Can K-ras codon 12 mutations be used to distinguish benign bile duct proliferations from metastases in the liver? A molecular analysis of 101 liver lesions from 93 patients

• Published in: The American journal of pathology Vol. 151; no. 4; pp. 943 - 949
• Main Authors: Hruban, RH, Sturm, PD, Slebos, RJ, Wilentz, RE, Musler, AR, Yeo, CJ, Sohn, TA, van Velthuysen, ML, Offerhaus, GJ
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.10.1997; American Society for Investigative Pathology
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - genetics; Adenocarcinoma - secondary; Bile Duct Neoplasms - diagnosis; Bile Duct Neoplasms - genetics; Bile Duct Neoplasms - secondary; Bile Ducts - pathology; Biological and medical sciences; Cell Division; Codon - genetics; Diagnosis, Differential; DNA Mutational Analysis; DNA, Neoplasm - analysis; Epithelium - pathology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Liver Neoplasms - diagnosis; Liver Neoplasms - genetics; Liver Neoplasms - secondary; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - genetics; Point Mutation; Proto-Oncogene Proteins p21(ras) - genetics; Tumors; Pseudotumor; Adenocarcinoma; Performance evaluation; Human; Duodenum; Liver; Hepatic disease; Pancreatic head; Malignant tumor; Metastasis; Proliferation; Vater ampulla; Bile canaliculi; Differential diagnostic; Polymerase chain reaction; Pathology; Codon; C-Onc gene; Digestive diseases; Intestinal disease; Mutation; Molecular biology; Protooncogene; Pancreatic disease
• ISSN: 0002-9440; 1525-2191

It can be difficult to distinguish benign bile duct proliferations (BDPs) from well-differentiated metastatic peripancreatic adenocarcinomas on histological grounds alone. Most peripancreatic carcinomas harbor activating point mutations in codon 12 of the K-ras oncogene, suggesting that K-ras mutational status may provide a molecular basis for distinguishing BDPs from liver metastases. The ability of tests for mutations in codon 12 of K-ras to make this distinction was examined in a two-part study. In the first part we determined the K-ras mutational status of 56 liver lesions and 48 primary peripancreatic adenocarcinomas obtained from 48 patients. In the second part of this study an additional 45 liver lesions were studied. In the first 48 patients, activating point mutations in codon 12 of K-ras were detected in 28 (61%) of the 46 primary carcinomas, in 8 (100%) of 8 liver metastases, in 2 (6.5%) of 31 BDPs, and in none (0%) of 14 liver granulomas. Three BDPs and two primary carcinomas did not amplify. To further estimate the prevalence of K-ras mutations in BDPs we analyzed an additional series of 45 mostly incidental BDPs for K-ras mutations. Three (6.7%) of these 45 harbored K-ras mutations. These results suggest that K-ras mutations may be useful in distinguishing BDPs from metastases in the liver; however, there is some overlap in the mutational spectra of BDPs and pancreatic carcinomas.