Genetic Alterations of K-ras, P53, C-erbB-2, and DPC4 in Pancreatic Ductal Adenocarcinoma and Their Correlation with Patient Survival

Objectives: 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.