Use of pancreas-specific antigen in immunodiagnosis of pancreatic cancer

A pancreas-specific antigen was identified by immunologic techniques and purified to electrophoretic homogeneity from saline extract of human pancreas. By immunohistochemical and immunoprecipitation techniques, the pancreas-specific antigen was found in pancreas alone, but not in other human tissues. The purified pancreas-specific antigen exhibited a molecular weight of 44,000 as estimated by gel filtration or SDS-gel electrophoresis, and a sedimentation coefficient of 3.4S as analyzed by sucrose gradient centrifugation. The pancreas-specific antigen possessed an isoelectric point of 4.9 and migrated to α-β region upon immunoelectrophoresis. Enzyme assay procedures demonstrated that the pancreas-specific antigen exhibited no enzymatic activity, including amylase, protease, esterase, lipase, acid phosphatase, alkaline phosphatase, peroxidase, deoxyribonuclease, or ribonuclease. A higher concentration of the pancreas-specific antigen was detected in pancreatic juice than in the saline extract of pancreas. The immunohistochemical study revealed that the pancreas-specific antigen was located in acinar cells of normal human pancreas. In contrast with the result of normal pancreas, the pancreas-specific antigen was localized in ductal cells of pancreas tumor, indicating that pancreatic ductal adenocarcinoma expressed this normal acinar cell protein. Furthermore, the pancreas-specific antigen was found to be expressed in human pancreatic ductal carcinoma cell lines, BxPC-3(primary tumor), MIA PaCa-2(primary tumor), and AsPC-1 (metastatic tumor), as examined in in vitro cell culture and in vivo pancreatic tumor xenografts. A sensitive sandwich-type enzyme immunosorbent assay has been developed for quantitation of pancreas-specific antigen. With this method, the pancreas-specific antigen at a concentration as low as 0.8 ng per ml can be detected. The assay was reproducible as shown by coefficient of variation for within- (4.8 per cent) and between-assays (6.1 per cent). The sensitivity and specificity of serum pancreas-specific antigen test for the detection of pancreatic cancer were calculated to 66 and 95 per cent, respectively. These results indicate tha pancreas-specific antigen was expressed in pancreas tumor of ductal cell origin, and that serum pancreas-specific antigen test may be potentially useful as an adjunctive method in immunodiagnosis of pancreas cancer.