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Determination of pancreatic ductal carcinoma histogenesis by analysis of mucous quality and K‐ ras mutation
Author(s) -
Matsubayashi Hiroyuki,
Watanabe Hidenobu,
Nishikura Ken,
Ajioka Yoichi,
Kijima Hiroshi,
Saito Toshihiko
Publication year - 1998
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19980215)82:4<651::aid-cncr6>3.0.co;2-o
Subject(s) - histogenesis , mutation , pathology , hyperplasia , carcinogenesis , mutant , pancreas , carcinoma , biology , microbiology and biotechnology , immunohistochemistry , medicine , endocrinology , cancer , gene , genetics
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. Cancer 1998;82:651‐60. © 1998 American Cancer Society.