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Telomeres are shortened in acinar-to-ductal metaplasia lesions associated with pancreatic intraepithelial neoplasia but not in isolated acinar-to-ductal metaplasias.

Publication ,  Journal Article
Hong, S-M; Heaphy, CM; Shi, C; Eo, S-H; Cho, H; Meeker, AK; Eshleman, JR; Hruban, RH; Goggins, M
Published in: Mod Pathol
February 2011

Telomeres protect against chromosomal breakage, fusion, and interchromosome bridges during cell division. Shortened telomeres have been observed in the lowest grade of pancreatic intraepithelial neoplasia (PanIN). Genetically engineered mouse models of pancreatic neoplasia develop acinar-to-ductal metaplasia prior to the development of PanIN, suggesting that acinar-to-ductal metaplasias can be an early precursor lesion to pancreatic cancer. Some human PanINs are associated with acinar-to-ductal metaplasias, and it has been suggested that these acinar-to-ductal metaplasias arise as a consequence of growth of adjacent PanINs. As the earliest known genetic lesions of PanINs is shortened telomeres, we compared the telomere lengths of acinar-to-ductal metaplasia lesions, PanINs, and adjacent normal cells of human pancreata to determine whether acinar-to-ductal metaplasias could be precursors to PanIN. We used quantitative fluorescent in situ hybridization to measure the telomere length of cells from pancreatic lesions and adjacent normal pancreata from 22 patients, including 20 isolated acinar-to-ductal metaplasias, 13 PanINs associated with acinar-to-ductal metaplasias, and 12 PanINs. Normalized mean telomere fluorescence was significantly different among the cell types analyzed; 12.6 ± 10.2 units in normal acinar cells, 10.2 ± 6.4 in ductal cells, 8.4 ± 5.9 in fibroblasts, 9.4 ± 7.3 in isolated acinar-to-ductal metaplasias, 4.1 ± 2.9 in PanIN-associated acinar-to-ductal metaplasias, and 1.6 ± 1.9 in PanINs, respectively (P<0.001, ANOVA with randomized block design). Telomeres were significantly shorter in PanIN-associated acinar-to-ductal metaplasias (P<0.05, post hoc Duncan test) and in PanINs (P<0.05), than in normal cells, or isolated acinar-to-ductal metaplasias. Thus, shortened telomeres are found in PanIN-associated acinar-to-ductal metaplasias, but not in isolated acinar-to-ductal metaplasia lesions. These results indicate that isolated acinar-to-ductal metaplasias are not a precursor to PanIN, and support the hypothesis that PanIN-associated acinar-to-ductal metaplasias arise secondary to PanIN lesions.

Duke Scholars

Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

February 2011

Volume

24

Issue

2

Start / End Page

256 / 266

Location

United States

Related Subject Headings

  • Telomere
  • Pathology
  • Pancreatic Neoplasms
  • Pancreas
  • Metaplasia
  • In Situ Hybridization, Fluorescence
  • Humans
  • Carcinoma in Situ
  • Analysis of Variance
  • 3202 Clinical sciences
 

Citation

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Hong, S.-M., Heaphy, C. M., Shi, C., Eo, S.-H., Cho, H., Meeker, A. K., … Goggins, M. (2011). Telomeres are shortened in acinar-to-ductal metaplasia lesions associated with pancreatic intraepithelial neoplasia but not in isolated acinar-to-ductal metaplasias. Mod Pathol, 24(2), 256–266. https://doi.org/10.1038/modpathol.2010.181
Hong, Seung-Mo, Christopher M. Heaphy, Chanjuan Shi, Soo-Heang Eo, HyungJun Cho, Alan K. Meeker, James R. Eshleman, Ralph H. Hruban, and Michael Goggins. “Telomeres are shortened in acinar-to-ductal metaplasia lesions associated with pancreatic intraepithelial neoplasia but not in isolated acinar-to-ductal metaplasias.Mod Pathol 24, no. 2 (February 2011): 256–66. https://doi.org/10.1038/modpathol.2010.181.
Hong, Seung-Mo, et al. “Telomeres are shortened in acinar-to-ductal metaplasia lesions associated with pancreatic intraepithelial neoplasia but not in isolated acinar-to-ductal metaplasias.Mod Pathol, vol. 24, no. 2, Feb. 2011, pp. 256–66. Pubmed, doi:10.1038/modpathol.2010.181.
Hong S-M, Heaphy CM, Shi C, Eo S-H, Cho H, Meeker AK, Eshleman JR, Hruban RH, Goggins M. Telomeres are shortened in acinar-to-ductal metaplasia lesions associated with pancreatic intraepithelial neoplasia but not in isolated acinar-to-ductal metaplasias. Mod Pathol. 2011 Feb;24(2):256–266.

Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

February 2011

Volume

24

Issue

2

Start / End Page

256 / 266

Location

United States

Related Subject Headings

  • Telomere
  • Pathology
  • Pancreatic Neoplasms
  • Pancreas
  • Metaplasia
  • In Situ Hybridization, Fluorescence
  • Humans
  • Carcinoma in Situ
  • Analysis of Variance
  • 3202 Clinical sciences