Monoclonal Antibodies against Oncofetal Mucin M1 Antigens Associated with Precancerous Colonic Mucosae

Abstract

We obtained seven monoclonal antibodies (MAb) against a gastric mucin of an ALe^b patient. By immunoperoxidase on normal gastric mucosae, two MAbs (3-3A and 2-25LE) reacted exclusively with the A and Lewis-positive individuals, respectively; the five other MAbs (1-13 M1, 2-11 M1, 2-12 M1, 9-13 M1, and 58 M1) stained the mucus cells of surface gastric epithelium independently of ABO or Lewis status. They did not stain normal colonic mucosae, but did stain fetal and precancerous colonic mucosae. Using serial sections, each anti-M1 MAb stained the same goblet cells in fetal and precancerous colon. Extensive search of other normal tissues showed that M1 antigens were restricted to the epithelium embryologically derived from the foregut (gastric and bronchial epithelium) and from Müllerian ducts (mucus cells of endocervix and prostatic utriculus). Some differences in the reactivities of the various anti-M1 MAb were observed in subesophageal, subtracheal, and endocervical mucus cells, suggesting that each anti-M1 MAb characterized a different M1 epitope. A mixture of these five anti-M1 MAbs allowed the estimation of M1 mucus modification in the precancerous colonic mucosae with a sensitivity near to that obtained with polyclonal anti-M1 antibodies. Papain and mercaptoethanol treatments destroyed the M1 epitopes, at variance with the A- or Lewis-related antigens. Our results therefore suggest that the expression of M1 epitopes in precancerous colonic mucosae cannot be due exclusively to alterations in mucin glycosylation but may be related to the reexpression of antigens associated with native gastric mucin which is normally produced by the fetal colon during the sixth month of gestation.