Clinical Significance of Bcl-2 and Ki67 Protein Expression in Agrressive Non-Hodgkin Lymphoma.

Abstract

Aggressive Non-Hodgkin lymphoma (NHL) is heterogeneous group with respect to clinical, histopatological and evaluative features. The International Prognostic Index (IPI) has provided a widely accepted prognostic set of criteria to design therapy. However, IPI dose not determine whether routine phenotypic features, beside IPI, may influence survival. We evaluate the prognostic significance of Bcl-2 and Ki67 protein expression in relation to clinical presentation and outcome. In the period 1989–2002,two hundred eleven patients with newly diagnosed aggressive NHL were recorded in our Department. In this study we included patients with available biopsy sample. Protein expression was analyzed on paraffin embedded tumor tissue by imunohistochemistry in relation to clinical factor and outcome. The expression of more than 20% of neoplastic cell was considered positive for bcl-2, and more than 60% for Ki-67. Comparison was made by x2 test. Survival curves were considered by Kaplan-Meyer method and compared by the long-rank test. Sixty seven patients were recorded and their characteristic were: median age 53 years, stage III and IV, 67%; present B symptoms 44%,; bone marrow infiltration 29%, elevated LDH 58%, performas status more then 1– 26%; extra nodal sites more than 2 –34%. All 62 patients received antracyclin based combination chemotherapy, 72% CHOP regiment. Overall survival was 52% with a follow up 6–183 months. Bcl-2 expression was observed in 35,5% (22pts) and Ki67 positivity over 60% in 20 pts (30%). Overall survival was influenced by bcl-2 and Kli67 expression. Bcl-2 positive cases were significantly associated with lower overall survival (20% vs. 58%; p<0.01). Overall survuval was significantly worse in patients with Ki67 positivity over 60% (27% vs. 49%; p<0.05) Bcl-2 and Ki67 monoclonal antibody immunostaging appears to be a simple and reproducible method of determining biological potential of tumor cells and provides useful prognostic information in patients with aggressive NHL.