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P-glycoprotein expression in non-Hodgkin's lymphomas of human immunodeficiency virus infected patients
Paula Yurie Tanaka1, Edenilson Eduardo Calore
1Emilio Ribas Infectology Institute, Hematology Section, São Paulo, Brazil. pyt@uol.com.br <pyt@uol.com.br>
Abstract:
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.
Insights
P-glycoprotein (P-gp) expression in HIV-infected patients with non-Hodgkin's lymphoma indicates poor treatment response and survival. This finding highlights P-gp as a potential biomarker for predicting outcomes in this vulnerable population.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Multidrug resistance (MDR) poses a significant challenge in cancer therapy.
- P-glycoprotein (P-gp) is a key efflux pump implicated in MDR, reducing intracellular drug accumulation.
- The role of P-gp in non-Hodgkin's lymphoma (NHL), particularly AIDS-related lymphomas, requires further elucidation.
Purpose of the Study:
- To investigate the association between P-gp expression and treatment outcomes in HIV-infected patients with non-Hodgkin's lymphoma.
- To determine if P-gp expression predicts response to therapy and overall survival in this patient cohort.
Main Methods:
- Histologic samples from 45 HIV-infected non-Hodgkin's lymphoma patients without prior chemotherapy were analyzed.
- Immunohistochemical analysis using a monoclonal antibody specific for the MDR-1 isoform of P-gp was performed.
- Treatment response and survival data were correlated with P-gp expression status.
Main Results:
- P-gp expression was detected in 60% (27 out of 45) of the patient samples prior to treatment.
- Patients with positive P-gp expression showed significantly lower response to treatment (P=0.02) and overall survival (P=0.001).
- For patients achieving complete remission, the 3-year disease-free survival rate was 72.9%.
Conclusions:
- P-gp is expressed in non-Hodgkin's lymphoma of HIV patients before the initiation of treatment.
- P-gp expression is significantly associated with poor treatment response and reduced overall survival.
- P-gp may serve as a predictive biomarker for treatment outcomes in HIV-associated non-Hodgkin's lymphoma.
