EXPRESSION OF CD44 SPLICE VARIANTS IN SQUAMOUS EPITHELIA AND SQUAMOUS-CELL CARCINOMAS OF THE HEAD AND NECK

Splice variants of the adhesion molecule CD44 have been described as e ssential for the lymphatic spread of rat tumour cells and are claimed to be involved in the metastatic spread of several human tumours, Immu nohistochemistry has been used to an analyse the expression pattern of CD44 standard (CD44s) and variant (CD44v) isoforms in normal and dysp lastic squamous epithelia, as well as in primary and metastatic squamo us cell carcinomas (SCCs), which spread predominantly by way of the ly mphatic system. Frozen sections of squamous epithelia and of squamous cell carcinomas were stained with a panel of monoclonal antibodies rec ognizing epitopes of CD44s as well as of the variant exons v5, r6, v7, v7-v8, and v10, The stratum basale and stratum suprabasale of squamou s epithelia stained with all antibodies; the stratum spinosum stained with anti-CD44v5, anti-CD44v6, anti-CD44v7-8 and anti-CD44v10; the low er layers of the stratum corneum stained with anti-CD44v5. This expres sion profile was seen in epithelia of the lip, the tongue, the gingiva , the hard palate, the floor of the month, the buccal mucosa, and the pharynx. The same pattern of expression was also noted in dysplastic e pithelia, hut expression of the variant exons v7, v8, and v10 was sign ificantly downregulated in primary squamous cell carcinomas and was no t detected at all in the majority of metastasis-derived specimens. Exp ression of CD44v5 and CD44v6, on the other hand, was mainly unaltered, Thus, epithelial cell layers representing different stages of differe ntiation express distinct sets of CD44 variant isoforms, where especia lly exons v8-v10 might be required for the maintenance of the structur al integrity of squamous epithelium. Downregulation of these exons on tumour cells could indicate that they are irrelevant for tumour progre ssion or may even hamper infiltration of surrounding tissue or of lymp hatics.