Expression of apoptosis regulatory proteins of the Bcl-2 family and p53 inprimary resected non-small cell lung cancer

Proteins of the Bcl-2 family as well as p53 are important regulators of apo ptosis. Alterations in the expression of these proteins can contribute to t he formation of cancer, as well as influence tumour response to chemo- and radiotherapy. We used antibodies specific for the human Bcl-2, Mcl-1, Bar, Bak and p53 proteins to examine the expression of these apoptosis-regulatin g genes in 49 archival specimens of patients with radically resected non-sm all-cell lung cancer (NSCLC). Tumour cells containing immunostaining for th e antiapoptotic proteins Bcl-2 and Mcl-1 were present in 31% and 58% of the cases evaluated, respectively, whereas immunopositivity for the proapoptot ic proteins Bar and Bak was found in 47% and 58% of the samples. p53 immuno positivity was detected in 61% of the samples. The expression of Bcl-2 and p53 and the expression of Mcl-1. and Bar showed a positive association (P = 0.02 and P = 0.06 respectively), whereas the expression of Bar was inverse ly related to p53 (P = 0.008). The expression of Bcl-2 had a negative influ ence on relapse-free survival in this population of primary resected NSCLC patients (P = 0.02). The expression of 953 and Bcl-2 was significantly asso ciated with metastasis-free survival (P < 0.01). Only patients with p53-pos itive tumours developed metastases during the follow-up period. Our results establish the frequent expression of the Bcl-2 family proteins Bcl-2, Mcl- 1, Bar and Bak in NSCLC. It can be expected that Bcl-2 family members have no straightforward impact on clinical outcome in this disease because their interactions in the regulation of apoptosis are complex.