A MULTIVARIATE STUDY OF NON-HODGKINS-LYMPHOMA INVOLVING PROLIFERATION, APOPTOSIS, BCL-2 AND THE MICROENVIRONMENT

The study was carried out on 22 patients with non-Hodgkin's lymphoma ( NHL) who had received sequential infusions of two thymidine analogues iododeoxyuridine (IUdR) and bromodeoxyuridine (BrdU). Cell cycle kinet ic studies seemed to differentiate distinctly between low grade lympho ma (n = 8, LI = 2.6%) compared to that of intermediate grade (n = 9, L I = 13%, p = 0.0001) and high grade NHL (n = 5, LI = 16.3%, p = 0.0062 ). While the majority of 14 intermediate and high grade lymphomas had a high labeling index there were 3/14 patients with a LI of 5.5%, 5.5% and 4,1% respectively. A decrease in the rate of programmed cell deat h (PCD) or apoptosis due to the overexpression of bcl-2 has been impli cated as the possible pathogenesis for follicular lymphoma. We determi ned the presence of bcl-2 protein immunohistochemically and apoptosis by in situ end labeling of DNA which detects cells in early stages of PCD not recognized morphologically. Nine NHL patients demonstrated PCD ranging from 1%-40%, while it was undetectable in 13/22 patients. Of these 13 cases, 6 showed the presence of bcl-2 expression. To understa nd the relationship of the microenvironment to the lymphoma cells, the presence of transforming growth factor beta (TGF-beta) was determined immunohistochemically. TGF-beta was present in all the cases where bc l-2 was present, except one. This study highlights some of the key bio logical features of NHL cells and their microenvironment.