K-ras mutations in tissue and stool samples from patients with pancreatic cancer and chronic pancreatitis.

Abstract

K-ras oncogene is the most promising molecular marker of pancreatic cancer. However, the incidence of single and combined K-ras mutations in stool and pancreatic tissue is unknown, and it is not clear whether detection of the K-ras oncogene in stool could be employed in screening tests. Stool and pancreatic tissue of patients with ductal adenocarcinoma (n = 36), cystadenocarcinoma (n = 1), periampullary carcinoma (n = 7), endocrine tumour (n = 2) and chronic pancreatitis (CP, n = 5) were analysed for mutated K-ras sequences prospectively. DNA of stool and pancreatic tissue was amplified by polymerase chain reaction and K-ras status was analysed by hybridisation. K-ras mutations were detected in the pancreatic tissue of 28 patients with ductal adenocarcinoma (78%), in 1 patient with cystadenocarcinoma, in 1 patient with periampullary carcinoma (14%) and in 1 patient with CP (20%). In 1 patient with an endocrine tumour, no K-ras mutations were diagnosed. K-ras mutations were detected in stool in 7 patients with ductal adenocarcinoma (20%), in 1 patient with cystadenocarcinoma and in 2 patients with CP (40%). Sensitivity of K-ras mutations for pancreatic cancer was 78% in tissue and 20% in stool. K-ras mutations lack specificity to discriminate malignant pancreatic disease from chronic inflammation in tissue and stool.