Mucosal Origin and Shedding of an Early Colonic Tumor Marker Defined by Adnab-9 Monoclonal Antibody

Abstract

Recent attention has been drawn to the diagnostic potential of tests based on shed colonic tumor markers. Adnab-9 monoclonal antibody raised against neoplastic, potentially premalignant colonic adenomas recognizes a marker in colonic effluent or tissue which correlates with the presence of tumors or risk of colorectal cancer. The origin of this antigen and optimal collection of colonic effluent were investigated by enzyme-linked immunosorbent assay and Western blotting. Mean Adnab-9 binding in effluent samples from colorectal cancer patients even after resection is high as compared with that in normal subjects (P < 0.05). Effluent samples are best collected in the morning hours. Antigen proteolysis may be significant depending on the site and timing of effluent collection, but breakdown products are reactive. Tissue and effluent Adnab-9 binding at any one anatomic site of collection appear to correlate (r = 0.88, P = 0.01). The Adnab-9 antigen is constitutively expressed at low levels throughout the distal bowel and localized to the deepest regions of the mucosal crypts. Other than meconium, no significant levels of binding are found in other body fluids. This antigen is specific for the gastrointestinal tract, its binding in conveniently collected effluent samples correlates with tissue content, and the antigen is constitutively expressed in the crypts of the distal small bowel and colonic mucosa.

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

“…We used an enriched PCR method to detect K-ras mutations as previously described [24]. ELISA was performed with Adnab-9, anti-Her-2/neu, and monoclonal antibody D4 (anti Reg I) as previously described [6]. All ELISA quantifications used optical density of the extract plated out at 5 lg protein/well after Dig Dis Sci subtracting the background.…”

“…The Adnab-9 monoclonal antibody has shown promise as a diagnostic and premalignant marker for colorectal [6,7], gastric [8] and small intestine adenocarcinoma [9]. In those studies, neoplastic Paneth cells are often identified.…”

Polyps as biomarkers for colorectal neoplasia

“…The antibody displays differential binding to adenomas and appears to recognize a subset of cells deep within the substance of the adenoma (78). Subsequently, some of these cells have been identified as Paneth-like cells (figure 1) in tissues with or at risk for CRC (79). Paneth cells in APC patients have been shown to secrete epidermal growth factor (80), a ligand for a receptor that, once activated, is mediated by tyrosine kinase.…”

Differential Labeling by Monoclonal Antibodies Adnab-9 and Anti-?-Defensin 5 Based on the Distribution and Adenomatous Tissue Content of Colonic Polyps

“…Differences in each category were analyzed by the comparison of proportions using Fisher's exact test and least squares test for linear correlation between variables, as described previously (15)(16)(17)(18). Significance was defined as P < 0.05.…”

“…Adnab-9 binding has been shown to identify a subpopulation of cells in colonic adenomatous and normal mucosa from colons bearing CRC, but not carcinomatous tissue, some of which resemble Paneth cells (PC) (13)(14)(15)(16). The presence of Adnab-9 staining in nonneoplastic colonic epithelium has been shown to be associated with an increased risk for development of colorectal cancer (13)(14)(15)(16)(17). In addition, Adnab-9 staining has a positive correlation with multiplicity and recurrence of colonic polyps and may be a predictor of future development of dysplastic polyps with recognized malignant potential in these patients (18).…”