Originally published as JCO Early Release 10.1200/JCO.2008.17.7188 on March 9 2009

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DPC4 Gene Status of the Primary Carcinoma Correlates With Patterns of Failure in Patients With Pancreatic Cancer

From the Departments of Pathology, Surgery, and Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore MD; and the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and Department of Surgery and the Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia PA.

Corresponding author: Christine A. Iacobuzio-Donahue, MD, PhD, Johns Hopkins Medical Institutions, Department of Pathology, GI/Liver Division, 1550 Orleans St, CRBII Rm 343, Baltimore, MD 21231; e-mail: ciacobu{at}jhmi.edu.

Purpose Contrary to the extensive data accumulated regarding pancreatic carcinogenesis, the clinical and molecular features characteristic of advanced stage (stage III and IV) disease are unknown. A comprehensive study of pancreatic cancers from patients who have succumbed to their disease has the potential to greatly expand our understanding of the most lethal stage of this disease and identify novel areas for intervention.

Materials and Methods Rapid autopsies were performed on 76 patients with documented pancreatic cancer. The histologic features of end stage disease were determined and correlated to the stage at initial diagnosis, patterns of failure (locally destructive v metastatic disease) and the status of the KRAS2, TP53, and DPC4 genes.

Results At autopsy, 30% of patients died with locally destructive pancreatic cancer, and 70% died with widespread metastatic disease. These divergent patterns of failure found at autopsy (locally destructive v metastatic) were unrelated to clinical stage at initial presentation, treatment history, or histopathologic features. However, Dpc4 immunolabeling status of carcinoma tissues harvested at autopsy, a sensitive marker of DPC4 genetic status, was highly correlated with the presence of widespread metastasis but not with locally destructive tumors (P = .007).

Conclusion Pancreatic cancers are represented by distinct genetic subtypes with significantly different patterns of failure. Determinations of DPC4 status at initial diagnosis may be of value in stratifying patients into treatment regimens related to local control versus systemic therapy.

Supported by grants No. CA62924 and CA106610 from the National Institutes of Health (C.I.D.), The Joseph C. Monastra Fund for Pancreatic Cancer Research, The Jeff Zgonina Fund for Pancreatic Cancer Research, The George Rubis Endowment for Pancreatic Cancer Research, The Michael Rolfe Pancreatic Cancer Foundation, and the Sigma Beta Sorority.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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