<i>DPC4</i> Gene Status of the Primary Carcinoma Correlates With Patterns of Failure in Patients With Pancreatic Cancer

TLDR

Advanced stage pancreatic cancer (stage III/IV) has poorly characterized clinical and molecular features. The study aims to analyze pancreatic cancers from patients who died to better understand the lethal stage and identify new intervention targets. The authors performed rapid autopsies on 76 patients, assessed histologic features, and correlated them with initial stage, failure patterns, and KRAS2, TP53, and DPC4 gene status. Autopsy data revealed that 30 % of patients had locally destructive tumors while 70 % had metastatic disease, with DPC4 loss strongly associated with metastasis but not local destruction, indicating distinct genetic subtypes that could guide treatment stratification.

Abstract

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.