TY - JOUR
T1 - DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer
AU - Lacobuzio-Donahue, Christine A.
AU - Fu, Baojin
AU - Yachida, Shinichi
AU - Luo, Mingde
AU - Abe, Hisashi
AU - Henderson, Clark M.
AU - Vilardell, Felip
AU - Wang, Zheng
AU - Keller, Jesse W.
AU - Banerjee, Priya
AU - Herman, Joseph M.
AU - Cameron, John L.
AU - Yeo, Charles J.
AU - Halushka, Marc K.
AU - Eshleman, James R.
AU - Raben, Marian
AU - Klein, Alison P.
AU - Hruban, Ralph H.
AU - Hidalgo, Manuel
AU - Laheru, Daniel
PY - 2009/4/10
Y1 - 2009/4/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=62249176551&partnerID=8YFLogxK
U2 - 10.1200/JCO.2008.17.7188
DO - 10.1200/JCO.2008.17.7188
M3 - Article
C2 - 19273710
AN - SCOPUS:62249176551
SN - 0732-183X
VL - 27
SP - 1806
EP - 1813
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -