Genetic alterations of K-ras, p53, c-erbB-2, and DPC4 in pancreatic ductal adenocarcinoma and their correlation with patient survival.
OBJECTIVE
The objective of this study was to evaluate genetic alterations of K-ras, p53, c-erbB-2, and deleted in pancreatic cancer, locus 4 (DPC4) genes in pancreatic ductal adenocarcinoma and correlate these changes with patients' overall survival.


METHODS
Between April 2004 and December 2008, 272 patients with pancreatic ductal adenocarcinoma underwent surgical resection at a single institute. Genetic analyses and immunohistochemical stains were reviewed retrospectively.


RESULTS
Alterational rates of each gene were as follows: K-ras, 53.8%; p53, 38.2%; c-erbB-2, 7.3%; DPC4, 81.6%. Subtypes of K-ras gene were as follows: GGT (wild type), 46.2%; GAT, 31.2%; GTT, 14.5%; CGT, 5.6%; TGT, 1.7%; CTG, 0.4%; AGT, 0.4%. K-ras mutation (especially GAT subtype) and DPC4 inactivation resulted in a reduction of postresection survival (P = 0.001 and P = 0.047). Univariate analysis revealed 8 factors affecting to the survival, and multivariate analysis revealed that 6 of them were independently responsible for poor survival of patients: presence of lymphovascular tumor emboli, DPC4 inactivation, poorly differentiated carcinoma, K-ras mutation, presence of lymph node metastasis, and elevated CA-19-9 (>37 U/mL).


CONCLUSIONS
This study may help to understand the genetic feature of pancreatic cancer and its survival effect in our population. This shows that additional genetic insights would contribute to the improvement of patients' prognosis.
Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
Sang Hyun
SH
Shin
Song Cheol
SC
Kim
Seung-Mo
SM
Hong
Young Hoon
YH
Kim
Ki-Byung
KB
Song
Kwang-Min
KM
Park
Young-Joo
YJ
Lee
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D018395:CA-19-9 Antigen / Q000097:blood; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D051901:Smad4 Protein / Q000032:analysis / Q000235:genetics*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D051901:Smad4 Protein; D016159:Tumor Suppressor Protein p53; D018631:ras Proteins; C117307:KRAS protein, human; C497796:SMAD4 protein, human; C495901:TP53 protein, human; C508053:ERBB2 protein, human