ABSTRACT
Given the need to improve the sensitivity of non-invasive methods to detect colorectal neoplasia, particularly adenomas, we compared a fecal test using a monoclonal antibody (Mab) raised against constituents of colonic adenomas designated Adnab-9 (Adenoma Antibody 9), recognizing an N-linked 87 kDa glycoprotein, to gFOBT, which is shown to reduce CRC mortality. p87 immunohistochemistry testing is significantly more sensitive (OR 3.64[CI 2.37-5.58]) than gFOBT (guaiac-based fecal occult blood test) for adenomas (<3 in number), advanced adenomas (OR 4.21[CI 2.47-7.15]), or a combination of the two (OR 3.35[CI 2.47-4.53]). p87 immunohistochemistry shows regional Paneth cell (PC) expression mainly in the right-sided colon and is significantly reduced in the ceca of African Americans (p < 0.0001). In a subset of patients, we obtained other body fluids such as urine, colonic effluent, and saliva. Urine tests (organ-specific neoantigen) showed a significant difference for advanced adenomas (p < 0.047). We conclude that fecal p87 testing is more sensitive than gFOBT and Adnab-9 and could be used to better direct the colonoscopy screening effort.
Subject(s)
Adenoma , Colorectal Neoplasms , Humans , Guaiac , Occult Blood , Mass Screening/methods , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Colonoscopy/methods , Adenoma/diagnosis , Sensitivity and Specificity , Early Detection of Cancer/methodsABSTRACT
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.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Pancreatic Ductal/metabolism , Pancreatic Neoplasms/metabolism , Aged , Aged, 80 and over , Biomarkers, Tumor/chemistry , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Body Fluids/chemistry , Carcinoma, Pancreatic Ductal/blood , Carcinoma, Pancreatic Ductal/diagnosis , Feces/chemistry , Female , Gene Expression Regulation, Neoplastic , Genes, ras , Humans , Male , Middle Aged , Mutation , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/diagnosis , Prognosis , Prospective Studies , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Retrospective StudiesABSTRACT
BACKGROUND AND PURPOSES: Most colorectal tumors develop from adenomatous polyps, which are detected by colonoscopy. African Americans (AAs) have higher incidence of colorectal cancer (CRC) and greater mortality from this disease than Caucasian Americans (CAs). We investigated whether differences in predisposition to CRC and its surrogate (colonic adenomas) between these ethnic groups were related to numbers of cancer stem or stem-like cells (CSCs) in colonocytes. METHODS: We analyzed colonic effluent from 11 AA and 14 CA patients who underwent scheduled colonoscopy examinations at the John D. Dingell Veterans Affairs Medical Center. We determined proportions of cells that expressed the CSC markers CD44 and CD166 by flow cytometry. RESULTS: The proportion of colonocytes that were CD44(+)CD166(-) in effluent from patients with adenomas was significantly greater than from patients without adenomas (P = 0.01); the proportion of CD44(+)CD166(+) colonocytes was also greater (P = 0.07). Effluent from AAs with adenomas had 60 % more CD44(+)166(-) colonocytes than from CAs with adenomas. Using cutoff values of 8 % for AAs and 3 % for CAs, the proportion of CD44(+)166(-) colonocytes that had positive predictive value for detection of adenomas was 100 % for AAs and CAs, determined by receiver operator characteristic curve analysis. CONCLUSION: The proportion of CD44(+)166(-) colonocytes in colonic effluent can be used to identify patients with adenoma. AAs with adenomas have a higher proportion of CD44(+)166(-) colonocytes than CA. The increased proportion of CSCs in colonic tissue from AA might be associated with the increased incidence of CRC in this population.