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Background: Our laboratory has developed and characterized MAb PAM4, demonstrating high specificity for MUC1 expressed by pancreatic adenocarcinoma as compared to other forms of cancer, normal pancreas, or pancreatitis. We have also reported its sensitivity and specificity in a serum immunoassay, its use for imaging of invasive pancreatic adenocarcinoma, and its potential for a targeted therapy of this disease. Clinical trials for radiolabeled PAM4-imaging/therapy are ongoing. In order to evaluate PAM4-reactive MUC1 in early pancreatic neoplasia, we examined its expression in pancreatic intraepithelial neoplasia (PanIN) as noninvasive precursor lesions within pancreatic ducts. Methods and Results: Immunohistochemical labeling of tissue microarrays was performed. Positive labeling of PanIN lesions was observed in 94% (44/47) PanIN-1 lesions, 91% (10/11) PanIN-2 lesions, 40% (2/5) PanIN-3 lesions, and 92% (33/36) of invasive adenocarcinomas. Although the percentage of PAM4-reactive PanIN-3 specimens was lower than for other PanIN groups, this difference was not statistically significant. Labeling of non-neoplastic ducts was not observed with PAM4. A second anti-MUC1 MAb, MA5, reactive with the VNTR peptide core, demonstrated considerably less sensitivity with the early lesions: 61% (25/ 41) PanIN-1 lesions were positive (P<0.001 compared to PAM4 results), as were 38% (3/8) PanIN-2 lesions (P<0.01), 100% (7/7) PanIN-3 lesions (P<0.05), and 100% (33/33) of invasive adenocarcinomas. The MA5 anti-MUC1 antibody also was reactive with normal and inflammatory tissues of the pancreas and other MUC1-expressing tissues. Finally, an anti-MUC2 antibody, G9, was relatively nonreactive with PanINs (8/57, or 14% positive), as well as invasive adenocarcinomas (1/36, or 3% positive). Conclusions: These results suggest that the PAM4-reactive MUC1 epitope appears as an early event in the progression of genetic and morphologic events that ultimately culminate in invasive adenocarcinoma of the pancreas. The PAM4-epitope may aid in the interpretation of biopsy specimens. (Supported in part by USPHS grant CA096924 from the NIH.)

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA