The DPC4/SMAD4 genetic status determines recurrence patterns and treatment outcomes in resected pancreatic ductal adenocarcinoma: A prospective cohort study.
OBJECTIVE
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.
Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Sang Hyun
SH
Shin
Department of Preventive Medicine, University of Ulsan College of Medicine, Seoul, South Korea.
Hwa Jung
HJ
Kim
Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Dae Wook
DW
Hwang
Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Jae Hoon
JH
Lee
Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Ki Byung
KB
Song
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea.
Eunsung
E
Jun
Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
In Kyong
IK
Shim
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Seung-Mo
SM
Hong
Department of Radiology and the Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Hyoung Jung
HJ
Kim
Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Kwang-Min
KM
Park
Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Young-Joo
YJ
Lee
Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Song Cheol
SC
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D051901:Smad4 Protein / Q000235:genetics*; D055815:Young Adult
D014408:Biomarkers, Tumor; C497796:SMAD4 protein, human; D051901:Smad4 Protein
DPC4; SMAD4; pancreatic cancer; pancreatic ductal adenocarcinoma