Determination of pancreatic ductal carcinoma histogenesis by analysis of mucous quality and K-ras mutation.

Abstract

BACKGROUND:

The authors sought to elucidate the histogenesis of pancreatic ductal carcinoma by correlating K-ras mutation with mucus type in normal epithelium, mucous cell hyperplasia (MCH), and carcinoma.

METHODS:

Seventy-four solid-type carcinomas (SCs), 23 ductectatic-type carcinomas (DCs), and specimens of 24 normal pancreata were studied. By histochemical staining, normal duct epithelia, areas of MCH, and carcinomas were classified as having sulfo-type or sialo-type mucus. Foci from normal, DC, SC, sulfo-type, or sialo-type specimens were assessed for K-ras mutation at codon 12 by nested polymerase chain reaction and restriction fragment length polymorphism.

RESULTS:

Of the SCs, 9 were sulfo-type and 65 were sialo-type; all DC specimens were sialo-type, and all normal epithelia were sulfo-type. All foci of sulfo-type, nonneoplastic epithelia were negative for K-ras mutation. In contrast, 124 of 313 sialo-type MCH foci (40%) had a K-ras mutation. Of 74 SCs, only 3 of 9 sulfo-type tumors (33%) were positive for the mutation. Sixty of 65 sialo-type SCs (92%) had a K-ras mutation, whereas 15 of 23 sialo-type DCs (65%) had a mutation. K-ras mutant carcinomas (including both SCs and DCs) were associated with K-ras mutant MCH in 109 of 198 MCHs (55%), whereas carcinomas without a K-ras mutation had mutations in 6 of 68 MCHs (9%). MCH in normal pancreata revealed K-ras mutations in 9 of 51 foci (18%). In addition, in K-ras mutant carcinomas, frequency of K-ras mutation in MCH increased from 27% (11 of 41 foci) of nonpapillary MCHs to 62% (98 of 157 foci) of papillary MCHs; but in K-ras wild-type carcinoma, the mutation rate in MCH was unchanged from 12% (3 of 26 foci) to 7% (3 of 42 foci) in nonpapillary and papillary foci, respectively.

CONCLUSIONS:

These results suggest a strong relationship between the risk of pancreatic carcinoma and the presence of combinations of K-ras gene mutation, papillary growth, and expression of sialomucin in foci of MCH.

• Authors: H Matsubayashi, H Watanabe, K Nishikura, Y Ajioka, H Kijima, T Saito
• Journal: Cancer (Cancer) Vol. 82 Issue 4 Pg. 651-60 (Feb 15 1998) ISSN: 0008-543X [Print] United States
• PMID: 9477096 (Publication Type: Journal Article)

Chemical References

• DNA, Neoplasm
• Mucins
• HRAS protein, human
• Proto-Oncogene Proteins p21(ras)

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Ductal, Breast (genetics, metabolism, pathology)
• DNA, Neoplasm (analysis)
• Female
• Genes, ras (genetics)
• Humans
• Hyperplasia (genetics, metabolism, pathology)
• Male
• Middle Aged
• Mucins (metabolism)
• Mucous Membrane (metabolism, pathology)
• Pancreatic Ducts (metabolism, pathology)
• Pancreatic Neoplasms (genetics, metabolism, pathology)
• Phenotype
• Point Mutation
• Polymerase Chain Reaction
• Proto-Oncogene Proteins p21(ras) (metabolism)