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[1298] New Markers of Pancreatic Cancer Identified through Differential Gene Expression Analyses: Claudin 18 and Annexin A8

ZE Karanjawala, PB Illei, R Ashfaq, J Infante, K Murphy, A Maitra, M Goggins, RH Hruban. The Johns Hopkins Medical Institutions, Baltimore, MD; University of Texas Southwestern Medical Center, Dallas, TX

Background: New markers to distinguish reactive glands from infiltrating carcinoma of the pancreas are needed.
Design: Gene expression patterns of 24 surgically resected primary pancreatic adenocarcinomas (CA) were compared to 18 non-neoplastic samples (NL)(14 duodenal mucosa and 4 chronic pancreatitis) using the Affymetrix U133-plus chips and the GeneExpress system (Gene Logic Inc.). Gene fragments from four genes (Annexin A8[present in 92% of CA, 11% of NL; mean intensity 393 in CA, 79 in NL], Claudin 18[present in 100% of CA, 6% of NL; mean intensity 743 in CA, 19 in NL], CXCL5[present in 100% of CA, 39% of NL; mean intensity 1096 in CA, 52 in NL]and S100 A2[present in 71% of CA, 11% of NL; mean intensity 829 in CA, 27 in NL]) were selected from the fragments highly expressed in CA. Protein expression was examined by immunohistochemical labeling of TMAs.
Results: Claudin 18 labeled carcinomas in a membranous pattern, consistent with its role in cellular adhesion. When compared to normal and reactive ducts, Claudin 18 was overexpressed, at least focally, in 159 of 165 evaluable carcinomas (96%). Of these 159 cancers, 52% expressed Claudin 18 strongly and diffusely. Strong and diffuse claudin 18 overexpression was most often seen in well-differentiated carcinomas, while more poorly differentiated carcinomas often labeled focally or did not label. Annexin A8 is a member of a family of proteins that are calcium- and lipid-binding proteins that have proposed roles in membrane structure and transport. Annexin A8 was at least focally overexpressed in 149 of 154 evaluable carcinomas (97%). Of these 149 cancers, 69% expressed Annexin A8 strongly and diffusely. S100 A2, a calcium binding protein, was at least focally overexpressed in 118 of 154 evaluable carcinomas (77%). Of these 118 cancers, 34% demonstrated strong and diffuse overexpression of S100 A2. Non-neoplastic glands also frequently expressed S100 A2 diminishing its potential diagnostic utility. No significant differences in CXCL5 expression were observed between adenocarcinomas and normal ducts.
Conclusions: Claudin 18 and Annexin A8 are frequently overexpressed in infiltrating ductal adenocarcinomas when compared to normal reactive ducts, suggesting a role for these molecules in pancreatic ductal adenocarcinomas. Furthermore, these may serve as diagnostic markers, as screening tests and as therapeutic targets.
Category: Liver & Pancreas

Monday, March 26, 2007

Poster # 183, Monday Morning