胰腺导管腺癌中 K-ras、p53、c-erbB-2 和 DPC4 的基因改变及其与患者生存的相关性。

Genetic alterations of K-ras, p53, c-erbB-2, and DPC4 in pancreatic ductal adenocarcinoma and their correlation with patient survival.

机构信息

Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

出版信息

Pancreas. 2013 Mar;42(2):216-22. doi: 10.1097/MPA.0b013e31825b6ab0.

DOI:10.1097/MPA.0b013e31825b6ab0

PMID:23344532

Abstract

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.

摘要

目的

本研究旨在评估胰腺导管腺癌中 K-ras、p53、c-erbB-2 和 DPC4 基因的遗传改变，并将这些改变与患者的总生存相关联。

方法

在 2004 年 4 月至 2008 年 12 月期间，在一家医院进行了 272 例胰腺导管腺癌手术切除患者的回顾性研究。对基因分析和免疫组织化学染色进行了回顾。

结果

每个基因的改变率如下：K-ras，53.8％；p53，38.2％；c-erbB-2，7.3％；DPC4，81.6％。K-ras 基因的亚型如下：GGT（野生型），46.2％；GAT，31.2％；GTT，14.5％；CGT，5.6％；TGT，1.7％；CTG，0.4％；AGT，0.4％。K-ras 突变（尤其是 GAT 亚型）和 DPC4 失活导致术后生存时间缩短（P=0.001 和 P=0.047）。单因素分析显示 8 个因素影响患者的生存，多因素分析显示其中 6 个因素独立影响患者的不良预后：存在血管淋巴管肿瘤栓子、DPC4 失活、低分化癌、K-ras 突变、存在淋巴结转移和 CA-19-9 升高（>37 U/mL）。