Apoptosis and proliferative activity in thyroid tumors

To clarify the growth mechanisms of thyroid tumors, we examined apoptotic cells in 61 thyroid tumors, consisting of 14 adenomas, 35 papillary carcinomas, 4 follicular carcinomas, and 8 undifferentiated carcinomas, using terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate digoxigenin-nick end labeling (TUNEL). The proliferative activity was also evaluated immunohistochemically using the monoclonal antibody to Ki-67 antigen (MIB-1) in the same tumors. The apoptotic index (AI) was expressed as a percentage of the TUNEL-positive cells in the tumor cells, and a proliferation index (PI), being the percentage of Ki-67 positive cells, was calculated for each tumor. The overall level of AI was very low in all histotypes of the thyroid tumors analyzed, the mean AI being 0.5 +/- 0.4 in adenoma, 0.4 +/- 0.3 in differentiated carcinoma, and 1.8 +/- 1.5 in undifferentiated carcinoma. The PI in the thyroid tumor subtypes was significantly lower in adenoma and differentiated carcinoma, at 0.5 +/- 0.7 and 1.1 +/- 0.7, respectively, than that in undifferentiated carcinoma at 14.5 +/- 3.7 (P < 0.05). There was no correlation between clinicopathological factors and AI or PI in differentiated thyroid carcinoma. Our findings suggest that apoptosis occurs infrequently in thyroid tumors, and that proliferative activity markedly differs according to the thyroid tumor subtypes. Moreover, the ratio between proliferating cells and apoptotic cells may reflect thyroid tumor progression.