymidylate synthase, we developed a multi-protein predictor that could be used to risk-stratify patients and guide decisions regarding the sequencing of locoregional and systemic therapies in pancreatic cancer.
Authors: M Clarke; R Collins; S Darby; C Davies; P Elphinstone; V Evans; J Godwin; R Gray; C Hicks; S James; E MacKinnon; P McGale; T McHugh; R Peto; C Taylor; Y Wang Journal: Lancet Date: 2005-12-17 Impact factor: 79.321
Authors: M Tascilar; H G Skinner; C Rosty; T Sohn; R E Wilentz; G J Offerhaus; V Adsay; R A Abrams; J L Cameron; S E Kern; C J Yeo; R H Hruban; M Goggins Journal: Clin Cancer Res Date: 2001-12 Impact factor: 12.531
Authors: R E Wilentz; G H Su; J L Dai; A B Sparks; P Argani; T A Sohn; C J Yeo; S E Kern; R H Hruban Journal: Am J Pathol Date: 2000-01 Impact factor: 4.307
Authors: Carmen J Allegra; Allyson L Parr; Lester E Wold; Michelle R Mahoney; Daniel J Sargent; Patrick Johnston; Pam Klein; Katie Behan; Michael J O'Connell; Ralph Levitt; John W Kugler; Maria Tria Tirona; Richard M Goldberg Journal: J Clin Oncol Date: 2002-04-01 Impact factor: 44.544
Authors: D H Harpole; M B Moore; J E Herndon; T Aloia; T A D'Amico; T Sporn; A Parr; I Linoila; C Allegra Journal: Clin Cancer Res Date: 2001-03 Impact factor: 12.531
Authors: Erlinda E Embuscado; Daniel Laheru; Francesca Ricci; Ki Jung Yun; Sten de Boom Witzel; Allison Seigel; Katie Flickinger; Manuel Hidalgo; G Steven Bova; Christine A Iacobuzio-Donahue Journal: Cancer Biol Ther Date: 2005-05-12 Impact factor: 4.742
Authors: Ying Chuan Hu; Richard A Komorowski; Shannon Graewin; Galen Hostetter; Olli-P Kallioniemi; Henry A Pitt; Steven A Ahrendt Journal: Clin Cancer Res Date: 2003-09-15 Impact factor: 12.531
Authors: Hunter C Gits; Amy H Tang; William S Harmsen; William R Bamlet; Rondell P Graham; Gloria M Petersen; Thomas C Smyrk; Amit Mahipal; Roman O Kowalchuk; Jonathan B Ashman; William G Rule; Dawn Owen; Michelle A Neben Wittich; Robert R McWilliams; Thorvardur Halfdanarson; Wen Wee Ma; Terence T Sio; Sean P Cleary; Mark J Truty; Michael G Haddock; Christopher L Hallemeier; Kenneth W Merrell Journal: J Gastrointest Oncol Date: 2021-10