In situ apoptosis in the thyroid

Recent evidence has emphasized the importance of programmed cell death, or apoptosis, in the maintenance of tissue homeostasis and pathogenesis of tum ors. This study analyzed the significance of apoptosis in relation to the e xpression of p53 and bcl-2 proteins, tissue proliferation defined by Ki-67 expression, and tissue histology in thyroid tissue. Extent of apoptosis was defined by morphological criteria and the terminal deoxynucleotidyl transf erase-mediated deoxy uridine triphosphate (dUTP) biotin nick end labeling ( TUNEL) assay. Immunocytochemistry was performed for p53, bcl-2, and Ki-67 e xpression. There was good correlation between TUNEL-reactive cells and morp hological evaluation criteria for apoptosis. The extent of apoptosis was si gnificantly associated with the type of thyroid lesion (r = 0.66990, p = 0. 000012), both proliferative (namely multinodular goiter) and neoplastic (be nign and malignant). A higher extent of apoptosis was evident in medullary and anaplastic carcinomas. Apoptosis also correlated to p53 protein accumul ation (r = 0.485, p = 0.00041) and Ki-67 immunoreactivity (r = 0.435, p = 0 .001). An inverse correlation was observed between bcl-2 expression and the extent of apoptosis (r = -0.33369, p = 0.01912). A direct correlation was also observed between p53 expression and Ki-67 immunoreactivity (r = 0.623, p = 0.0002). By inhibiting apoptosis, bcl-2, may cause a shift in tissue k inetics toward the preservation of genetically aberrant cells, thereby faci litating tumor progression. These results imply that rapidly proliferating tumors appear 50 have a high cell turnover state in which there may be incr eased chance of apoptosis among the proliferating cells. The ability of apo ptosis to occur in the presence of a possibly mutant p53 protein suggest th e existence of at least two p53 dependent apoptotic pathways, one requiring activation of specific target genes and the other independent of it. Howev er, keeping in mind the limited number of subjects studied in each subgroup and the rather low correlation coefficients, these possibilities would hav e to be substantiated in a larger study population.