Author: Nat Pernick, M.D. (see Authors page)

Revised: 8 December 2015, last major update June 2005

Copyright: (c) 2003-2015,, Inc.

PubMed Search: DPC4[title]

Cite this page: DPC4. website. Accessed July 23rd, 2018.
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 cytoplasmic; adjacent pancreatic stroma also stains in benign and malignant mucinous cystic neoplasms
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
Microscopic (histologic) images

Images hosted on

DPC4 staining in invasive ampullary carcinoma and high grade dysplasia

Staining in pancreatic lesions - PANIN, invasive disease, IPMN