Bcl-2, Bax and p53 Expression in Rectal Adenocarcinoma. Correlation with Classic Pathologic Prognostic Factors and Patients' Outcome

Abstract

Background: Bcl-2 oncoprotein inhibits apoptosis, whereas bax protein promotes apoptosis by enhancing cell susceptibility to apoptotic stimuli. This study examined the bcl-2, bax and p53 expression in rectal adenocarcinomas and their relationship with tumor prognosis. Patients and Methods: Paraffin-embedded 4-μm tumor sections obtained from patients with rectal adenocarcinoma who underwent colectomy for therapeutic reasons, were analyzed with a standard streptavidin biotin peroxidase method, using polyclonal and monoclonal antibodies. Patients were followed up for 1.5-83 (mean±SD: 47.19±6.2) months. Results: Positive immunoreactivity for bcl-2, bax and p53 was detected in 21 (37%), 28 (50%) and 45 (80%) tumors, respectively. Bax was co-expressed in 17 out of 21 bcl-2(+) cases, whereas p53 was co-expressed in 18 out of 21 bcl-2(+) and 17 out of 28 bax(+) cases. Loss of bax expression was associated with advanced stage and high grade tumors (p<0.01). Local (n=6) or distant (n=5) tumor recurrence was established in 11 cases. All these cases were bax(+), bcl-2(-) and p53(+). Bax and p53 expressions were correlated with adverse outcome (p<0.05) while bcl-2 presence did not influence survival. Bcl-2(-)/bax(+)/p53(+) cases showed lower survival than bax(+)/bcl-2(+)/p53(+)cases (p<0.001). Conclusion: In rectal adenocarcinoma, bax and bcl-2 proteins co-express frequently with p53. Co-expression of bax with p53 protein is associated with poor clinical outcome, especially in cases without concomitant expression of bcl-2.