Skip to main content

p16 Inactivation in pancreatic intraepithelial neoplasias (PanINs) arising in patients with chronic pancreatitis.

Publication ,  Journal Article
Rosty, C; Geradts, J; Sato, N; Wilentz, RE; Roberts, H; Sohn, T; Cameron, JL; Yeo, CJ; Hruban, RH; Goggins, M
Published in: Am J Surg Pathol
December 2003

Patients with long-standing chronic pancreatitis are thought to be at increased risk of developing pancreatic ductal adenocarcinoma, but the mechanism for this increased risk is unknown. Since increasing evidence supports the notion that infiltrating pancreatic ductal adenocarcinomas arise from pancreatic intraepithelial lesions (PanINs), we sought to determine if patients with chronic pancreatitis harbor PanINs with alterations in tumor suppressor genes that are associated with infiltrating pancreatic ductal adenocarcinoma. We identified 122 patients with a diagnosis of chronic pancreatitis and 29 patients with a well-differentiated pancreatic endocrine tumor that underwent pancreatic surgery at the Johns Hopkins Hospital from 1985 to 1999. PanINs from each resection specimen were identified, graded, counted, and correlated with smoking and alcohol history. The expression patterns of p16 and Smad4 were determined in a subset of PanINs by immunohistochemistry, and the pattern of labeling compared with that seen in PanINs associated with infiltrating adenocarcinoma of the pancreas as identified in prior studies, and to PanINs associated with pancreatic endocrine tumor. Duct lesions were present in 80 of the 122 pancreata with chronic pancreatitis (66%). Of 405 duct lesions identified in the chronic pancreatitis group, 7.6% were reactive changes, 65.5% were PanIN-1A, 18% were PanIN-1B, 7.4% were PanIN-2, and 1.5% were PanIN-3. Within the pancreatic endocrine tumor group, 22 PanINs were identified: 15 PanIN-1A, 4 PanIN-1B, and 3 PanIN-2. There were significantly fewer high-grade PanINs in the pancreata with chronic pancreatitis than in pancreata with pancreatic adenocarcinoma (P < 0.0001). Within the chronic pancreatitis group, the 80 patients with PanINs were significantly older than the 42 patients without PanINs (mean age 57.0 +/- 14.1 years vs. 50.9 +/- 14.7 years, P = 0.01). Smoking history was not associated with PanIN prevalence or grade, but patients who reported a history of excessive alcohol consumption had fewer PanINs (25 of 44 harbored PanINs, 57%) than those who did not (54 of 74, 73%, P = 0.07). In the chronic pancreatitis group, 0% of PanIN-1A, 11% of the PanIN-1B, 16% of the PanIN-2, and 40% of the PanIN-3 lesions showed loss of p16 expression, whereas all of the PanINs from patients with an pancreatic endocrine tumor retained p16 expression. All of the PanINs analyzed from patients with chronic pancreatitis retained normal Smad4 expression. We conclude that a significant minority of PanINs arising in patients with chronic pancreatitis show loss of p16 expression. This alteration, common to pancreatic cancer-associated PanINs, may contribute to the predisposition of patients with chronic pancreatitis to develop pancreatic ductal adenocarcinoma.

Duke Scholars

Published In

Am J Surg Pathol

DOI

ISSN

0147-5185

Publication Date

December 2003

Volume

27

Issue

12

Start / End Page

1495 / 1501

Location

United States

Related Subject Headings

  • Trans-Activators
  • Smad4 Protein
  • Risk Factors
  • Pathology
  • Pancreatitis
  • Pancreatic Neoplasms
  • Middle Aged
  • Male
  • Immunohistochemistry
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rosty, C., Geradts, J., Sato, N., Wilentz, R. E., Roberts, H., Sohn, T., … Goggins, M. (2003). p16 Inactivation in pancreatic intraepithelial neoplasias (PanINs) arising in patients with chronic pancreatitis. Am J Surg Pathol, 27(12), 1495–1501. https://doi.org/10.1097/00000478-200312000-00001
Rosty, Christophe, Joseph Geradts, Norihiro Sato, Robb E. Wilentz, Helen Roberts, Taylor Sohn, John L. Cameron, Charles J. Yeo, Ralph H. Hruban, and Michael Goggins. “p16 Inactivation in pancreatic intraepithelial neoplasias (PanINs) arising in patients with chronic pancreatitis.Am J Surg Pathol 27, no. 12 (December 2003): 1495–1501. https://doi.org/10.1097/00000478-200312000-00001.
Rosty C, Geradts J, Sato N, Wilentz RE, Roberts H, Sohn T, et al. p16 Inactivation in pancreatic intraepithelial neoplasias (PanINs) arising in patients with chronic pancreatitis. Am J Surg Pathol. 2003 Dec;27(12):1495–501.
Rosty, Christophe, et al. “p16 Inactivation in pancreatic intraepithelial neoplasias (PanINs) arising in patients with chronic pancreatitis.Am J Surg Pathol, vol. 27, no. 12, Dec. 2003, pp. 1495–501. Pubmed, doi:10.1097/00000478-200312000-00001.
Rosty C, Geradts J, Sato N, Wilentz RE, Roberts H, Sohn T, Cameron JL, Yeo CJ, Hruban RH, Goggins M. p16 Inactivation in pancreatic intraepithelial neoplasias (PanINs) arising in patients with chronic pancreatitis. Am J Surg Pathol. 2003 Dec;27(12):1495–1501.

Published In

Am J Surg Pathol

DOI

ISSN

0147-5185

Publication Date

December 2003

Volume

27

Issue

12

Start / End Page

1495 / 1501

Location

United States

Related Subject Headings

  • Trans-Activators
  • Smad4 Protein
  • Risk Factors
  • Pathology
  • Pancreatitis
  • Pancreatic Neoplasms
  • Middle Aged
  • Male
  • Immunohistochemistry
  • Humans