PROLIFERATIVE CHARACTERISTICS OF HEAD AND NECK TUMORS - IN-VIVO EVALUATION BY BROMODEOXYURIDINE INCORPORATION AND FLOW-CYTOMETRY

Cell proliferation of head and neck cancers was studied in 52 patients using in vivo bromodeoxyuridine (BUDR) incorporation. Patients received 250 mg BUDR intravenously several hours prior to biopsy of the tumor tissue. Bivariate flow cytometry was used and enabled us to rapidly obtain DNA ploidy, labelling index (LI), DNA synthesis time (TS) and tumor potential doubling time (Tpot). This method was found to be suitable to obtain complete cytokinetic data in 46/52 (88.5%) patients. The mean BUDR LI was 7.9% (range 2-18%); mean TS was 11.6 h (range 6-28.5 h); mean Tpot was 5.7 days (range 2-30 days). BUDR LI and TS were significantly correlated with histological differentiation grading: G(3) tumors showed higher LI values and shorter TS values than G(1)/G(2) tumors. A similar correlation was found between LI or TS and tumor dimensions. Tpot was also significantly lower in larger tumors, such as in those with a higher grading. No significant correlation was found between LI or TS and DNA ploidy (50% of the tumors in our series were DNA aneuploid), while Tpot was found to be 10 days in diploid tumors, compared to only 6.3 days for the aneuploid tumors (p < 0.05). All cases with documented lymph node involvement (N+) showed significantly higher LI, and shorter TS and Tpot values if related to nodal free ones (Tpot = 10 days in N+ patients and 6.3 days in N- patients; p < 0.05). The results of this study suggest that the method employed is clinically feasible and could be a useful aid in defining the prognosis of head and neck cancer patients. Since cell kinetic information is readily available using this method, it could be incorporated into clinical trials to improve the design of therapeutic strategies for cancer patients.