Multidrug resistance (MDR-1) expression in AIDS-related lymphomas.
P-glycoprotein is a product of the multidrug resistance (MDR-1) gene. In non-Hodgkin's lymphoma, less than 20% of untreated de novo lymphomas express MDR-1 compared with approximately 50% after failure of chemotherapy. We wished to study the expression of MDR-1 in AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Tissue biopsies from 50 patients with newly diagnosed AIDS-NHL were studied by immunohistochemical analysis using C494, a monoclonal antibody specific for the MDR-1 isoform of P-gp. MDR-1 expression was correlated with patient demographics, lymphoma characteristics, response to chemotherapy, and survival. Forty-six males and four females with a median age of 38 years (range 26-63) were studied. A prior AIDS-defining opportunistic infection was reported in 35 patients (70%). The median CD4+ lymphocyte count was 69/mm(3) (range 0-920). Thirty-two patients (63%) had received prior anti-HIV therapy, including a protease inhibitor in five (10%). Pathologic types consisted of diffuse large cell in 13 (26%), immunoblastic in 13 (26%), small non-cleaved in 22 (44%), and high grade not otherwise specified in two (4%). The majority of patients (76%) had stage III/IV disease. Pre-treatment lymphoma tissues from 33 patients (66%) stained positively for MDR-1. MDR-1 positive patients had a significantly lower complete remission rate compared to MDR-1 negative patients (33 versus 65%, P=0.042). Duration of complete response was significantly longer in MDR-1 negative patients compared with MDR-1 positive patients (not reached versus 9.9 months, P=0.003). Strategies to overcome MDR-1 expression may be important for initial treatment in patients with AIDS-NHL.
Tulpule
Anil
A
Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. tulpule@hsc.usc.edu
Sherrod
Andy
A
Dharmapala
Dharshika
D
Young
Lillian L
LL
Espina
Byron M
BM
Sanchez
Maria Norilyn
MN
Gill
Parkash S
PS
Levine
Alexandra M
AM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000163:Acquired Immunodeficiency Syndrome / Q000401:mortality; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011241:Prednisone / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019380:Anti-HIV Agents; D009363:Neoplasm Proteins; D001761:Bleomycin; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D002955:Leucovorin; D011241:Prednisone; D008727:Methotrexate