Distribution of integrins and extracellular matrix proteins in vulvar squamous cell carcinomas

We report the topography of integrins and some basement membrane zone (BMZ) proteins in normal vulvar skin and in seven cases of vulvar squamous carcinoma (VSC). In vulvar epidermis integrin chains alpha 2, alpha 3 and beta 1 lined the lateral surface of basal cells, while the heterodimer alpha 6 beta 4 was detected only at their basal domain. The location of alpha 6 beta 4 exactly matched BMZ identified by kalinin, laminin and collagen type IV. In VSC this pattern was subverted since both beta 1 integrins and alpha 6 beta 4 became pericellular. In particular, alpha 6 beta 4 lost its coherence with the residual organization of BMZ. In fact, BMZ components displayed their normal pattern were this was preserved, and so were fibronectin and tenascin in the stroma underlying the tumor. Furthermore, alpha 5 beta 1, the prototype fibronectin receptor that is not normally exposed in vulvar epidermal cells, became detectable pericellularly in VSC tumor cells. Alteration of integrin polarized topography appears to be typical of VSC cells as well as of other tumor epidermal cells. This alteration may be easily shown by immunohistochemistry on routinely collected frozen biopsies. It may then represent a tool for the early diagnosis of VSC that provides a quick and easy complement of traditional histology.