Proliferative pattern of head and neck cancer

Tumor growth is primarily dependent on the fraction size of growing cells, their growth and proliferative rate, and the fractional cell death. In the present study, we focused specifically on the proliferative characteristics of squamous cell carcinomas of the head and neck region by using monoclonal antibodies and immunohistochemical methods. We studied two normally occurring antigens representative of cell proliferation: (1) ribonucleotide reductase, which is an independent cytoplasmatic enzyme and is intimately integrated in DNA synthesis, and (2) Ki-67, which is a nuclear antigen being expressed only in replicative cells. We also used intravenously injected bromodeoxyuridine (BRDU) for specific detection of tumor cells in the S phase of the cell cycle. In addition, in vivo injections of BRDU were also given to tumor-bearing mice to illustrate tumor cell kinetics by means of flow cytometry. The main observation was morphologic heterogeneity, with a high frequency of proliferative cell clusters in the cancer specimens interspersed among quiescent cells, which was demonstrated by the three monoclonal antibodies independent of each other. The experimental studies clearly visualized the transfer of BRDU throughout the tumor cell cycle. We conclude that immunohistochemical analysis provides valuable qualitative information on the proliferative pattern of tumor growth and, together with dynamic flow cytometry, may improve the clinical basis for individualized management of the cancer patient.