The pattern of expression of the 5T4 oncofoetal antigen on normal, dysplastic and malignant oral mucosa A. Ali a , J. Langdon a , P. Stern b , M. Partridge a, * a Maxillofacial Unit/Molecular Oncology, King's College Hospital, Denmark Hill, London SE5 8RX, UK b Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK Received 16 February 2000; accepted 27 March 2000 Abstract The human 5T4 oncofoetal antigen is expressed by all types of trophoblast in pregnancy but is not detected on most adult tissues, although low levels are found on some epithelia. However, this antigen is strongly expressed by many cancers and tumour- associated labelling correlates with metastatic spread and poor clinical outcome for patients with gastric and colon cancer. Over- expression of the gene in¯uences cell adhesion, shape and motility, which may be related to changes in the cellular localisation of the 5T4 oncofoetal antigen as malignancy develops. To establish whether the 5T4 oncofoetal antigen can serve as a tumour-speci®c marker for oral cancer and precancer, we have evaluated the pattern of expression on biopsies of normal, in¯amed and dysplastic oral mucosa using immunohistochemistry. Oral mucosa, taken from dierent sites in the mouth, expressed the 5T4 oncofoetal antigen with varying intensity and pattern. The majority of the immunoreactivity was detected in the basal and suprabasal layers, with expression extending into the spinous cells at fully keratinised sites and when in¯ammation was present. This antigen was also detected in the underlying connective tissue. Oral squamous cell carcinoma showed a variety of patterns and intensity of staining corresponding to those found for normal mucosa. However, 21 of 41 cases showed no stromal labelling, a ®nding also observed for dysplastic lesions. The alterations in the pattern and intensity of 5T4 oncofoetal antigen expression were not related to clin- icopathological features of the tumours examined. These data show that the 5T4 oncofoetal antigen is expressed on normal oral mucosa, such that this target cannot be used for detection of neoplastic or preneoplastic cells, although altered expression may contribute to the pathogenesis of these lesions. # 2001 Elsevier Science Ltd. All rights reserved. Keywords: Oral cancer; Precancer; Biomarkers; Oncofoetal antigens; Tumour markers 1. Introduction At present the decision as to whether or not to treat patients with precancerous lesions is largely based on clinical intuition and the severity of dysplasia. However, the clinical appearance of precancerous lesions can be misleading when trying to identify those which will ultimately become neoplastic. Histological assessment is also unreliable because of the subjectivity inherent in this approach and the dierent histological criteria used to de®ne dysplasia in dierent centres. Thus it would be enormously helpful to have additional markers which could be used when making critical decisions about treatment. Progress in this area has been made by identifying monoclonal antibodies which de®ne antigens that share expression on human trophoblast cells (which allow the foetus to invade and form a placenta) and many carci- nomas. Such candidate markers which are likely to in¯uence a process of tumour invasion should show only restricted normal tissue expression. The 5T4 onco- trophoblast antigen is considered to meet these criteria [1,2]. High levels of transcripts for this antigen can be detected in both the mouse embryo and placenta [3], suggesting that its expression may in¯uence several processes which occur during embryogenesis, where migration or motility of cells, adhesion and anti- adhesion cell-to-cell interactions are pivotal. Expression of this marker is associated with poorer clinical out- come in colorectal [4,5], gastric [6] and ovarian cancer [7]. In addition, the level of expression increases with the degree of dysplasia when cervical intra-epithelial 1368-8375/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved. PII: S1368-8375(00)00057-9 Oral Oncology 37 (2001) 57±64 www.elsevier.com/locate/oraloncology * Corresponding author. Tel.: +44-20-7346-3474; fax: +44-20- 7346-3754.