Original Article

Digestive Diseases and Sciences

, Volume 58, Issue 3, pp 744-750

Prospective Markers for Early Diagnosis and Prognosis of Sporadic Pancreatic Ductal Adenocarcinoma

  • Martin TobiAffiliated withGastroenterology Section, Philadelphia Veterans Affairs Medical CenterDivision of Gastroenterology, Department of Medicine, University of Pennsylvania School of MedicineDepartment of Medicine and Pathology, John D. Dingell Veterans Affairs Medical Center, Wayne State University School of Medicine Email author 
  • , Mijin KimAffiliated withDivision of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine
  • , Douglas H. WeinsteinAffiliated withGastroenterology Section, Philadelphia Veterans Affairs Medical Center
  • , Mary Ann RambusAffiliated withDepartment of Medicine and Pathology, John D. Dingell Veterans Affairs Medical Center, Wayne State University School of Medicine
  • , James HatfieldAffiliated withDepartment of Medicine and Pathology, John D. Dingell Veterans Affairs Medical Center, Wayne State University School of Medicine
  • , N. Volkan AdsayAffiliated withDepartment of Medicine and Pathology, John D. Dingell Veterans Affairs Medical Center, Wayne State University School of Medicine
  • , Edi LeviAffiliated withDepartment of Medicine and Pathology, John D. Dingell Veterans Affairs Medical Center, Wayne State University School of Medicine
  • , Douglas EvansAffiliated withM.D. Anderson Cancer Center
  • , Michael J. LawsonAffiliated withKaiser Permanente, University of California
    • , Suzanne FligielAffiliated withDepartment of Medicine and Pathology, John D. Dingell Veterans Affairs Medical Center, Wayne State University School of Medicine

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Abstract

Background and Aim

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.

Keywords

Pancreatic ductal adenocarcinoma (PDA) Adnab-9 monoclonal antibody K-ras Her-2/neu