This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rashid, A. Articles by Hsing, A. W. Search for Related Content PubMed PubMed Citation Articles by Rashid, A. Articles by Hsing, A. W.

K-ras Mutation, p53 Overexpression, and Microsatellite Instability in Biliary Tract Cancers

A Population-based Study in China

Department of Pathology and Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 [A. R., T. U.]; Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [A. R., P. S. H., C. W.]; Shanghai Cancer Institute, Shanghai, China [Y-T. G., J. D.]; Department of General Surgery, Zhongshan Hospital, Shanghai, China [B-S. W.]; Department of Pathology, Shanghai Cancer Hospital, Shanghai, China [M-C. S.]; and Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892 [A. W. H.]

Purpose: The genetic alterations in biliary tract cancer and clinicopathological associations have not been studied in large population-based studies.

Experimental Design: We evaluated genetic alterations such as K-ras mutation, p53 overexpression, microsatellite instability (MSI), and alterations of the polyadenine tract present in the transforming growth factor ß receptor type II (TGFßRII) gene in 126 biliary tract cancers: 75 gallbladder cancers, 33 bile duct cancers, and 18 ampullary cancers. These genetic alterations were compared with patient demographics and clinicopathological characteristics of the tumors.

Results: Mutation of the K-ras gene was present in 18 of 126 (14.3%) biliary tract cancers. K-ras mutation was present in 11 of 18 (61.1%) ampullary cancers, 5 of 33 (15.2%) bile duct cancers, and 2 of 75 (2.7%) gallbladder cancers (P = 0.000001). The mean survival of patients who had bile duct carcinomas with K-ras mutation was 3.0 ± 2.2 months compared with 15.5 ± 12.5 months for those without mutation (P = 0.03) but was not different for other tumor sites. p53 overexpression was present in 34 of 123 (27.6%) cancers. MSI-high (allelic shifts in 40% or more loci or alteration of the TGFßRII gene) was present in 4 of 126 (3.2%) biliary tract cancers without hereditary nonpolyposis colorectal cancer. MSI-high was more common in mucinous adenocarcinomas (P = 0.006) and in patients with early age of onset of cancer (P = 0.04).

Conclusions: The genetic alterations in biliary tract cancers are dependent on the tumor subsite, histology, and age of onset and are associated with prognosis.

This article has been cited by other articles:

				G. Andreotti, J. Chen, Y.-T. Gao, A. Rashid, B. E. Chen, P. Rosenberg, L. C. Sakoda, J. Deng, M.-C. Shen, B.-S. Wang, et al. Polymorphisms of Genes in the Lipid Metabolism Pathway and Risk of Biliary Tract Cancers and Stones: A Population-Based Case-Control Study in Shanghai, China Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 525 - 534. [Abstract] [Full Text] [PDF]

				K. Soreide and J. A. Soreide Bile Duct Cyst as Precursor to Biliary Tract Cancer Ann. Surg. Oncol., March 1, 2007; 14(3): 1200 - 1211. [Abstract] [Full Text] [PDF]

				M. Varga, P. Obrist, S. Schneeberger, G. Muhlmann, C. Felgel-Farnholz, D. Fong, M. Zitt, T. Brunhuber, G. Schafer, G. Gastl, et al. Overexpression of Epithelial Cell Adhesion Molecule Antigen in Gallbladder Carcinoma Is an Independent Marker for Poor Survival Clin. Cancer Res., May 1, 2004; 10(9): 3131 - 3136. [Abstract] [Full Text] [PDF]