to distinguish benign reactive glands from infiltrating ductal adenocarcinoma of the pancreas
The gene expression patterns of 24 surgically resected primary infiltrating ductal adenocarcinomas of the pancreas
were compared with 18 non-neoplastic samples using the Affymetrix U133 Plus 2.0 Arrays and the Gene Logic GeneExpress Software System. Gene fragments from 4 genes (annexin A8, claudin 18, CXCL5, and S100 A2
) were selected from the fragments found to be highly expressed in infiltrating adenocarcinomas when compared with normal tissues. The protein expression of these genes was examined using immunohistochemical labeling of tissue microarrays.
18 labeled infiltrating carcinomas in a membranous pattern. When compared with normal and reactive ducts, claudin
18 was overexpressed, at least focally, in 159 of 166 evaluable carcinomas (96%). Strong and diffuse claudin
18 overexpression was most often seen in well-differentiated carcinomas (P
18 was overexpressed in 51 of 52 cases (98%) of pancreatic intraepithelial neoplasia
A8 was at least focally overexpressed in 149 of 154 evaluable infiltrating carcinomas (97%). S100 A2 was at least focally overexpressed in 118 of 154 evaluable infiltrating carcinomas (77%). Non-neoplastic glands also frequently expressed S100 A2 diminishing its potential diagnostic utility. Immunolabeling with antibodies directed against CXCL5 did not reveal any significant differences in protein expression between infiltrating adenocarcinomas and normal pancreatic ducts.
18 and annexin
A8 are frequently highly overexpressed in infiltrating ductal adenocarcinomas when compared with 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.