mAb Das-1 is specific for high-risk and malignant intraductal papillary mucinous neoplasm (IPMN)

Abstract

Objective Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes that correlate with histological grades and risks for malignant transformation. mAb Das-1 is a monoclonal antibody against a colonic epithelial phenotype that is reactive to premalignant conditions of the upper GI tract. We sought to assess the ability of mAb Das-1 to identify IPMN with high risk of malignant transformation. Design mAb Das-1 reactivity was evaluated in 94 patients with IPMNs by immunohistochemistry. Lesional fluid from 38 separate patients with IPMN (n=27), low-grade non-mucinous cystic neoplasms (n=7) and pseudocysts (n=4) was analysed by ELISA and western blot. Results Immunohistochemistry Normal pancreatic ducts were non-reactive and low-grade gastric-type IPMN (IPMN-G) (1/17) and intermediate-grade IPMN-G (1/23) were minimally reactive with mAb Das-1. In contrast, mAb Das-1 reactivity was significantly higher in high-risk/malignant lesions (p<0.0001) including: intestinal-type IPMN with intermediate-grade dysplasia (9/10); high-grade dysplasia of gastric (4/7), intestinal (12/12), oncocytic (2/2) and pancreatobiliary types (2/2); and invasive tubular (8/12), colloid (7/7) and oncocytic (2/2) carcinoma. The sensitivity and specificity of mAb Das-1 for high-risk/malignantIPMNs were 85% and 95%, respectively. Lesional fluid Samples from low- and intermediate-grade IPMN-G (n=9), and other low-grade/benign non-mucinous lesions demonstrated little reactivity with mAb Das-1. Conversely, cyst fluid from high-risk/malignant IPMNs (n=18) expressed significantly higher reactivity (p<0.0001). The sensitivity and specificity of mAbDas-1 in detecting high-risk/malignant IPMNs were 89% and 100%, respectively. Conclusions mAb Das-1 reacts with high specificity to tissue and cyst fluid from high-risk/malignant IPMNs and thus may help in preoperative clinical risk stratification.

Updates and Critical Evaluation on Novel Biomarkers for the Malignant Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas

“…Both the EUS-FNA cyst fluid analysis (specificity and sensitivity of 100% and 89%, respectively) and histological specimens from resected high-grade IPMNs (specificity and sensitivity of 95% and 85%, respectively) showed that Das-1 has potent reactivity (69).…”

Intraductal Papillary Mucinous Neoplasms of the Pancreas: Strategic Considerations

“…In a collaborative effort with the Rutgers Robert Wood Johnson Medical School, we have also found that mAb Das-1, a monoclonal antibody that reacts specifically with normal colonic epithelium and intestinal metaplasia of the lower esophagus (Barrett's esophagus), can identify high-risk IPMN using cyst fluid with a sensitivity and specificity of 89 and 100%, respectively [55]. A preliminary, multi-institutional validation study of the performance of mAb Das-1 confirmed our initial findings and suggests that this antibody may be a valuable addition to current clinical guidelines [56].…”

Cyst Fluid Biomarkers - Diagnosis and Prediction of Malignancy for Cystic Lesions of the Pancreas

“…One other promising marker for identifying IPMNs which require surgical resection is mAb Das-1, a monoclonal antibody which is found in premalignant conditions of the gastrointestinal tract. In preliminary studies, it had 85% sensitivity and 95% specificity for identifying IPMNs with high-grade dysplasia or invasive cancer and is now being evaluated in a multicenter study [33]. …”