Matsubara Toshiki, Sakurai Yoichi, Zhi Li-Zhu, Miura Hirotake, Ochiai Masahiro, Funabiki Takahiko
Department of Surgery, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
J Hepatobiliary Pancreat Surg. 2002;9(3):312-21. doi: 10.1007/s005340200035.
BACKGROUND/PURPOSE: We investigated the molecular mechanisms of carcinogenesis in the biliary epithelium in patients with pancreaticobiliary maljunction.
Point mutations of the K- ras gene and the p53 gene, and the overexpression of p53 gene products were examined in the cancerous and noncancerous biliary epithelium of 37 patients with pancreaticobiliary maljunction, with or without biliary dilatation.
In the gallbladder epithelium of 5 patients with pancreaticobiliary maljunction associated with biliary carcinoma, K- ras gene mutations were detected in 3 (60%), p53 gene mutations in 3 (60%), and the overexpression of p53 gene products in 4 (80%), while in the bile duct epithelium of these patients, these features were found in 2 of 3 (66.7%), in all of 3 (100%), and none of 3 (0%) specimens, respectively. In the gallbladder epithelium of patients with pancreaticobiliary maljunction without biliary carcinoma, K- ras gene mutations were detected in 8 of 24 (33.3%) specimens, p53 gene mutations were detected in 16 of 27 specimens (59.3%), and the overexpression of p53 protein was detected in 5 of 27 (18.5%) specimens, while in the bile duct epithelium of these patients, these features were found in 10 of 25 (40%) specimens, 14 of 25 (56%) specimens, and 6 of 24 (25%) specimens, respectively.
These results suggest that noncancerous lesions of the biliary epithelium in patients with pancreaticobiliary maljunction have mutations of the K- ras gene and/or the p53 gene, which provides genetic evidence that biliary epithelium has high carcinogenic potential.
背景/目的：我们研究了胰胆管合流异常患者胆管上皮细胞癌变的分子机制。
对37例胰胆管合流异常患者，无论有无胆管扩张，其癌性和非癌性胆管上皮细胞进行K-ras基因和p53基因的点突变以及p53基因产物过表达情况的检测。
在5例合并胆管癌的胰胆管合流异常患者的胆囊上皮细胞中，检测到3例（60%）有K-ras基因突变，3例（60%）有p53基因突变，4例（80%）有p53基因产物过表达；而在这些患者的胆管上皮细胞中，分别在3例中的2例（66.7%）、3例全部（100%）、3例均无（0%）标本中发现上述特征。在无胆管癌的胰胆管合流异常患者的胆囊上皮细胞中，24例中的8例（33.3%）标本检测到K-ras基因突变，27例标本中的16例（59.3%）检测到p53基因突变，27例中的5例（18.5%）标本检测到p53蛋白过表达；而在这些患者的胆管上皮细胞中，分别在25例中的10例（40%）标本、25例中的14例（56%）标本、24例中的6例（25%）标本中发现上述特征。
这些结果表明，胰胆管合流异常患者胆管上皮的非癌性病变存在K-ras基因和/或p53基因突变，这为胆管上皮具有高致癌潜能提供了遗传学证据。
