Evaluation of apoptosis and immunohistochemical expression of the apoptosis-related proteins in mesothelioma.

We evaluated apoptosis and the expression of apoptosis-related proteins in 3 mesothelioma cell lines and 34 paraffin-embedded tissue specimens. Apoptosis was evaluated by the TUNEL method, while expression of the apoptosis-related proteins, bax, bcl-2, survivin, caspase-3 and cleaved caspase-3 was evaluated by immunohistochemical staining. The mean apoptotic index of mesothelioma tissue was 17.6 (ranging from 0 to 41.9), which was significantly lower than that of other carcinomas. Thirty-one of 34 cases showed caspase-3 expression. However, the cleaved caspase-3 index in mesothelioma was only 14.7 (ranging from 0 to 36.5). There was a direct correlation between apoptotic index and cleaved caspase-3 index (p value = 0.03). All cases of mesothelioma tissue showed bax expression, while only 2 cases showed bcl-2 expression. Thirty of 31 mesothelioma cases showed cytoplasmic expression of survivin, and 16 cases out of 30 cases showed diffuse staining while 11 cases showed strong staining. Three mesothelioma cell lines also showed high cytoplasmic expression of bax, caspase-3 and survivin, while there was no expression of bcl-2, and apoptosis and cytoplasmic expression of cleaved caspase-3 were limited. mRNA expression of survivin was confirmed by RT-PCR and its protein was confirmed by western blotting. In conclusion, apoptosis is an uncommon event in mesothelioma and low mean cleaved caspase-3 index, suggesting the role of low activation of caspase-3 for inhibition of apoptosis. High expression of survivin in mesothelioma may play a role in inhibition of apoptosis.