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Titolo:
Cholangiocarcinoma in primary sclerosing cholangitis: K-ras mutations and Tp53 dysfunction are implicated in the neoplastic development
Autore:
Boberg, KM; Schrumpf, E; Bergquist, A; Broome, U; Pares, A; Remotti, H; Schjolberg, A; Spurkland, A; Clausen, OPF;
Indirizzi:
Rikshosp, Dept Med, N-0027 Oslo, Norway Rikshosp Oslo Norway N-0027Rikshosp, Dept Med, N-0027 Oslo, Norway Huddinge Hosp, Karolinska Inst, Dept Gastroenterol & Hepatol, Stockholm, Sweden Huddinge Hosp Stockholm Sweden stroenterol & Hepatol, Stockholm, Sweden Univ Barcelona, Hosp Clin Prov 1, Liver Unit, E-08007 Barcelona, Spain Univ Barcelona Barcelona Spain E-08007 er Unit, E-08007 Barcelona, Spain Sahlgrens Univ Hosp, Dept Pathol, Gothenburg, Sweden Sahlgrens Univ Hosp Gothenburg Sweden , Dept Pathol, Gothenburg, Sweden Rikshosp, Inst Transplantat Immunol, Oslo, Norway Rikshosp Oslo NorwayRikshosp, Inst Transplantat Immunol, Oslo, Norway Univ Oslo, Rikshosp, Inst Pathol, Oslo, Norway Univ Oslo Oslo NorwayUniv Oslo, Rikshosp, Inst Pathol, Oslo, Norway
Titolo Testata:
JOURNAL OF HEPATOLOGY
fascicolo: 3, volume: 32, anno: 2000,
pagine: 374 - 380
SICI:
0168-8278(200003)32:3<374:CIPSCK>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYMERASE CHAIN-REACTION; TUMOR-SUPPRESSOR GENE; LIVER-TRANSPLANTATION; POINT MUTATION; INTRAHEPATIC CHOLANGIOCARCINOMA; PROGNOSTIC FACTORS; NATURAL-HISTORY; HUMAN CANCER; P53; BILIARY;
Keywords:
cholangiocarcinoma; K-ras mutations; Ki-67 immunoreactivity; p53 protein; primary sclerosing cholangitis; tumor markers;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Boberg, KM Rikshosp, Dept Med, N-0027 Oslo, Norway Rikshosp Oslo Norway N-0027 sp, Dept Med, N-0027 Oslo, Norway
Citazione:
K.M. Boberg et al., "Cholangiocarcinoma in primary sclerosing cholangitis: K-ras mutations and Tp53 dysfunction are implicated in the neoplastic development", J HEPATOL, 32(3), 2000, pp. 374-380

Abstract

Background/Aim Cholangiocarcinoma is a feared complication of primary sclerosing cholangitis (PSC), Neoplastic bile duct strictures may be difficult to differentiate cholangiographically from the non-neoplastic bile duct irregularities characteristic of this disorder, and the diagnosis of cholangiocarcinoma may be difficult to establish with certainty, even in tissue samples, Thus, new methods which can improve the diagnostic accuracy of cholangiocarcinoma in PSC are needed. Methods: We investigated the occurrence of IC-Mcs codon 12 and 13 mutations, p53 protein accumulation, and Ki-67 expression in tumor tissue from PSC patients (n=33) who had developed cholangiocarcinoma, using bile duct specimens exised at Liver transplantation of PSC patients without cholangiocarcinoma (n=15) as controls,Results: K-ras mutations were present in 11 (33%) of the cholangiocarcinoma samples and significantly more frequent in females, Nine tumors carried acodon 12 mutation, and 2 had a codon 13 mutation, The most frequent substitutions in codon 12 were GGT --> GAT (n=5) and GGT --> TGT (n=3). None of the control bile ducts had K-ras mutations. p53 protein was accumulated in 10 (31%) of the tumors, as opposed to negative findings in all the control samples, Sixteen (48%) tumors revealed either K-ras mutation or p53 accumulation, Ki-67 positivity was significantly higher in cholangiocarcinomas thanin the non-neoplastic bile duets (median 29% vs 12%, respectively; p=0.011). Conclusion: We conclude that R-vas mutations and p53 dysfunction are implicated in tumorigenesis of cholangiocarcinomas arising in PSC patients and that these abnormalities together with increased Ki-67 index may indicate neoplastic progression of bile ducts in these patients.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 22:38:12