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Cancer. 1999 Apr 15;85(8):1703-10.

The K-ras mutation pattern in pancreatic ductal adenocarcinoma usually is identical to that in associated normal, hyperplastic, and metaplastic ductal epithelium.

Author information

1
Department of Pathology, University of Kiel, Germany.

Abstract

BACKGROUND:

Hyperplastic ductal lesions of the pancreas are believed to represent precursors of ductal adenocarcinoma. The most frequent mutation in manifest ductal carcinoma of the pancreas is the K-ras mutation at codon 12. The frequency and significance of this mutation in precursor lesions are a matter of controversy.

METHODS:

The study included 35 resection specimens of ductal adenocarcinoma of the head of the pancreas and 3 noncancerous, noninflammatory pancreases. Ductal lesions were classified according to established criteria. Single cells from these lesions were microdissected and analyzed by the denaturing gradient gel electrophoresis polymerase chain reaction method.

RESULTS:

All primary adenocarcinomas showed a K-ras mutation at codon 12 (25 cases with GAT, 7 cases with GTT, and 3 cases with CGT). One hundred and six of 364 ductal lesions were positive for the mutation. The highest relative percentage (53%) occurred in adenomatoid hyperplasia, followed by 36% in papillary hyperplasia, 26% in mucinous hypertrophy, and 14% in squamous metaplasia. With only two exceptions the mutation pattern of the ductal lesions and that of the corresponding primary tumor were identical. Twenty-one samples from normal ducts (17%) also harbored the K-ras mutation, as did 3 lesions from noncancerous specimens.

CONCLUSIONS:

K-ras mutations are common events in normal, hyperplastic, metaplastic, and neoplastic pancreatic ductal cells. Because K-ras mutations frequently, although not exclusively, are related to mucinous differentiation of pancreatic cells, this mutation may not cause but only promote mucinous differentiation. The prevalence of a certain mutation pattern in nonneoplastic and neoplastic ductal cells in an individual pancreas suggests the dominance of one carcinogenic factor.

PMID:
10223563
[Indexed for MEDLINE]

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