The overall goals of the project are to: a) study tumor cell kinetics in head and neck carcinomas using newly-developed monoclonal antibodies which identify proliferating cells in tissue sections and; b)develop a new classification system of head and neck tumors which integrates the slide-based cell kinetic information with traditional histologic and morphologic criteria. We hypothesize that this integrative tumor classification system will contain more accurate prognostic information than the present TNM/Stage I-IV system. A panel of currently available monoclonal antibodies which are specific for proliferating cells will be evaluated in frozen and fixed. Paraffin-embedded new and archival head and neck tumor specimens in order to systematically determine the fixation and immunostaining requirements of these antibodies. As none of the currently available proliferation-specific monoclonal antibodies can be used in formaldehyde-fixed, paraffin-embedded tissues, new proliferation-specific monoclonal antibodies capable of reacting with S-phase cells in archival formalin-fixed, paraffin-embedded tissue will be developed. Using immunocytochemical techniques with these antibodies and correlative flow cytometry, intratumor variations in cell kinetics in head and neck carcinomas will be studies. Prospective and retrospective studies of head and neck carcinomas and paraffin-embedded tumor specimens will be undertaken with the aim of correlating the cell kinetic data derived from immunocytochemical analysis of these tumors with such clinical endpoints as disease-free intervals, recurrences, metastases, survival. The applicant is presently a head and neck surgery fellow in the Dept. of Otolaryngology at the University of Washington. After completion of this two year clinical/research fellowship in July of 1988, the applicant will be joining the department as an assistant professor, as he intends to pursue an academic career with a firm commitment to both bench research and clinical surgical oncology. A ClDA would make it possible for the applicant to complete the training and background studies necessary for independent investigation while maintaining clinical skills which are central to his future plans. Furthermore, it would afford him the opportunity of working within the Pathology Dept. of the Univ. of Washington in which there are many other researchers working at the interface of clinical medicine and tumor biology.
