First, the M1 mucins are defined by immunohistology on normal and cancerous gastrointestinal tract using polyclonal antibodies (1). Anti-M1antibodies stained the columnar mucus cells of the surface epithelium of gastric mucosa (Fig 1) and goblet cells of the fetal (2) and precancerous colon mucosae: adenomas (3) (Fig 3) or mucosae adjacent to adenocarcinomas (4) (Fig 4) exclusively. The normal colon mucosae were never stained by the anti-M1 antibodies (Fig 2). During the rat colon carcinogenesis, these M1 antigens were expressed early, two weeks after the first injection of carcinogen (5). Then these M1 mucins can be regarded as early markers of colon carcinogenesis. In the pancreas, the expression of M1 mucin has been described in the human pancreatic capan-1 cell line (6) and was expressed in 93% (82/88) of human pancreatic ductal adenocarcinomas (7) . M1 mucin is also associated to mucinous cystadenomas of the pancreas, a precancerous lesion. This M1 mucin is a good tumor marker of early pancreatic carcinogenesis and is useful to improve the diagnosis of pancreatic mucinous cystadenomas in estimating the level of M1 mucin in pancreatic cyst fluids (8) using Immunoradiometric Assay. Figures 1, 2, 3 and 4

Later, we obtained 8 different monoclonal antibodies showing the same staining on gastrointestinal tract than polyclonal antibodies. 7 different M1 epitopes are characterised as associated to peptide core of mucin and called M1-a, -b, -c, d, -e, -f and -g (9, 10). Indeed, these M1 epitopes were excluded from Sepharose Cl-2B corresponding to very high molecular weight as known for the mucin. They were destroyed by mercaptoethanol (excepted the M1-f) , partially by trypsin and not by periodic acid (11).

Recently, using the baculovirus/Sf9 system, we demonstrated that a recombinant virus containing the 3'end of the MUC5AC cDNA expressed the M1-f epitope demonstrating that MI immunoreactivity is encoded by the MUC5AC gene (12).

An Immunoradiometric Assay (IRMA) allows to detect M1 mucin in biological fluids. This test is useful to precise the diagnosis of mucinous (precancerous) pancreatic cystadenomas and may in the future to screen high risk population for colon cancer.

  By Immunoperoxidase, using antiserum against mucins isolated from gastrointestinal tssues and ovarian mucinous cyst fluis, after extensive absorption with blood red cells and tissus exptracts 3 type of immunchemically different mucins were observed. Mucins associated with surface gastric epithelium (M1 antigens), mucins associated with gastric and B'ünner's glands (M2 antigens) and mucins associated with intestinal goblet cells (M3 antigens) (Fig. 5, 6, 7). Two subclass of M3 antigens were described. The M3SI antigen associated with mucin secreted by small intestine goblet cells and the M3C immunoreactivity restricted to colon goblet cells (Fig 8, 9)

Later, using in situ hybridization , the same tissue specific location could be observed/: MUC5AC gene was expressed in the surface gastric epithelium as M1 antigens, MUC6 expression was restricted to gastric and Brünner's glands as M2 antigens, MUC-2 mainly expressed by intestine as M3 antigens.

Up to day, we demonstrated that M1 immunoreactivity is encoded by MUC5AC gene using the baculovirus/insect cells system.

(1) - J. BARA, F. LOISILLIER & P. BURTIN. Antigens of gastric and intestinal mucous cells in human colonic tumours. Br. J. Cancer, 41, 209-221 (1980).

(2) - J. BARA & P. BURTIN. Mucus associated gastrointestinal antigen in transitional mucosa adjacent to human colonic adenocarcinomas: their " fetal type " association. Europ. J. Cancer: 16, 1303-1310 (1980).

(3) - J. BARA , O. LANGUILLE, M.C. GENDRON, N. DAHER, E. MARTIN & P. BURTIN. Immunohistological study of precancerous modification in human distal colonic polyps. Cancer Res. 43 : 3885-3891, (1983).

(4) - J. BARA, J. ANDRE, R. GAUTIER & P. BURTIN. Abnormal pattern of mucus associated M1 antigens in histologically normal mucosa adjacent to colonic adenocarcinomas. Cancer Res: 44, 4040-4045 (1984)

(5) - C. DECAENS, J. BARA, B. ROSA, N. DAHER & P. BURTIN. Early oncofetal antigenic modifications during rat colonic carcinogenesis. Cancer Res. 43: 355-362 (1983).

(6) - E. HOLLANDE, V. TROCHERIS DE ST FRONT, P. LOUET-HERMITTE, J. BARA, J. PEQUIGNOT, A. ESTIVAL & F. CLEMENTE. Difference features of human pancreatic tumor cells maintained in nude mice and in culture: immunocytochemical and ultrastructural studies. Int J. Cancer : 34, 177-185 (1984).

(7) - F. SESSA, M. BONATO, B. FRIGERIO, C. CAPELLA, E. SOLCIA, M. PRAT, J. BARA and I.M. SAMLOFF. Gastrointestinal markers are largely expressed in pancreatic duct cancers but not in ductular, centroacinar or acinar cell tumors. An histological, histochemical and ultrastructural study of 105 tumors. Gastroenterology: 98:1655-1665 (1990).

(8) - HAMMEL, P., FORGUE-LAFITTE M.E., LEVY, P. VOITOT, H., VILGRAIN, V., FLEJOU, J-F., MOLAS, G., GESPACH, C., RUSZNIEWSKI, P., BERNADES, P., and BARA, J. Combined detection of gastric mucins (M1 antigens) and CEA in cyst fluid improve the preoperative differential diagnosis of cystic lesions of the pancreas. Int. J. Cancer, 74:286-290 1997.

(9) - J. BARA, R. GAUTIER, N. DAHER, H. ZAGHOUANI & C. DECAENS. Monoclonal antibodies against oncofetal mucin M1 antigens associated with precancerous colonic mucosae. Cancer Res. 46: 3983-3989 (1986).

(10) - J. BARA, GAUTIER, R., MOURADIAN, P., DECAENS, C. and DAHER, N., Oncofetal mucin M1 epitope family: characterization and expression during colonic carcinogenesis. Int. J. Cancer, 47, 304-310 (1991).

(11) - J. BARA, R. GAUTIER, J. LE PENDU & R. ORIOL. Immunochemical characterization of mucins: Polypeptides (M1) and Polysaccharide (A and Lewis) Antigens. Biochem. J. 254: 185-193 (1988).

(12) - BARA J., CHASTRE, E., MAHIOU, J., SINGH, R.L., FORGUE LAFITTE, M.E., HOLLANDE, E., and GODEAU, J-F. Gastric M1 mucin, an early oncofetal marker of colon carcinogenesis, is encoded by the MUC5AC gene. Int. J. Cancer 75: 767-773 (1998).