An assessment of chromosomal alterations detected by fluorescence in situ hybridization and p16 expression in sporadic and primary sclerosing cholangitis-associated cholangiocarcinomas

Ryan D. DeHaan, Benjamin R. Kipp, Thomas C. Smyrk, Susan C. Abraham, Lewis R. Roberts, Kevin C. Halling

Research output: Contribution to journalArticle

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)491-499
Number of pages9
JournalHuman Pathology
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2007

Keywords

  • Bile duct
  • Biliary tract
  • Dysplasia
  • FISH
  • Primary sclerosing cholangitis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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