Telomere length variation in biliary tract metaplasia, dysplasia, and carcinoma

Donna E. Hansel, Alan Keith Meeker, Jessica Hicks, Angelo Michael Demarzo, Keith D. Lillemoe, Richard Schulick, Ralph H Hruban, Anirban Maitra, Pedram Argani

Research output: Contribution to journalArticle

Abstract

Biliary tract carcinoma, including carcinoma of the gallbladder, intrahepatic bile ducts (cholangiocarcinoma), and extrahepatic bile ducts, affects 7500 people in the United States annually, and has an overall 32% 5-year survival rate for disease limited to the mucosa, and a dismal 10% 5-year survival for more advanced disease. The identification of factors involved in the pathogenesis and progression of biliary tract carcinoma is critical for devising effective methods of screening and treatment. Recent evidence suggests that reduction of the length of telomeres, which normally help maintain chromosomal stability, may promote the development and progression of a variety of carcinomas. Using a novel, recently validated telomere fluorescence in situ hybridization method, we examined telomere length in normal and inflamed gallbladder epithelium, metaplasia and dysplasia of the gallbladder, and biliary tract carcinoma to determine whether telomere shortening is associated with neoplastic progression in the biliary tract. Although normal and inflamed gallbladder epithelium demonstrated uniform normal telomere lengths, over half of all metaplastic lesions demonstrated shortened telomeres, supporting prior evidence that metaplastic lesions of the gallbladder are pre-neoplastic. Dysplastic epithelium and invasive carcinomas demonstrated almost universally abnormally short telomeres, indicating that telomere shortening occurs at an early, preinvasive stage of cancer development. In addition, invasive adenocarcinoma of the biliary tract frequently demonstrated intratumoral heterogeneity of telomere lengths. We conclude that telomere shortening is a consistent and early finding in the development of biliary tract carcinoma.

Original languageEnglish (US)
Pages (from-to)772-779
Number of pages8
JournalModern Pathology
Volume19
Issue number6
DOIs
StatePublished - Jun 2006

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Telomere
Metaplasia
Biliary Tract
Telomere Shortening
Gallbladder
Carcinoma
Epithelium
Intrahepatic Bile Ducts
Extrahepatic Bile Ducts
Chromosomal Instability
Cholangiocarcinoma
Fluorescence In Situ Hybridization
Mucous Membrane
Adenocarcinoma
Neoplasms

Keywords

  • Bile duct
  • Carcinoma
  • Dysplasia
  • Gallbladder
  • Metaplasia
  • Telomere

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Telomere length variation in biliary tract metaplasia, dysplasia, and carcinoma. / Hansel, Donna E.; Meeker, Alan Keith; Hicks, Jessica; Demarzo, Angelo Michael; Lillemoe, Keith D.; Schulick, Richard; Hruban, Ralph H; Maitra, Anirban; Argani, Pedram.

In: Modern Pathology, Vol. 19, No. 6, 06.2006, p. 772-779.

Research output: Contribution to journalArticle

Hansel, Donna E. ; Meeker, Alan Keith ; Hicks, Jessica ; Demarzo, Angelo Michael ; Lillemoe, Keith D. ; Schulick, Richard ; Hruban, Ralph H ; Maitra, Anirban ; Argani, Pedram. / Telomere length variation in biliary tract metaplasia, dysplasia, and carcinoma. In: Modern Pathology. 2006 ; Vol. 19, No. 6. pp. 772-779.
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