Survivin in relation to Bcl-2, Bax and in situ apoptotic cell death in anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive human malignancy. It is known that disturbances in apoptotic pathways have a great impact on tumor progression and aggressiveness. In this study the apoptosisrelated molecules Bcl-2 (antiapoptotic), Bax (proapoptotic) and survivin (an inhibitor of apoptosis) were analyzed immunohistochemically in thirty archival cases of ATC. In situ apoptotic cell death was analyzed by the TUNEL method. Mean Bcl-2 staining score (calculated from individual scores from 0-3) was low compared to those for Bax and survivin (p<0.05). High expression of survivin was associated with high Bax expression, and was significantly segregated from high Bcl-2 expressing cases (p<0.05). Despite high Bax expression, apoptotic cell death was low in the investigated carcinomas. In addition, the mean apoptotic index in high survivin expressing carcinomas was significantly lower than in low survivin expressing carcinomas (p<0.05). It could be concluded that down-regulation of Bcl-2 is counterbalanced by up-regulation of survivin, which may overcome the effects of high Bax expression, and, at least partly, explain the low apoptosis rate and high biological aggressiveness of ATC