Topic Completed: 1 June 2005

Minor changes: 2 June 2020

Copyright: 2003-2019,, Inc.

PubMed Search: DPC4[title]

Nat Pernick, M.D.
Page views in 2019: 3,605
Page views in 2020 to date: 2,542
Cite this page: Pernick N. DPC4. website. Accessed August 4th, 2020.
Definition / general
  • Also called MADH4, SMAD4
  • Tumor suppressor gene on 18q21.1 that mediates the downstream effect of the TGF-beta superfamily signaling, resulting in growth inhibition and apoptosis
  • Inactivation relatively specific for pancreatic adenocarcinoma, but only 55% sensitive in usual pancreatic ductal adenocarcinomas and 34% sensitive in ampullary carcinoma; may not be inactivated in IPMN associated colloid carcinoma (Mod Pathol 2005;18:1034)
  • Mutations in 20% of colorectal carcinomas
  • Staining is primarily nuclear with some cytoplasmic, and is normally present in benign tissues; loss of nuclear staining is considered an abnormal or "positive" result, with adjacent pancreatic stroma retaining expression
Uses by pathologists
  • Loss of expression specific for pancreatic malignancy (in-situ or invasive) vs. benign process, particularly helpful in biopsies (Am J Clin Pathol 2001;116:831)
  • Expression in PanIN may predict its expression in a subsequent invasive ductal adenocarcinoma, and distinguish recurrent or persistent adenocarcinoma from a second primary adenocarcinoma (Hum Pathol 2001;32:638)
Positive staining - normal
  • Normal pancreatic ducts, islets and acini
Positive staining - tumors
  • Carcinoma in situ in mucinous cystic neoplasms
Negative staining
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