Prognostic Value of c-MET Expression in Patients With Pancreatic Cancer Receiving Adjuvant and Neoadjuvant Chemoradiation Therapy

Publication date: 1 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 2
Author(s): Kyle C. Cuneo, Meredith A. Morgan, Kent A. Griffith, Peter G. Hawkins, Joel K. Greenson, Edgar Ben-Josef, Theodore S. Lawrence, Mark M. Zalupski
PurposeTo 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 MaterialsWe 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.ResultsHigh 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.Conclusionc-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.



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