Primary brain lymphoma cell turnover differs in patients with and without AIDS: relationships to bcl-2 expression and host cell reaction.
Primary central nervous system lymphomas (PCNSLs) are more resistant to radiotherapy and chemotherapy in AIDS (A-PCNSLs) than in non-AIDS patients (NA-PCNSLs). We investigated 23 A-PCNSLs and 24 NA-PCNSLs. Lymphoma cell kinetics (i.e. proliferation [mitotic index, MIB-1 and PCNA labeling indices], apoptosis and turnover) were determined and compared with bcl-2 and LMP-1 expression, and to the percentage of tumor-infiltrating T-lymphocytes (T-TILs) and macrophages. A-PCNSLs showed lower proliferation (p < 0.005), less apoptosis (p < 0.0001) and slower cell-turnover (p < 0.0001) than NA-PCNSLs. LMP-1 was detected in 90% of A-PCNSLs and 5% of NA-PCNSLs, a finding correlating positively with bcl-2 expression (p < 0.0007). In contrast, T-TIL counts and CD4/CD8 T-TIL ratios were similar in A-PCNSLs and NA-PCNSLs. T-TIL counts correlated negatively with proliferation indices (from p < 0.05 to p < 0.0005) in NA-PCNSLs, but not in A-PCNSLs. Macrophage counts correlated positively with apoptosis in both groups. We concluded the following: (i) A-PCNSLs are characterized by accumulation of slow-cycling, long-lived cells that might be protected from apoptosis by LMP-1 induced bcl-2 expression, and independently from the host response; (ii) NA-PCNSLs are characterized by a faster cell turnover associated with an insufficient antiproliferative host response; and (iii) A-PCNSLs and NA-PCNSLs constitute 2 entities with distinctive morphology and different kinetic profiles that could account for different responses to therapy.
Christov
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Département de Pathologie, CHU Henri-Mondor, Université Paris XII-Val de Marne, Créteil, France.
Adle-Biassette
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Lechapt
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E
Poron
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Gray
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F
Gaulard
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P
Gherardi
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RK
D017209:Apoptosis; D001932:Brain Neoplasms / Q000473:pathology*; D002452:Cell Count; D002455:Cell Division; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008223:Lymphoma / Q000473:pathology*; D016483:Lymphoma, AIDS-Related / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism
C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral; D014763:Viral Matrix Proteins