Apoptosis and expression of apoptosis regulating proteins bcl-2, mcl-1, bcl-X, and bar in malignant mesothelioma

We investigated apoptosis and the expression of bcl-2, mcl-1, bcl-X, and ba s in histological sections from 35 malignant mesotheliomas and 21 metastati c adenocarcinomas. Moreover, the expression of bcl-2, mcl-1, bcl-X, and bas were assessed by Western blotting in nonmalignant human mesothelial cells (Met5A) and seven malignant cell lints, The apoptotic index in mesothelioma s was 1.07 +/- 1.14%. Patients with mesotheliomas showing a high apoptotic index (greater than or equal to 0.75%) had a worse prognosis (P = 0.008), b cl-2 positivity was observed in only seven cases, but bcl-X, mcl-1, and bar positivity was seen in all of them. In immunoblotting experiments, all mes othelioma cell lines were negative for bcl-2 but positive for bcl-X, mcl-1, and bar. The apoptotic index in bcl-2-negative mesotheliomas was 1.25 +/- 1.24% and in bcl-2-positive ones, 0.47 +/- 0.42% (P = 0.014), The apoptotic index did not significantly associate with bcl-X, mcl-1, or bar expression (P = 0.19, P = 0.25, and P = 0.46, respectively). No significant differenc e was observed in apoptosis or expression of bcl-2, bcl-X, or bar between m alignant mesotheliomas and metastatic adenocarcinomas. The former, however, showed more often weak mcl-1 immunoreactivity (P = 0.01), The results show that the extent of apoptosis may influence patient prognosis. bcl-2 is inv ersely associated with the apoptotic index but is relatively infrequently e xpressed in malignant mesotheliomas, Widespread expression of bcl-X, mcl-1, and bar suggests that these proteins may also take part in apoptosis regul ation in mesotheliomas.