Chromosome 9p21 loss and p16 inactivation in primary sclerosing cholangitis-associated cholangiocarcinoma

Steven A. Ahrendt, Claus F. Eisenberger, Lin Yip, Asif Rashid, John T. Chow, Henry A. Pitt, David Sidransky

Research output: Contribution to journalArticle

Abstract

Background. Cholangiocarcinoma is a frequent complication of primary sclerosing cholangitis and is a leading cause of mortality in patients with this disease. The tumor suppressor gene p16 is commonly inactivated in many neoplasms; however, the role of p16 in the pathogenesis of cholangiocarcinoma is unclear. Therefore, we examined the role of p16 inactivation in the pathogenesis of cholangiocarcinoma associated with primary sclerosing cholangitis. Materials and methods. Paraffin-embedded sections from 10 patients who developed cholangiocarcinoma in the setting of primary sclerosing cholangitis were examined. Chromosomal loss at 9p21 was determined using microsatellite analysis. Methylation of a CpG island in the promoter region of the p16 gene was determined using methylation-specific polymerase chain reaction. p16 inactivation was also determined using immunohistochemistry. Results. Allelic loss at chromosome 9p21 was present in 9 of 10 tumors (90%). Methylation of the p16 promoter was present in 2 of the 8 tumors examined (25%). Four of seven tumors (57%) analyzed by immunohistochemistry demonstrated an absence of p16 nuclear staining. Conclusions. Loss of chromosome 9p21 and inactivation of the p16 tumor suppressor gene are common events in primary sclerosing cholangitis- associated cholangiocarcinoma and may play a role in the high incidence of cholangiocarcinoma in patients with primary sclerosing cholangitis.

Original languageEnglish (US)
Pages (from-to)88-93
Number of pages6
JournalJournal of Surgical Research
Volume84
Issue number1
DOIs
StatePublished - Jun 1 1999

Fingerprint

Sclerosing Cholangitis
Cholangiocarcinoma
Chromosomes
Methylation
Tumor Suppressor Genes
Neoplasms
Immunohistochemistry
p16 Genes
CpG Islands
Loss of Heterozygosity
Genetic Promoter Regions
Paraffin
Microsatellite Repeats
Staining and Labeling
Polymerase Chain Reaction
Mortality
Incidence

Keywords

  • Biliary tract tumors
  • Cholangiocarcinoma
  • Chromosome 9p21
  • P16
  • Primary sclerosing cholangitis

ASJC Scopus subject areas

  • Surgery

Cite this

Chromosome 9p21 loss and p16 inactivation in primary sclerosing cholangitis-associated cholangiocarcinoma. / Ahrendt, Steven A.; Eisenberger, Claus F.; Yip, Lin; Rashid, Asif; Chow, John T.; Pitt, Henry A.; Sidransky, David.

In: Journal of Surgical Research, Vol. 84, No. 1, 01.06.1999, p. 88-93.

Research output: Contribution to journalArticle

Ahrendt, Steven A. ; Eisenberger, Claus F. ; Yip, Lin ; Rashid, Asif ; Chow, John T. ; Pitt, Henry A. ; Sidransky, David. / Chromosome 9p21 loss and p16 inactivation in primary sclerosing cholangitis-associated cholangiocarcinoma. In: Journal of Surgical Research. 1999 ; Vol. 84, No. 1. pp. 88-93.
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abstract = "Background. Cholangiocarcinoma is a frequent complication of primary sclerosing cholangitis and is a leading cause of mortality in patients with this disease. The tumor suppressor gene p16 is commonly inactivated in many neoplasms; however, the role of p16 in the pathogenesis of cholangiocarcinoma is unclear. Therefore, we examined the role of p16 inactivation in the pathogenesis of cholangiocarcinoma associated with primary sclerosing cholangitis. Materials and methods. Paraffin-embedded sections from 10 patients who developed cholangiocarcinoma in the setting of primary sclerosing cholangitis were examined. Chromosomal loss at 9p21 was determined using microsatellite analysis. Methylation of a CpG island in the promoter region of the p16 gene was determined using methylation-specific polymerase chain reaction. p16 inactivation was also determined using immunohistochemistry. Results. Allelic loss at chromosome 9p21 was present in 9 of 10 tumors (90{\%}). Methylation of the p16 promoter was present in 2 of the 8 tumors examined (25{\%}). Four of seven tumors (57{\%}) analyzed by immunohistochemistry demonstrated an absence of p16 nuclear staining. Conclusions. Loss of chromosome 9p21 and inactivation of the p16 tumor suppressor gene are common events in primary sclerosing cholangitis- associated cholangiocarcinoma and may play a role in the high incidence of cholangiocarcinoma in patients with primary sclerosing cholangitis.",
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N2 - Background. Cholangiocarcinoma is a frequent complication of primary sclerosing cholangitis and is a leading cause of mortality in patients with this disease. The tumor suppressor gene p16 is commonly inactivated in many neoplasms; however, the role of p16 in the pathogenesis of cholangiocarcinoma is unclear. Therefore, we examined the role of p16 inactivation in the pathogenesis of cholangiocarcinoma associated with primary sclerosing cholangitis. Materials and methods. Paraffin-embedded sections from 10 patients who developed cholangiocarcinoma in the setting of primary sclerosing cholangitis were examined. Chromosomal loss at 9p21 was determined using microsatellite analysis. Methylation of a CpG island in the promoter region of the p16 gene was determined using methylation-specific polymerase chain reaction. p16 inactivation was also determined using immunohistochemistry. Results. Allelic loss at chromosome 9p21 was present in 9 of 10 tumors (90%). Methylation of the p16 promoter was present in 2 of the 8 tumors examined (25%). Four of seven tumors (57%) analyzed by immunohistochemistry demonstrated an absence of p16 nuclear staining. Conclusions. Loss of chromosome 9p21 and inactivation of the p16 tumor suppressor gene are common events in primary sclerosing cholangitis- associated cholangiocarcinoma and may play a role in the high incidence of cholangiocarcinoma in patients with primary sclerosing cholangitis.

AB - Background. Cholangiocarcinoma is a frequent complication of primary sclerosing cholangitis and is a leading cause of mortality in patients with this disease. The tumor suppressor gene p16 is commonly inactivated in many neoplasms; however, the role of p16 in the pathogenesis of cholangiocarcinoma is unclear. Therefore, we examined the role of p16 inactivation in the pathogenesis of cholangiocarcinoma associated with primary sclerosing cholangitis. Materials and methods. Paraffin-embedded sections from 10 patients who developed cholangiocarcinoma in the setting of primary sclerosing cholangitis were examined. Chromosomal loss at 9p21 was determined using microsatellite analysis. Methylation of a CpG island in the promoter region of the p16 gene was determined using methylation-specific polymerase chain reaction. p16 inactivation was also determined using immunohistochemistry. Results. Allelic loss at chromosome 9p21 was present in 9 of 10 tumors (90%). Methylation of the p16 promoter was present in 2 of the 8 tumors examined (25%). Four of seven tumors (57%) analyzed by immunohistochemistry demonstrated an absence of p16 nuclear staining. Conclusions. Loss of chromosome 9p21 and inactivation of the p16 tumor suppressor gene are common events in primary sclerosing cholangitis- associated cholangiocarcinoma and may play a role in the high incidence of cholangiocarcinoma in patients with primary sclerosing cholangitis.

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