title: New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8.
abstract: BACKGROUND
  New markers to distinguish benign reactive glands from infiltrating ductal adenocarcinoma of the pancreas are needed.
  
  
  METHODS
  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.
  
  
  RESULTS
  Claudin 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=0.02). Claudin 18 was overexpressed in 51 of 52 cases (98%) of pancreatic intraepithelial neoplasia. Annexin 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.
  
  
  CONCLUSIONS
  Claudin 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.
authors.affiliation: The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231-2410, USA.
authors.forename: Zarir E
authors.initials: ZE
authors.lastname: Karanjawala
authors.forename: Peter B
authors.initials: PB
authors.lastname: Illei
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Infante
authors.forename: Kathleen
authors.initials: K
authors.lastname: Murphy
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.forename: Richard
authors.initials: R
authors.lastname: Schulick
authors.forename: Jordan
authors.initials: J
authors.lastname: Winter
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
mesh_terms: D000368:Aged; D017302:Annexins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D057167:Claudins; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D015996:Survival Rate
chemical_list: D017302:Annexins; D014408:Biomarkers, Tumor; C486683:CLDN18 protein, human; D057167:Claudins; D008565:Membrane Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm