K-ras mutation, p53 overexpression, and microsatellite instability in biliary tract cancers: a population-based study in China.
OBJECTIVE
The genetic alterations in biliary tract cancer and clinicopathological associations have not been studied in large population-based studies.


METHODS
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.
Rashid
Asif
A
Department of Pathology and Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. arashid@mdanderson.org
Ueki
Takashi
T
Gao
Yu-Tang
YT
Houlihan
Patrick Scott
PS
Wallace
Charita
C
Wang
Bing-Sheng
BS
Shen
Ming-Chang
MC
Deng
Jie
J
Hsing
Ann W
AW
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D000293:Adolescent; D000328:Adult; D000368:Aged; D001661:Biliary Tract Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D002681:China; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D015996:Survival Rate
D004273:DNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II