We demonstrated that EGF receptors are increased in many cultured epidermoid tumor cells. The increase in receptors has been associated with rearrangement and amplification of the EGF receptor gene in A431 cells. Since the observed changes in the EGF receptor and its gene may be related to the adaptation of epidermoid tumors to culture, we are studying whether the EGF receptor, its gene, and gene products are altered in biopsy specimens from human epidermoid tumors. EGF receptor levels will be quantitated with a competitive binding assay on fixed tissue sections of biopsy specimens using an EGF receptor specific monoclonal antibody, EGF-R1, to determine the frequency and the range of the EGF receptor levels in human epidermoid and nonepidermoid tumor biopsies. Receptor levels will be observed in hyperplastic and premalignant tissues obtained from skin and oropharyngeal biopsies to determine the point at which the receptor level begins to increase. Receptor levels will be observed by multiple biopsies in epidermoid tumors of the head and neck from treated patients to determine if the receptor content varies with therapy. Studies will determine whether the increased receptors detected by EGF-R1 binding are functional. Studies of the tumor receptor genome will determine the relationship of rearrangements and amplification. Studies of the receptor mRNA will determine if it is increased or modified. These studies will determine whether EGF receptors are increased in epidermoid malignancies and give insight into the molecular mechanism(s) which affect this observation. It may become apparent that epidermoid tumors and their premalignant states are an excellent system for determining the relationship of oncogenesis, gene regulation, and growth factors in vivo. (4)
