Biomarker Profiles Associated with Metastatic Pancreatic Cancer
Y Naito, CA Iacobuzio-Donahue. The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, MD; The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD
Background: We recently reported that pancreatic duct adenocarcinomas are represented by two distinct subtypes, locally destructive pancreatic cancer and widely metastatic pancreatic cancer, based on their significantly different patterns of failure and metastatic burden encountered at autopsy (Iacobuzio-Donahue et al. JCO 2009). These divergent patterns of failure found at autopsy were unrelated to clinical stage at initial presentation, treatment history, or histopathologic features. Our current goal is to characterize the biomarker profiles characteristic of these two biological subtypes of pancreatic cancer using a high-throughput immunohistochemical approach.
Design: Primary and metastatic cancer tissues from 36 patients who underwent a rapid autopsy in association with the Gastrointestinal Cancer Rapid Medical Donation Program were used to construct a tissue microarray (TMA) containing 208 cores (4 cores per patient). IHC was used to evaluate the expression of 30 biomarkers related to the cytoskeleton, apomucins, tumor antigens, stroma, adhesion, proliferation, cell cycle, Wnt signaling, TGF-beta signaling, Kras signaling, and PTEN signaling. Labeling patterns were correlated to patterns of failure, primary versus metastatic site, and metastatic burden.
Results: At diagnosis, the majority of carcinomas (21/36, 58%) were located in the pancreatic head and the average tumor diameter was 5.6±2.8cm. The overall survival for all patients was 7.5±23.2 months. At autopsy, 13 patients had locally destructive pancreatic cancer and 23 had widely metastatic pancreatic cancer. There were no significant differences in labeling for any marker between matched primary and metastatic samples. However, distinct differences in labeling patterns were noted in association with increasing metastatic burden, in that labeling for vimentin, mesothelin, phospho-MAPK and nuclear beta-catenin was more pronounced in widely metastatic pancreatic cancers, whereas, labeling for DPC4 and cyclin D1 were lost in these same cancers relative to locally destructive pancreatic cancers.
Conclusions: A limited panel of biomarkers may have value in classifying pancreatic cancers based on their most likely pattern of disease progression. These markers also highlight avenues for investigation into the fundamental features associated with metastatic spread.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 215, Tuesday Afternoon