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Loss of a Novel Mucin-like Epithelial Glycoprotein in Oral and Cervical Squamous Cell Carcinomas¹

Department of Oral Diagnostics, Faculty of Health Sciences, School of Dentistry, University of Copenhagen, 2200 Copenhagen N, Denmark [P. A. N., U. M., C. A. R., H. H. W., E. D., H. C.]; Department of Pathology, Rigshospitalet, 2100 Copenhagen Ø, Denmark [M. H. T., V. R.]; Department of Pathology, Frederiksberg Hospital, 2000 Frederiksberg, Denmark [V. R.]; and Department of Pathology, Institute of Molecular Pathology and Immunology of the University of Porto, Hospital S. João, 4200 Porto, Portugal [L. D., C. A. R.]

Stratified squamous epithelia of oral and cervical mucosa express high levels of simple mucin-type O-linked carbohydrates, and these are known to undergo structural changes in relation to epithelial differentiation and neoplastic transformation. O-glycans in these epithelia are associated with the cell membrane, but the identity of the carrier molecule(s) remains largely unknown. We report here the identification of a membrane-bound M_r 200,000–250,000 glycoprotein (gp230) that is expressed in stratified squamous epithelia of the oral cavity. Western blot analysis identified gp230 as a major carrier of simple-mucin type carbohydrate antigens in buccal nonkeratinized mucosal epithelium, suggesting that it may represent a mucin-like molecule. A monoclonal antibody PANH4 defining a protein epitope of gp230 was generated. The PANH4 epitope was localized by immunohistology to suprabasal cell layers of buccal epithelium and was also found in larynx, esophagus, vagina, and exocervix, but not in epidermis. Data showed that gp230 was distinct from MUC1 or CD44. It is interesting that in most cases gp230 was not expressed in squamous cell carcinomas of buccal and cervical mucosa. A few moderately differentiated carcinomas, mainly from cervix, expressed the gp230 epitope. The results suggest that a membrane-bound mucin-like molecule, gp230, is associated with the differentiated phenotype of normal mucosal stratified squamous epithelia and that expression of gp230 generally is lost in severe oral epithelial dysplasia and squamous cell carcinomas of oral and cervical mucosa.

¹ This study was supported by The Danish Cancer Society, Ingeborg Roikjer Foundation, The Danish Medical Research Council. The Lundbeck Foundation, and JNICT (PECS/C/SAV/255/95).

² To whom requests for reprints should be addressed, at Department of Oral Diagnostics, School of Dentistry, Nørre Alle 20, 2200 Copenhagen N., Denmark. Phone: 45 35326836; Fax: 45 35326833; E-mail: pn@odont.ku.dk.

Received 9/24/96. Accepted 12/18/96.

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