Digestive Diseases and Sciences. VoL 40, No. 7 (July 1995). pp. 1531-1537 A Urinary Organ Specific Neoantigen Potentially Diagnostic Test for Colorectal Cancer MARTIN TOBI, MB, ChB, ELIZABETH DARMON, MSc, PAUL ROZEN, MBBS, NURIT HARPAZ, MSc, ARON FINK, MD, PhD, BENEDICT MALIAKKAL, MD, ALLAN HALLINE, MD, SOHRAB MOBARHAN, MD, and ZVI BENTWICH, MD Urinary organ-specific neoantigen from colorectal cancer patients has been used to make a monoclonal antibody, BAC 18.1. In this study we assessed the potential of this antibody for the diagnosis of colorectal cancer. We evaluated binding in both urine and effluent samples and compared it with effluent carcinoembryonic antigen standardized for both volume (nanograms per milliliter) and protein. Urinary organ-specific antigen as detected by BAC 18.1 was significantly greater in 29 cancer patients (A4o5:0.717 +_ 0.500) vs 27 controls [0.121 +_ 0.273 (P < 0.05)]. Considerable overlap of binding of BAC 18.1 was observed in the colonic effluent of patients with CRC (N = 13), adenomas (N = 26), inflammatory bowel disease (N = 8), or having a normal colonoscopic examination (N --- 24). CEA levels (nanograms per milliliter) were significantly elevated in the effluent samples of patients with a past history of colorectal cancer, as compared to that of normal individuals (P < 0.05). The presence of the Mr 30,000 organ-specific neoantigen in colonic effluent was also demonstrated by western blot. Organ-specific neoantigen originates in the colon and is excreted into the urine, so the BAC 18.1 binding levels in the urine may be a diagnostic aid for CRC. KEY WORDS: monoclonal antibody; colorectal cancer; leukocyte adherence inhibition; carcinoembryonic antigen. Newer diagnostic tests for colorectal cancer (CRC) are being developed based on recently acquired knowledge of the biology of the disease (1). These and other tests (2) rely on the detection of tumor markers or components shed into the colonic lumen. The heavy bacterial load, with its multitude of degra- dative enzymes, poses an obstacle to the successful Manuscript received February 20, 1994; revised manuscript re- ceived December 19, 1994; accepted March 17, 1995. From the Department of Gastroenterology, Tel Aviv Medical Center, 6 Weizman St, Tel Aviv; The Ben-Ari Immunological Institute, Kaplan Hospital, Rehovot, Israel; Division of Gastroen- terology, Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan; Division of Gastroenterology, University of Illinois at Chicago, Chicago, Illinois; and Loyola University Medical Center, Maywood, Illinois. The work reported in this paper was supported in part by a grant from the Israeli Cancer Association and Tel Aviv University, and in part by grants from the Israel Cancer Association and the Sackler School of Medicine, Tel Aviv, Israel. Address for reprint requests: Dr. Martin Tobi, Division of Gas- troenterology, Wayne State University Medical School, Harper Hospital, 3990 John R St., Detroit, Michigan 48201. development of potentially diagnostic tests based on the colonic shedding of neoplasia markers. Methods to decrease protease breakdown of protein determi- nants in precolonoscopic washing (effluent) collec- tion, which reduce bacterial contamination, have been used (3, 4). A tumor marker that is either not substantially degraded (5) or, alternatively, one that is detectable by the use of antibodies for preserved epitopes on the protease breakdown products (6) may be used. Another approach that we have combined with the above is to assess CRC tumor markers that may be small enough to be filtered into the urine. The putative organ-specific neoantigen (OSN) is a Mr 30,000 protein moiety isolated from the urine of patients with cancer and appears to mediate the leu- kocyte adherence inhibition (LAI) test. The LAI test depends on the ability of lymphocytes, which have been exposed and sensitized to a specific antigen, to secrete lymphokines when reexposed to that antigen Digestive Diseases and Sciences, Vol. 40, No. 7 (July 1995) 0163.2116/95/0700-1531507.50/0 91995PlenumPublishing Corporation 1531