Abstract 1141: MAb-PAM4 can differentiate between pancreatic ductal adenocarcinoma and chronic pancreatitis. (2013)

Abstract Background: Due to the asymptomatic nature of pancreatic ductal adenocarcinoma (PDAC) in its early stages of growth, and its relatively low incidence, screening methods have not received high attention. However, with recent studies providing the ability to identify specific patient groups at high risk for PDAC, a rationale exists for longitudinal surveillance as a means to improve early detection specifically in these high-risk settings. Individuals with a family history of PDAC, those patients with long-standing chronic pancreatitis (CP), patients with new-onset diabetes who meet certain other conditions, or those with FAMMM syndrome, etc., could be evaluated on a long-term basis for the detection of early malignant changes by use of a MAb-PAM4-based immunoassay procedure. Methods: We have developed and validated (in over 600 patient specimens) an enzyme immunoassay (EIA) based upon use of MAb-PAM4 for quantitation of antigen in the serum of patients diagnosed with pancreatic ductal adenocarcinoma. In addition, the antibody has been used for immunohistochemical evaluation of malignant, benign, and normal pancreatic tissues. Results: 71% of patients with confirmed early-stage disease and 91% with advanced disease were positive by EIA for circulating PAM4-antigen. Overall specificity was 81% with respect to benign pancreatic disease. Of 126 patients diagnosed with benign conditions of the pancreas, 24 (19%) were positive for the PAM4-antigen, with the majority of these cases being diagnosed with chronic pancreatitis [18 of 80 positive (23%)], all of whom had surgical resection performed for severity and/or duration of disease activity. ROC curve analyses of PAM4 assays revealed a statistically significant difference between the PDAC and CP groups (P&amp;lt;0.0001), with an area under the curve of 0.84 ± 0.02 (95% CI: 0.79-0.89). The positive likelihood ratio for differentiating PDAC from benign conditions of the pancreas was 4.00, which was significant (P&amp;lt;0.001). It is very important to emphasize that the “true” specificity of this assay is likely underestimated. Immunohistochemistry data have shown the PAM4-biomarker is absent from normal pancreas and benign, non-neoplastic lesions of the pancreas. In over 50 surgical specimens of CP, the PAM4-biomarker was identified only within PanIN lesions that are associated with long-term CP, and not by the inflamed tissue. Conclusions: Our results suggest that PAM4-positive CP patients (and likely other PAM4-positive patients diagnosed with benign conditions of the pancreas) may very likely have pancreatic neoplasia (invasive and/or precursor lesions), and therefore should be followed closely. Indeed, such studies might reveal new cutoff values or kinetic changes that would support early surgical intervention. (Supported in part by NIH grant CA096924.) Citation Format: David V. Gold, Chanjuan Shi, Guy Newsome, David M. Goldenberg. MAb-PAM4 can differentiate between pancreatic ductal adenocarcinoma and chronic pancreatitis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1141. doi:10.1158/1538-7445.AM2013-1141