Abstract
The expression of several growth factors and K-ras gene mutation in bile were studied to better understand the pathogenesis and improve early diagnosis of bile duct cancers. Bile samples were collected from 12 cholangiocarcinomas (CLC), 10 ampullary cancers (APC), 3 gallbladder cancers (GBC), 7 pancreatic cancers (PNC), 9 biliary tract infection (BTI), 8 biliary stone disease (ST), and 5 normal controls (NC). The highest mean value of TGF-β in bile was in patients with BTI; the mean levels of bFGF and PDGF were highest in CLC, and patients with APC and CLC had higher expression of HER2/Neu than other groups. In bile, a K-ras gene codon 12 mutation was found in 5 of 6 (83%) cases of CLC by the PCR-RFLP method. The results suggest overexpression of bFGF, PDGF, and HER2/Neu and the presence of K-ras mutation are important for carcinogenesis of bile duct cancers, and detection of the above abnormalities in bile is helpful for early diagnosis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Nakayama F, Soloway RD, Nakama T, Miyazaki K, Ichimiya H, Sheen PC, Ker CG, Ong GB, Choi TK, Boey J: Hepatolithiasis in East Asia. Retrospective study. Dig Dis Sci 31:21–26, 1986
Su CH, Lui WY. P'eng FK: Relative prevalence of gallstone diseases in Taiwan. A nationwide cooperative study. Dig Dis Sci 37:764–768, 1992
Su WC, Chan KK, Lin XZ, Lin PW, Chow NH, Shin JS, Chen CY, Tsao CJ: A clinical study of 130 patients with biliary tract cancers and periampullary tumors. Oncology 53:488–493, 1996
Chen PH, Lo HW, Wang CS, Tsai KR, Chen YC, Lin KY, Siauw CP, Hwang RR, Liu MH, Ko HC: Cholangiocarcinoma in hepatolithiasis. J Clin Gastroenterol 6:539–547, 1984
Chen MF, Jan YY, Wang CS, Hwang TL, Jeng LB, Chen SC, Chen TJ: A reappraisal of cholangiocarcinoma in patient with hepatolithiasis. Cancer 71:2461–2451, 1993
Koga A, Ichimiya H, Yamaguchi K, Miyazaki K, Nakayama F: Hepatolithiasis associated with cholangiocarcinoma. Possible etiologic significance. Cancer 55:2826–2829, 1985
Marx J: Many gene changes found in cancer [news]. Science 246:1386–1388, 1989
Yukawa M, Fujimori T, Hirayama D, Idei Y, Ajiki T, Kawai K, Sugiura R, Maeda S, Nagasako K: Expression of oncogene products and growth factors in early gallbladder cancer, advanced gallbladder cancer, and chronic cholecystitis. Hum Pathol 24:37–40, 1993
Tada M, Omata M, Ohto M: High incidence of ras gene mutation in intrahepatic cholangiocarcinoma. Cancer 69:1115–1118, 1992
Levi S, Urbano-Ispizua A, Gill R, DM, Gilbertson J, Foster C, Marshall CJ: Multiple K-ras codon 12 mutations in cholangiocarcinomas demonstrated with a sensitive polymerase chain reaction technique. Cancer Res 51:3497–502, 1991
Imai M, Hoshi T, Ogawa K: K-ras codon 12 mutations in biliary tract tumors detected by polymerase chain reaction denaturing gradient gel electrophoresis. Cancer 73:2727–2733, 1994
Watanabe M, Asaka M, Tanaka J, Kurosawa M, Kasai M, Miyazaki T: Point mutation of K-ras gene codon 12 in biliary tract tumors. Gastroenterology 107:1147–1153, 1994
de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM: Biliary tract cancers. N Engl J Med 341:1368–1378, 1999
Friedman SL: Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies. N Engl J Med 328:1828–1835, 1993
Attisano L, Wrana JL, Lopez-Casillas F, Massague J: TGFbeta receptors and actions. Biochim Biophys Acta 1222:71–80, 1994
Heldin CH, Miyazono K, ten Dijke P: TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 390:465–471, 1997
Kretzschmar M, Doody J, Timokhina I, Massague J: A mechanism of repression of TGFbeta/Smad signaling by oncogenic Ras. Genes Dev 13:804–816, 1999
Oft M, Peli J, Rudaz C, Schwarz H, Beug H, Reichmann E: TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev 10:2462–2477, 1996
Goggins M, Shekher M, Turnacioglu K, Yeo CJ, Hruban RH, Kern SE: Genetic alterations of the transforming growth factor beta receptor genes in pancreatic and biliary adenocarcinomas. Cancer Res 58:5329–5332, 1998
Hahn SA, Bartsch D, Schroers A, Galehdari H, Becker M, Ramaswamy A, Schwarte-Waldhoff I, Maschek H, Schmiegel W: Mutations of the DPC4/Smad4 gene in biliary tract carcinoma. Cancer Res 58:1124–1126, 1998
Chow NH, Cheng KS, Lin PW, Chan SH, Su WC, Sun YN, Lin XZ: Expression of fibroblast growth factor-1 and fibroblast growth factor-2 in normal liver and hepatocellular carcinoma. Dig Dis Sci 43:2261–2266, 1998
Tsai TF, Yauk YK, Chou CK, Ting LP, Chang C, Hu CP, Han SH, Su TS: Evidence of autocrine regulation in human hepatoma cell lines. Biochem Biophys Res Commun 153:39–45, 1988
Chow NH, Huang SM, Chan SH, Mo LR, Hwang MH, Su WC: Significance of c-erbB-2 expression in normal and neoplastic epithelium of biliary tract. Anticancer Res 15:1055–1059, 1995
Hayashi K, Takahashi, Kimura K, Nishida W, Saga H, Sobue K: Changes in the balance of phosphoinositide 3–kinase/ protein kinase B (Akt) and the mitogen-activated protein kinases (ERK/p38MAPK) determine a phenotype of visceral and vascular smooth muscle cells. J Cell Biol 145:727–740, 1999
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Su, WC., Shiesh, SC., Liu, HS. et al. Expression of Oncogene Products HER2/Neu and Ras and Fibrosis-Related Growth Factors bFGF, TGF-β, and PDGF in Bile from Biliary Malignancies and Inflammatory Disorders. Dig Dis Sci 46, 1387–1392 (2001). https://doi.org/10.1023/A:1010619316436
Issue Date:
DOI: https://doi.org/10.1023/A:1010619316436