title: An assessment of chromosomal alterations detected by fluorescence in situ hybridization and p16 expression in sporadic and primary sclerosing cholangitis-associated cholangiocarcinomas.
abstract: The objective of this study was to assess and compare the chromosome abnormalities present in sporadic and primary sclerosing cholangitis (PSC)-associated cholangiocarcinomas (CCAs) and biliary dysplasias. Histologic sections from 22 patients with CCA (16 sporadic and 6 PSC associated), 5 of whom had associated dysplasia, and 2 PSC patients with biliary dysplasia alone were assessed for chromosomal alterations with fluorescence in situ hybridization (FISH). FISH involved the use of a multiprobe set consisting of centromere-specific probes for chromosomes 3, 7, and 17 and a locus-specific probe for 9p21. The number of signals for each of these probes was enumerated in 50 nonoverlapping interphase nuclei, and the percentage of nuclei containing 0, 1, 2, and 3 or more signals was recorded for each probe. p16 expression was assessed using immunohistochemistry. Gain of at least 1 chromosome was identified in 19 of 22 (86%) invasive tumors and in 4 of 7 (57%) biliary dysplasias. Gain of 2 or more chromosomes (polysomy) was observed in 17 of 22 (77%) invasive tumors and in 3 of 7 (43%) biliary dysplasias. Homozygous loss of 9p21 was identified in 11 of 22 (50%) invasive tumors and in 3 of 7 (43%) biliary dysplasias. The patterns of chromosomal abnormalities detected by FISH in PSC-associated and sporadic CCAs were similar. Nine of 13 (69%) invasive tumors and 2 of 5 (40%) biliary dysplasias with complete loss of p16 expression by immunohistochemistry showed allelic loss of 9p21 by FISH. Polysomy and homozygous 9p21 deletion are common in both sporadic and PSC-associated CCAs and are frequently detectable in PSC-associated biliary dysplasia.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: DeHaan
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Kipp
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
authors.forename: Susan C
authors.initials: SC
authors.lastname: Abraham
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Roberts
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Halling
mesh_terms: D000328:Adult; D000368:Aged; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D018281:Cholangiocarcinoma / Q000150:complications* / Q000235:genetics; D015209:Cholangitis, Sclerosing / Q000150:complications* / Q000235:genetics; D002869:Chromosome Aberrations; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16