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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.
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).
SMAD4 status is the clearest published molecular marker of how pancreatic cancer will behave: intact argues for local control, lost argues for systemic therapy.
Shares SMAD4, Immunohistochemistry (IHC), Locally advanced unresectable pancreatic ductal adenocarcinoma, Journal of Clinical Oncology.
Shares SMAD4, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, TP53, KRAS.
Shares SMAD4, TP53, KRAS, Pancreatic ductal adenocarcinoma.
Shares The metastatic cascade, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma.
Shares SMAD4, TGF-β signalling, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, Pancreatic ductal adenocarcinoma.
Shares Locally advanced unresectable pancreatic ductal adenocarcinoma, KRAS, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma.
Shares SMAD4, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, TP53, KRAS.
Shares SMAD4, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, TP53, KRAS.