Apoptosis and expression of the proto-oncogenes bcl-2 and p53 and the proliferation factor Ki-67 in human medullary thyroid carcinoma

Apoptosis and immunoreactivity for bcl-2, p53, and Ki-67 were studied in 21 patients with medullary thyroid carcinoma (MTC). The DNA nick end labeling method was used to assess apoptosis. The relationships between the different factors were analyzed, as were their relations to clinicopathological data, including survival. More than 80% of the tumors harbored apoptotic cells. Tumors in individuals who had died of the MTC disease had a higher percentage of apoptosis. All cases demonstrated immunoreactivity to bcl-2; disease-free individuals had a higher rate than those with recurrent disease. No obvious pattern could be discerned in the relation of p53 or Ki-67 to the outcome of the MTC disease. An inverse correlation between bcl-2 and apoptosis (r = -0.81; p < 0.01) was demonstrated. bcl-2 was significantly (p = 0.014) associated with apoptosis even after taking both p53 and Ki-67 into consideration, but these two factors were unrelated to apoptosis. None of the factors studied were correlated to crude survival, either in univariate or in multivariate analyses. This study established that bcl-2 immunoreactivity is closely associated with apoptosis in MIG, suggesting that a downregulation of the bcl-2 protein is related to a more aggressive growth rate and might be a useful marker for the evaluation of MTC.