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Medline ® Abstract for Reference 12

of 'Pathology of exocrine pancreatic neoplasms'

K-ras mutation in focal proliferative lesions of human pancreas.
Terhune PG, Phifer DM, Tosteson TD, Longnecker DS
Cancer Epidemiol Biomarkers Prev. 1998;7(6):515.
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 mutationsin 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.
Department of Pathology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.