Purification, partial characterization, and clinical evaluation of a pancreatic oncofetal antigen.

This paper describes the purification and partial char acterization of a putative pancreatic oncofetal antigen. Pancreatic oncofetal antigen is a glycoprotein with a molecular weight between 800,000 and 900,000, which migrates in the af to /3-region on electrophoresis. It is found in fetal pancreas and pancreatic cancer tissue, but it is not found in normal adult pancreas. Highly purified material migrated as a single band on polyacrylamide gel electrophoresis and immunized rabbits to produce monospecific antibody without absorption. Pancreatic oncofetal antigen is clearly different from carcinoembryonic anti gen, other known tumor-associated antigens, acutephase reactants, and normal serum proteins. In addition, a quantitative rocket immunoelectrophoresis assay sen sitive enough to detect pancreatic oncofetal antigen in the serum of most patients was developed and used to monitor the purification of pancreatic oncofetal antigen and to evaluate its clinical application. Assays for pancreatic oncofetal antigen were carried out on three panels of sera; one was collected at The University of Chicago, and two were supplied by the Mayo-National Cancer Institute Serum Plasma Bank. The results demonstrate that pancreatic oncofetal antigen is found in the sera of most individuals; however, by far the highest absolute levels and the highest frequency of elevated levels were found in sera of patients with carci noma of the pancreas. Elevated levels of pancreatic oncofetal antigen were also observed in the serum of some patients with carcinoma of the lung, stomach, colon, biliary tract, and breast as well as in the serum of some pregnant women and other individuals with certain benign conditions. The spectrum of patients who have elevated levels of pancreatic oncofetal antigen in their serum is quite different from that found with carcinoembryonic antigen or other known tumor markers. Serial assays were performed on the sera of several patients with cancer of the pancreas; the results suggest that measure ment of pancreatic oncofetal antigen may be valuable in monitoring the course of cancer of the pancreas. 1 Supported in part by USPHS Grants CA 17525 and CA 14599 and by Contract NO1-CB-43976. 2 Supported by a postdoctoral fellowship from USPHS Training Grant A1 452. To whom requests for reprints should be addressed, at Department of Pathology, The University of Chicago, Box 414, 950 East 59th Street Chicago, III. 60637. 3 Recipient of USPHS Research Career Development Award CA 00032. 'Operated by The University of Chicago for the U. S. Energy Research and Development Administration under Contract EY-76-C-02-0069. Received November 8, 1976; accepted November 8, 1977. INTRODUCTION Recently, there has been an increasing interest in the diagnostic and prognostic usefulness of tumor-associated antigens of embryonic and fetal origin. Two oncofetal antigens have been extensively investigated. AFP5 appears in the serum of patients with hepatoma and embryonal carcinoma (1, 2). CEA is most closely associated with carcinoma of the digestive tract and bronchopulmonary tree (13). In 1974, Banwo ef a/. (5) reported finding another oncofetal antigen in extracts of fetal pancreas, pancreatic tumor nodules, and sera from patients with carcinoma of the pancreas. They did not detect this antigen in the sera of patients with a variety of other diseases or in extracts of normal adult pancreas. In an attempt to reproduce these results, we have demonstrated an oncofetal antigen that appears to be associated with the pancreas. Since material from Banwo ef al. (5) has not been available to us for comparison, we have not been able to determine whether the antigen that we have isolated is identical with that demonstrated previously. However, our antigen is clearly different from CEA and AFP. This report details the isolation and partial characterization of this antigen, which we call "pancreatic oncofetal antigen", and presents the results of assays on over 700 sera from patients with a variety of disorders. MATERIALS AND METHODS Sample Collection. Tissues from human fetuses of 18to 20-week gestation were obtained within 3 hr of prostaglandin-induced abortions. Adult tissues were obtained from surgical specimens or from autopsies within 12 hr of death. All tissues were processed immediately or stored at -20° until processed. Serum samples from patients with various abdominal diseases were collected over a 2-year period and stored at -70°. One selected patient with pancreatic cancer and elevated pancreatic oncofetal antigen levels underwent plasmaphoresis, and the plasma was stored at -20°.Ascitic fluid from 5 patients with pancreatic cancer was obtained at the time of autopsy. The diagnosis for all patients was confirmed by review of the hospital charts, surgical and pathology reports, slides, and photographs. The patient sera used in the quantitative assays for pancreatic oncofetal antigen were obtained from 3 sources. First, a panel of 100 coded samples was received from the Mayo-NCI Serum Plasma Bank on September 16, 1975. This panel contained sera from 25 patients with carcinoma 5 The abbreviations used are: AFP, «-fetoprotein; CEA, carcinoembryonic antigen; NCI, National Cancer Institute; PBS, 0.01 M phosphate-0.85% NaCI; SDS. sodium dodecyl sulfate; Con A. concanavalin A.