# DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer

Source: https://onco.cc/key-papers/paper-iacobuzio-donahue-dpc4-failure-pattern-autopsy-jco-2009/  
OnCo record `paper-iacobuzio-donahue-dpc4-failure-pattern-autopsy-jco-2009` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Autopsies of 76 people who died of pancreatic cancer showed two ways the disease kills: 70% died with cancer spread through the body and 30% with a locally destructive tumour, and whether the SMAD4 (DPC4) gene was intact predicted which.

## Summary

Rapid autopsies were performed on 76 patients with documented pancreatic cancer; the histology of end-stage disease was correlated with stage at diagnosis, pattern of failure (locally destructive versus metastatic) and the status of KRAS2, TP53 and DPC4. At autopsy 30% had died with locally destructive cancer and 70% with widespread metastases; the divergent patterns were unrelated to clinical stage at presentation, treatment history or histopathology. Dpc4 immunolabelling status of carcinoma tissue, a sensitive marker of DPC4 genetic status, was highly correlated with widespread metastasis but not with locally destructive tumours (P = .007).

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Journal of Clinical Oncology
- Year: 2009
- DOI: 10.1200/JCO.2008.17.7188
- Authors: Iacobuzio-Donahue CA, Fu B, Yachida S, et al.
- Findings: 30% died with locally destructive disease, 70% with widespread metastases.; Dpc4 (SMAD4) loss correlated with the metastatic pattern (P = .007) and intact Dpc4 with local destruction.
- What it means: SMAD4 status is the clearest published molecular marker of how pancreatic cancer will behave: intact argues for local control, lost argues for systemic therapy.
- Caveats: Autopsy series at one institution; treatment predates modern combination chemotherapy.; SMAD4 was not prognostic for survival after resection in later work (Qian 2018).

## Sources

- Iacobuzio-Donahue et al., J Clin Oncol 2009: DPC4 (SMAD4) status and pattern of failure in 76 rapid autopsies: https://doi.org/10.1200/JCO.2008.17.7188
- PubMed: https://pubmed.ncbi.nlm.nih.gov/19273710/

## Connected records

- cancers: [Locally advanced unresectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/locally-advanced-pdac/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- targets: [KRAS](https://onco.cc/targets/kras/), [SMAD4](https://onco.cc/targets/smad4/), [TP53](https://onco.cc/targets/tp53/)
- institutions: [Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center](https://onco.cc/institutions/johns-hopkins/)
- pathways: [TGF-β signalling](https://onco.cc/pathways/tgf-beta/), [The metastatic cascade](https://onco.cc/pathways/metastatic-cascade/)
- terms: [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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