K-ras mutations in stools and tissue samples from patients with malignant and nonmalignant pancreatic diseases

Abstract

Mutant-enriched PCR and reverse dot blot hybridization in microplates were applied for examining K-ras status in stools and tissue samples from patients with pancreatic tumors and chronic pancreatitis. In tissue samples, K-ras mutations were found in 32 of 35 cases of ductal adenocarcinoma, in 5 of 7 periampullary cancers, in 1 cystadenocarcinoma, and in 3 of 5 patients with chronic pancreatitis. In stools, mutated K-ras was seen in 10 of 25 cases of ductal adenocarcinoma, in 1 case of cystadenocarcinoma, and in 2 of 6 cases of chronic pancreatitis. These data indicate that the K-ras status of stool samples may help identify pancreatic carcinoma and persons at risk for cancer development; however, it does not allow discrimination of malignant from nonmalignant diseases.

Detektion von Mikrometastasen nach kurativer Resektion duktaler Adenokarzinome des Pankreas

“…Voraussetzung für den Einsatz solcher molekularbiologischer Verfahren ist das Vorhandensein definierter Veränderungen der Tumorzelle, welche als Differenzierungen zu Normalzellen dienen können. Beim Adenokarzinom des Pankreas finden sich Mutationen im Kodon 12 des K-ras-Gens in 70 bis 95 % aller Fälle [1,4,5,6,8,14]. Diese Mutationen bieten somit einen hervorragenden Ansatzpunkt zur Detektion einzelner Tumorzellen [4,5,8,9,10,30,32].…”

“…Beim Adenokarzinom des Pankreas finden sich Mutationen im Kodon 12 des K-ras-Gens in 70 bis 95 % aller Fälle [1,4,5,6,8,14]. Diese Mutationen bieten somit einen hervorragenden Ansatzpunkt zur Detektion einzelner Tumorzellen [4,5,8,9,10,30,32]. Ziel dieser Arbeit war der Nachweis einer MRD in paraaortalen Lymphknoten nach kurativer Resektion beim duktalen Adenokarzinom des Pankreas mittels Nachweis von Mutationen im K-ras-Gen.…”

Detection of oncogenes in chronic pancreatitis

“…BRAC2 mutation carriers [66]) and patients with CP [67]. However, the diagnostic value of K‐ras genotyping in stool has been compared to that of tissue samples and the serum tumour markers CA 19‐9 and CEA in pancreatic diseases, while K‐ras genotyping has been found to lack the specificity to discriminate malignant pancreatic disease from chronic inflammation [68–70].…”

“…The analysis of gene mutations and gene expression in pancreatic cancer and CP has identified several factors, which are commonly deregulated in both diseases [54–57]. Detection of mutations in the K‐ras proto‐oncogene and p53 tumour suppressor gene in specimens obtained by needle aspiration, from pure pancreatic juice, duodenal juice, serum or stool, may be clinically useful diagnostic markers for early detection of pancreatic malignancy [58–70]. Although these mutations are considered critical and early events in pancreatic oncogenesis, the role of K‐ras and p53 mutations in CP as a precancerous disorder is not completely known.…”

Stool DNA testing for the detection of pancreatic cancer

“…Mutant KRAS can be sequenced from pancreatic juice from patients with PanC. 12,13 Our group 14 and others 15,16 have demonstrated that mutant KRAS in stool can reflect the presence of both pancreatic cancer and precancer. However, no single mutation marker has optimal coverage of PanC, and panels of mutation markers can be analytically unwieldy for use in routine practice.…”