The DPC4/SMAD4 genetic status determines recurrence patterns and treatment outcomes in resected pancreatic ductal adenocarcinoma: A prospective cohort study

// Sang Hyun Shin 1, * , Hwa Jung Kim 2, * , Dae Wook Hwang 1 , Jae Hoon Lee 1 , Ki Byung Song 1 , Eunsung Jun 3 , In Kyong Shim 4 , Seung-Mo Hong 5 , Hyoung Jung Kim 6 , Kwang-Min Park 1 , Young-Joo Lee 1 , Song Cheol Kim 1 1 Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea 2 Department of Preventive Medicine, University of Ulsan College of Medicine, Seoul, South Korea 3 Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea 4 Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea 5 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea 6 Department of Radiology and the Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea * These authors have contributed equally to this work Correspondence to: Song Cheol Kim, email: drksc@amc.seoul.kr Keywords: pancreatic ductal adenocarcinoma, pancreatic cancer, DPC4, SMAD4 Received: October 02, 2016     Accepted: December 31, 2016     Published: January 30, 2017 ABSTRACT Objectives: The objective of this study was to investigate the role of genetic status of DPC4 in recurrence patterns of resected pancreatic ductal adenocarcinoma (PDAC). Methods: Between April 2004 and December 2011, data on patients undergoing surgical resection for PDAC were reviewed. Genetic status of DPC4 was determined and correlated to recurrence patterns and clinical outcomes. Results: Analysis of 641 patients revealed that genetic status of DPC4 was associated with overall survival and was highly correlated with recurrence patterns, as inactivation of the DPC4 gene was the strongest predictor of metastatic recurrence (odds ratio = 4.28). Treatment modalities for recurrent PDAC included chemotherapy alone and concurrent chemotherapy along with local control. For both locoregional and metastatic recurrence, local control resulted in improved survival; however, for groups subdivided according to recurrence patterns and genetic status of DPC4 , local control contributed to improved survival in locoregional recurrences of patients with expressed DPC4 , while chemotherapy alone was sufficient for others. Conclusions: Genetic status of DPC4 contributes to the recurrence patterns following pancreatectomy, and patients with an initially expressed DPC4 gene receive a greater benefit from intensive local control for locoregional recurrence. The DPC4 gene, therefore, may aid the establishment of treatment strategies for initial adjuvant treatment or for recurrent PDAC.