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 beta receptor type II (TGFbetaRII) 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 TGFbetaRII 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.
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 beta receptor type II (TGFbetaRII) 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 TGFbetaRII 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.
Authors: Xue-Hong Zhang; Gabriella Andreotti; Yu-Tang Gao; Jie Deng; Enju Liu; Asif Rashid; Kai Wu; Lu Sun; Lori C Sakoda; Jia-Rong Cheng; Ming-Chang Shen; Bing-Sheng Wang; Tian-Quan Han; Bai-He Zhang; Gloria Gridley; Joseph F Fraumeni; Ann W Hsing Journal: Int J Cancer Date: 2006-06-15 Impact factor: 7.396
Authors: Gabriella Andreotti; Jinbo Chen; Yu-Tang Gao; Asif Rashid; Bingshu E Chen; Philip Rosenberg; Lori C Sakoda; Jie Deng; Ming-Chang Shen; Bing-Sheng Wang; Tian-Quan Han; Bai-He Zhang; Meredith Yeager; Robert Welch; Stephen Chanock; Joseph F Fraumeni; Ann W Hsing Journal: Cancer Epidemiol Biomarkers Prev Date: 2008-02-22 Impact factor: 4.254