Table of Contents
Definition / general | Interpretation | Uses by pathologists | Positive staining - normal | Positive staining - tumors | Negative staining | Microscopic (histologic) imagesCite this page: DPC4. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsdpc4.html. Accessed July 12th, 2017.
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
Interpretation
- 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
- Invasive mucinous cystic neoplasms (Am J Surg Pathol 2000;24:1544), some in-situ and invasive pancreatic adenocarcinomas


