BCL-2 EXPRESSION IN PLASMA-CELLS FROM NEOPLASTIC GAMMOPATHIES AND REACTIVE PLASMACYTOSIS - A COMPARATIVE-STUDY

Background and Objective. bcl-2 oncoprotein plays a major physiologica l role in hemopoietic and non- hemopoietic cells by preventing apoptos is (programmed cell death). Disregulatlon of this process may be impor tant in oncogenesis and the response to treatment of patients with dif ferent hematological malignancies. We have investigated the levels of bcl-2 expression in plasma cells from patients with reactive plasmacyt osis (RP), monoclonal gammopathy of unknown significance (MGUS) and mu ltiple myeloma (MM), correlating the bcl-2 expression and clinico-biol ogical features in MM patients. Design and Methods. The percentage of bcl-2 (+) plasma cells and levels of bcl-2 protein expression were inv estigated in 73 patients at diagnosis. Immunofluorescence and immunoen zymatic methods were applied using McAb against bcl-2 protein, and the intensity of protein expression was assessed by both the mean channel fluorescence intensity (MFI) and semiquantitative methods. To evaluat e the intensity of bcl-2 expression in proliferating plasma cells, seq uential double immunoenzymatic staining with McAb Ki-67 and bcl-2 was applied in 10 patients with MM. Correlations between bcl-2 expression and the clinico-biological features in MM patients were also studied. Results. The proportion of bcl-2 (+) plasma cells was significantly hi gher in MGUS and MM than in RP (p < 0.001). The intensity of bcl-2 exp ression in plasma cells (assessed by MFI) was significantly different between all groups studied (p < 0.0001). RP showed lower expression th an MGUS and MM patients, MM stage III patients demonstrated higher bcl -2 expression values than MGUS (p < 0.01). According to the proportion of plasma cells expressing hi-CT, patients with a proliferative index (Ki-67(+)) > 4% showed tower bcl-2 expression than patients with prol iferative index < 4% (p < 0.05). Immunocytochemistry showed that plasm a cells from RP had a lower intensity of bcl-2 expression than MM (p < 0.001), and double immunostaining Ki-67/bcl-2 demonstrated that the m ajority of proliferating plasma cells had weak bcl-2 expression. There was no correlation between bcl-2 expression and clinico-biological pa rameters, response to therapy or overall survival in MM patients. Inte rpretation and Conclusions. Globally, the number of bcl-2 (+) plasma c ells and the intensity of protein expression in neoplastic gammopathie s are significantly higher than in reactive plasmacytosis and bcl-2 le vels tend to increase with disease stage. bcl-2 may be relevant to the pathogenesis of malignant gammopathies, prolonging the survival of pl asma cells by preventing apoptosis and increasing the chance of acquir ing additional gene defects. bcl-2 expression could also contribute to the resistance to chemotherapy observed in MM disease. (C) 1998, Ferr ata Storti Foundation.