Genomic Identification of Biomarkers of Behavior of Pancreatic Endocrine Tumors
J Bauersfeld, DG Thomas, R Kuick, M Vinco, D Sanders, TJ Giordano. University of Michigan, Ann Arbor, MI
Background: Endocrine tumors of the pancreas are difficult to classify into benign and malignant categories, and as such are often diagnosed as pancreatic endocrine tumors (PETs). The recent WHO classification has improved this situation, but there is still a need for additional molecular biomarkers to provide independent assessment of the risk of malignant behavior.
Design: To identify potential biomarkers of malignant behavior, genome-wide transcriptional profiles were generated for a cohort of 45 PETs using commercially available DNA microarrays. PETs analyzed represented sporadic and syndromic (MEN-1) forms, and primary metastasizing and non-metastasizing tumors, and metastatic tumors.
Results: Using F-tests and selection criteria of p<0.01 and fold change > 1.5 in either direction, comparison of 8 PETs with proven metastases (PET-M) to 6 PETs without metastases (PET-N) yielded 255 unique genes whose expression was increased in the PEN-M group and 142 unique genes whose expression was decreased in the PEN-M group. Differentially expressed genes included genes related to tumor invasion and metastasis, as well as other biological processes. Preliminary results from immunohistochemical and AQUA-based validation for several of these biomarkers using tissue arrays containing an independent set of PETs are promising and ongoing.
Conclusions: Genomic investigation of pancreatic endocrine tumors will yield novel biomarkers that will permit a more refined assessment of their risk of malignant behavior. Application of these biomarkers to pathology practice will improve the management of patients with PETs.
Category: Special Category for 2009 - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 242, Tuesday Morning