P-glycoprotein expression in non-Hodgkin's lymphomas of human immunodeficiency virus infected patients.
Multidrug resistance (MDR) is a challenge in cancer treatment. One of the most studied mechanisms is P-glycoprotein (P-gp), which acts as a drug efflux pump, with decreased intracellular accumulation of drugs. It still needs to be clarified whether P-gp expression has a significant impact on non-Hodgkin's lymphoma treatment response, but a poor outcome has been reported in patients with positive P-gp expression. AIDS-related lymphomas have aggressive behavior, and although a complete response could be achieved, relapse is not uncommon. In an attempt to determine a possible relationship between MDR and poor outcome in this population, histologic samples obtained from 45 non-Hodgkin's lymphoma HIV-infected patients without previous cytotoxic therapy were submitted to immunohistochemical analysis using monoclonal antibody C494 specific for the MDR-1 isoform of P-gp. Samples from 27 patients (60%) were positive. Response to treatment (P=0.02) and overall survival (P=0.001) were significantly lower in patients with positive P-gp expression. In patients having achieved complete remission, the median disease-free survival (DFS) was not reached; the mean DFS was 57.2 months with DFS rates of 72.9% in three years. Our results show that P-gp is expressed before treatment of non-Hodgkin's lymphoma of HIV patients, and is related to poor response to treatment and overall survival.
Tanaka
Paula Yurie
PY
Emilio Ribas Infectology Institute, Hematology Section, São Paulo, Brazil. pyt@uol.com.br <pyt@uol.com.br>
Calore
Edenilson Eduardo
EE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000401:mortality; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000401:mortality; D014408:Biomarkers, Tumor / Q000378:metabolism; D002452:Cell Count; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate; D014750:Vincristine / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019380:Anti-HIV Agents; D014408:Biomarkers, Tumor; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone