title: Prospective markers for early diagnosis and prognosis of sporadic pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  Sporadic pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. No proven screening strategies are available and frequent cross-sectional imaging studies (CT/MRI) are impractical even in patients thought to be at higher risk than the general population. Few PDA biomarkers have been studied prospectively for screening. Here, we prospectively evaluated the Adnab-9 monoclonal antibody in stool, pancreaticobiliary secretions, and tissue for screening and prognostic value in sporadic PDA. We also evaluated the prognostic value of characterized early biomarkers in pancreaticobiliary secretions.
  
  
  METHODS
  Adnab-9 diagnostic ability was tested in stool in 249 and 1,132 patients from China and the US, respectively. Immunohistochemistry was performed in 22 tissue samples with Adnab-9 antibody and anti-Defensin 5, a constituent of Paneth cells. Pancreatobiliary secretions were collected from 12 PDA patients and 9 controls. The enriched PCR method was performed to detect K-ras mutations. ELISA was performed with Adnab-9, anti-Her-2/neu, and monoclonal antibody D4 (anti-Reg I).
  
  
  RESULTS
  Adnab-9 alone was diagnostic and prognostic when measured in pancreatic secretions, feces, and tissues of PDA patients compared to controls (p < 0.05). Significantly, Adnab-9 fecal binding can precede the clinical diagnosis by 2.3 years, potentially allowing earlier clinical intervention. In pancreatic secretions, a combination of K-ras and Her-2/neu when appropriately standardized can be diagnostic in 75 % of PDA.
  
  
  CONCLUSIONS
  Our study suggests that Adnab-9 may be an effective marker for diagnosis and prognosis of PDA. Adnab-9 may be reflective of the presence of Paneth cells confirmed by Defensin-5 staining. These cells may modulate the biological activity of the cancer and confer a better prognosis.
authors.affiliation: Gastroenterology Section, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104, USA. Martin.Tobi@va.gov
authors.forename: Martin
authors.initials: M
authors.lastname: Tobi
authors.forename: Mijin
authors.initials: M
authors.lastname: Kim
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Weinstein
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Rambus
authors.forename: James
authors.initials: J
authors.lastname: Hatfield
authors.forename: N Volkan
authors.initials: NV
authors.lastname: Adsay
authors.forename: Edi
authors.initials: E
authors.lastname: Levi
authors.forename: Douglas
authors.initials: D
authors.lastname: Evans
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lawson
authors.forename: Suzanne
authors.initials: S
authors.lastname: Fligiel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001826:Body Fluids / Q000737:chemistry; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D000911:Antibodies, Monoclonal
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C516879:Adnab-9; D000911:Antibodies, Monoclonal; C508053:ERBB2 protein, human