{"entity":{"id":"paper-iacobuzio-donahue-dpc4-failure-pattern-autopsy-jco-2009","kind":"paper","name":"DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer","aka":[],"tldr":"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).","asOf":"2026-09-24","links":[{"label":"Iacobuzio-Donahue et al., J Clin Oncol 2009: DPC4 (SMAD4) status and pattern of failure in 76 rapid autopsies","url":"https://doi.org/10.1200/JCO.2008.17.7188"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19273710/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac","locally-advanced-pdac"],"sections":[],"technologies":[],"targets":["smad4","kras","tp53"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["tgf-beta","metastatic-cascade"],"terms":["ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2009,"doi":"10.1200/JCO.2008.17.7188","pmid":"19273710","authors":"Iacobuzio-Donahue CA, Fu B, Yachida S, et al.","paperType":"observational","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."],"whatItMeans":"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)."],"changedPractice":false,"participants":76},"route":"/key-papers/paper-iacobuzio-donahue-dpc4-failure-pattern-autopsy-jco-2009/","neighbours":{"cancer":[{"id":"locally-advanced-pdac","kind":"cancer","name":"Locally advanced unresectable pancreatic ductal adenocarcinoma","route":"/cancers/locally-advanced-pdac/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"target":[{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"smad4","kind":"target","name":"SMAD4","route":"/targets/smad4/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"institution":[{"id":"johns-hopkins","kind":"institution","name":"Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center","route":"/institutions/johns-hopkins/"}],"pathway":[{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"},{"id":"metastatic-cascade","kind":"pathway","name":"The metastatic cascade","route":"/pathways/metastatic-cascade/"}],"term":[{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}