K-ras mutation in focal proliferative lesions of human pancreas.
The K-ras gene is mutated in > or =75% of human pancreatic adenocarcinomas and in a number of hyperplastic ductal lesions from noncarcinoma patients. In this study, the incidence of K-ras mutation was determined in a spectrum of focal proliferative pancreatic lesions to evaluate their preneoplastic significance. PCR-based mutation-enriched RFLP analysis was used to identify mutations in codon 12. Immunostaining for Ki67 and p53 was also performed. Forty-seven % of intraductal nonpapillary hyperplasias (8 of 17) contained codon 12 mutations, as did 55% of adenomatoid hyperplasias (6 of 11). This rate increased to 61% in papillary hyperplasias (27 of 44) and to 78% when there was severe dysplasia (7 of 9). The fraction of cells staining for the Ki67 proliferation marker showed a general correlation with the rate of K-ras mutation. Nuclear staining for p53 protein was seen only in two ductal lesions with severe dysplasia. No mutations were found in normal acinar tissue (n = 38), squamous metaplasia (n = 13), ductal complexes (n = 8), or focal acinar cell dysplasia (n = 5). There seemed to be a general correlation of proliferative potential with the presence of K-ras mutation in ductal lesions. However, because of the high prevalence of lesions with K-ras mutations, we conclude that this mutation alone cannot be taken as proof of significant risk for progression to carcinoma. Efforts to use the presence of K-ras mutations in DNA harvested from pancreatic juice or duodenal aspirates as an approach for diagnosis of occult pancreatic carcinoma seem vulnerable to a high false-positive rate.
Terhune
P G
PG
Department of Pathology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
Phifer
D M
DM
Tosteson
T D
TD
Longnecker
D S
DS
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D017931:DNA Primers; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010182:Pancreatic Diseases / Q000175:diagnosis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests
D014408:Biomarkers, Tumor; D017931:DNA Primers