Bax protein expression in colorectal cancer: Association with p53, bcl-2 and patterns of relapse

This study evaluated the frequency and the prognostic significance of bax, bcl-2 and p53 proteins in stage B and C adenocarcinomas of the colon and re ctum. Paraffin-embedded specimens from 268 patients with colorectal adenoca rcinomas, treated with surgery, were assessed; of these 160 cases wet-e Duk e's stage B and 108 cases were Duke's stage C disease. Adjuvant chemotherap y was given to all stage C and to 108 out of 160 stage B cancer patients, w hile those having rectal malignancy also received pelvic radiotherapy. Duke 's stage B patients were treated either with surgery alone or with surgery and radiotherapy. The follow-up period at the time of analysis ranged from 12-72 months (median 32 months). Immunohistochemical expression of bax, bcl -2 and mutant p53 proteins was detected with a frequency of 42%, 37% and 48 %, respectively. However, the expression was strong only in 17% of tumours, on average. A strong bcl-2 expression was significantly associated with a strong bax expression (p < 0.0001) and with absence of p53 nuclear accumula tion (p < 0.005). There was, however; no correlation between box and p53 pr oteins. Furthermore, bcl-2 expression was significantly more frequently gra de 1 and 2 adenocarcinomas compared to grade 3 disease (p = 0.01). In stage B (but not C) adenocarcinomas, bax expression was directly associated with higher risk of local relapse (p = 0.04). By contrast, cases with p53 nucle ar accumulation, when they had received adjuvant radiotherapy, Mia e signif icantly associated with a lower incidence of local relapse (p = 0.01) but a higher rate of distant metastasis (p = 0.06). Multivariate analysis for di sease free and overall survival showed that bax expression and high Duke's stage were independent prognostic parameters associated with an unfavourabl e outcome (p = 0.009 and p = 0.0001, respectively). It was concluded that t he immunohistochemical expression of bax is a marker of poor prognosis and of a higher risk of local relapse in patients with colorectal adenocarcinom as. p53 nuclear accumulation is associated with a better local control foll owing radiotherapy and with a metastatic phenotype. The development of nove l monoclonal antibodies recognising specifically the mutated versus the wil d type form of proteins would apparently improve the prognostic and predict ive value of the immunohistochemically detected apoptotic proteins.