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.