title: Detection of early-stage pancreatic adenocarcinoma.
abstract: BACKGROUND
  Pancreatic adenocarcinoma is an almost universally lethal disease, in large part, due to our inability to detect early-stage disease. Monoclonal antibody PAM4 is reactive with a unique biomarker expressed by >85% of pancreatic adenocarcinomas. In this report, we examined the ability of a PAM4-based immunoassay to detect early-stage disease.
  
  
  METHODS
  The PAM4-based immunoassay was used to quantitate antigen in the serum of healthy volunteers (n = 19), patients with known pancreatic adenocarcinoma (n = 68), and patients with a primary diagnosis of chronic pancreatitis (n = 29).
  
  
  RESULTS
  Sensitivity for detection of pancreatic adenocarcinoma was 82%, with a false-positive rate of 5% for healthy controls. Patients with advanced disease had significantly higher antigen levels than those with early-stage disease (P < 0.01), with a diagnostic sensitivity of 91%, 86%, and 62% for stage 3/stage 4 advanced disease, stage 2, and stage 1, respectively. We also evaluated chronic pancreatitis sera, finding 38% positive for antigen; however, this was discordant with immunohistochemical findings that suggest the PAM4 antigen is not produced by inflamed pancreatic tissue. Furthermore, several of the serum-positive pancreatitis patients, for whom tissue specimens were available for pathologic interpretation, had evidence of neoplastic precursor lesions.
  
  
  CONCLUSIONS
  These results suggest the use of the PAM4 serum assay to detect early-stage pancreatic adenocarcinoma and that positive levels of PAM4 antigen are not derived from inflamed pancreatic tissues but rather may provide evidence of subclinical pancreatic neoplasia. EFFECT: The ability to detect pancreatic adenocarcinoma at an early stage could provide for early therapeutic intervention with potentially improved patient outcomes.
authors.affiliation: Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA. dvgold@gscancer.org
authors.forename: David V
authors.initials: DV
authors.lastname: Gold
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
authors.forename: David E
authors.initials: DE
authors.lastname: Modrak
authors.forename: Guy
authors.initials: G
authors.lastname: Newsome
authors.forename: Mengling
authors.initials: M
authors.lastname: Liu
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Shi
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis*; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012680:Sensitivity and Specificity
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C550275:PAM4 protein, human
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