Are you Ken Nishikura M.D?

Claim your profile

Publications (2)10.4 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND To investigate their hypothesis that K-ras mutation is correlated with epithelial metaplastic change, the authors classified tumors of the papilla of Vater histologically and according to mucin histochemistry as either intestinal type (complete or incomplete) or pancreaticobiliary type (ordinary or metaplastic) and analyzed the tumors for K-ras mutation during tumorigenesis.METHODS Fifty-two tumors of the papilla of Vater (5 adenomas, 24 carcinomas with adenoma component, and 23 carcinomas) obtained from surgical specimens were evaluated. The mucus phenotype was analyzed with MUC1, MUC2, MUC5AC, sialyl Lewisa (CA 19-9), HID-AB, and ConA III stainings. K-ras codon 12 mutation was detected by nested polymerase chain reaction (PCR)-restriction fragment length polymorphism and enriched PCR-enzyme-linked minisequence assay.RESULTSThe presence of adenoma component and intramucosal tumor spreading in the ampulloduodenum was significantly higher in intestinal-type tumors (90%, 27 of 30 tumors, and 100%, 30 of 30 tumors, respectively) than in pancreaticobiliary-type tumors (9%, 2 of 22 tumors, and 23%, 5 of 22 tumors, respectively) (P < 0.0001). MUC2 expression was positive in intestinal-type tumors but not in pancreaticobiliary-type tumors. K-ras mutation rates for incomplete intestinal-type tumors (78%, 7 of 9) and metaplastic pancreaticobiliary-type tumors (64%, 7 of 11), which showed MUC5AC (gastric-type apomucin) expression in cytoplasm, were significantly higher than in complete intestinal-type tumors (33%, 6 of 21) and ordinary pancreaticobiliary-type tumors (18%, 2 of 11) (P = 0.01 and P = 0.03, respectively). In pancreaticobiliary-type tumors, K-ras mutation was more frequently recognized in tumors with ampullopancreatic duct tumor extension (75%, 3 of 4) than in those with ampullobiliary duct extension (0%, 0 of 6) (P = 0.01). Furthermore, sequences of K-ras codon 12 were common in 17 carcinomas with adenoma component that were analyzed for both adenoma and carcinoma.CONCLUSIONS Tumors of the papilla of Vater can be classified histologically as either intestinal type or pancreaticobiliary type, and they have different features according to tumor location, association with adenoma, and MUC2 expression. Furthermore, K-ras mutation is supposed to be associated with tumors arising in the area from the ampulloduodenum to the ampullopancreatic duct, with metaplastic mucus occurring in both intestinal and pancreaticobiliary types. Cancer 1999;86:596–607. © 1999 American Cancer Society.
    Cancer 11/2000; 86(4):596 - 607. · 5.20 Impact Factor
  • [Show abstract] [Hide abstract]
    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.RESULTSOf 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.
    Cancer 02/1998; 82(4):651 - 660. · 5.20 Impact Factor