Alterations of p16 and prognosis in biliary tract cancers from a population-based study in China.
OBJECTIVE
Biliary tract cancer is an uncommon malignancy with a poor survival rate. We evaluated p16 gene alteration as a prognostic marker for this disease.


METHODS
We studied p16 gene alterations by sequencing, methylation, and loss of heterozygosity of chromosome 9p in 118 biliary tract carcinomas, including 68 gallbladder cancers, 33 extrahepatic bile duct cancers, and 17 ampullary cancers. Survival was evaluated in 57 patients with gallbladder carcinomas, 27 with bile duct carcinomas, and 16 with ampullary carcinomas with and without somatic p16 alterations detected by two different methods.


RESULTS
p16 gene alterations including silent mutations were present in 61.8% gallbladder cancers, 54.5% bile duct cancers, and 70.6% ampullary cancers. p16 gene nonsilent mutations, p16 methylation, and loss of chromosome 9p21-22 that targets p14, p15, and p16 genes were present in 13 of 53 (24.5%), 8 of 54 (14.8%), and 32 of 44 (72.7%) gallbladder tumors; 5 of 25 (20.0%), 5 of 31 (16.1%), and 12 of 21 (57.1%) bile duct tumors; and 3 of 13 (23.1%), 6 of 15 (40.0%), and 8 of 16 (50.0%) ampullary tumors, respectively. The mean survival of patients with gallbladder cancers without p16 alterations was 21.5 +/- 14.8 months compared with 12.1 +/- 11.4 months for patients with p16 alterations (P = 0.02).


CONCLUSIONS
Alteration of p16 gene alone or in combination with alterations of other tumor suppressor genes on chromosome 9p is a prognostic indicator in gallbladder carcinoma, with more favorable survival rates associated with carcinomas lacking p16 gene alterations.
Ueki
Takashi
T
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Hsing
Ann W
AW
Gao
Yu-Tang
YT
Wang
Bing-Sheng
BS
Shen
Ming-Chang
MC
Cheng
Jiarong
J
Deng
Jie
J
Fraumeni
Joseph F
JF
Rashid
Asif
A
D001483:Base Sequence; D001661:Biliary Tract Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002681:China; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D006801:Humans; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors
D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D004273:DNA, Neoplasm