CELL-PROLIFERATION, BCL-2, C-MYC, P53 AND APOPTOSIS AS INDICATORS OF DIFFERENT AGGRESSIVENESS IN SMALL LYMPHOCYTIC LYMPHOMA (SLL)

Cell proliferation activity, by MIB1 mAb, expression of bcl-2, c-myc a nd p53 gene proteins and apoptotic index (AI) were assessed in 54 case s of SLL and compared to the morphological subtypes of this disorder, defined by Lennert on the basis of amount and distribution of small an d larger activated lymphocytes as diffuse, tumor-forming and pseudofol licular subtypes (DS, TFS, PFS), MIB1 scores showed significant differ ences between DS, PFS and TFS (5.5%, 16.61% and 24.14%, respectively; p<0.0001). Worth noting, the MIB1. score did not differ significantly when comparing DS with the diffuse areas of PFS, or TFS with the pseud ofollicles of PFS, The mean bcl-2 gene protein score was displayed to a high extent in all subtypes but less extensively by larger activated lymphocytes that, conversely, expressed c-myc. MIB1 score correlated negatively with bcl-2 and positively with c-myc protein scores. These findings suggest that lymphocytes protected from apoptosis by bcl-2 wo uld be exponed to cell activation and growth acceleration provided by c-myc. This condition would account for a different aggressiveness of morphologically activated subtypes, such as TFS and PFS with larger ps eudofollicles, The survival analysis, performed in 23 cases, showed a trend of association of cell proliferation and c-myc expression with a more aggressive progression of the disease, Overexpression of p53 and apoptosis were found only in a minority of cases, unrelated to the su btypes, In conclusion cell growth fraction, bcl-2 and c-myc assessemen t may be of help in predicting the aggressiveness of different subtype s of SLL, This approach should be most conveniently applied to PFS, wh ich represents a continuum between DS and TFS, in order to distinguish , in this heterogeneous subtype, more indolent from more aggressive di sorders.