A multivariate study of non Hodgkin's 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 kinetic studies seemed to differentiate distinctly between low grade lymphoma (n = 8, LI = 2.6%) compared to that of intermediate grade (n = 9, LI = 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 death (PCD) or apoptosis due to the overexpression of bcl-2 has been implicated as the possible pathogenesis for follicular lymphoma. We determined 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 understand 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 bcl-2 was present, except one. This study highlights some of the key biological features of NHL cells and their microenvironment.
Shetty
V
V
Rush Cancer Institute, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Mundle
S
S
Sanoy
A
A
Sanghvi
R
R
Loew
J
J
Marcus
B
B
Showel
J
J
Gregory
S
S
Raza
A
A
D017209:Apoptosis / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000627:therapeutic use; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D006801:Humans; D007065:Idoxuridine / Q000627:therapeutic use; D007150:Immunohistochemistry; D008228:Lymphoma, Non-Hodgkin / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D008264:Macrophages / Q000737:chemistry*; D015999:Multivariate Analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta / Q000032:analysis*
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta; D001973:Bromodeoxyuridine; D007065:Idoxuridine