Prospective markers for early diagnosis and prognosis of sporadic pancreatic ductal adenocarcinoma. Dig Dis Sci 2013 Mar;58(3):744-50
Date
09/25/2012Pubmed ID
23001406DOI
10.1007/s10620-012-2387-xScopus ID
2-s2.0-84876685733 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
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.
Author List
Tobi M, Kim M, Weinstein DH, Rambus MA, Hatfield J, Adsay NV, Levi E, Evans D, Lawson MJ, Fligiel SAuthor
Douglas B. Evans MD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAged, 80 and over
Antibodies, Monoclonal
Biomarkers, Tumor
Body Fluids
Carcinoma, Pancreatic Ductal
Feces
Female
Gene Expression Regulation, Neoplastic
Genes, ras
Humans
Male
Middle Aged
Mutation
Pancreatic Neoplasms
Prognosis
Prospective Studies
Retrospective Studies
