High Level of Glutathione- S -Transferase π Expression in Mantle Cell Lymphomas

PURPOSE: Prognosis of mantle cell lymphoma (MCL) remains poor. Patients who achieve a response to first line therapy usually relapse, and the probability of cure remains low. Glutathione-S-transferase pi (GST-pi) overexpression has been associated with alkylating agents and anthracycline resistance. GST-pi gene is located in 11q13 and is coamplified along with CCND1 gene in some human solid tumors. EXPERIMENTAL DESIGN: We performed immunohistochemical analysis of GST-pi expression in 24 consecutive MCLs, 12 follicular lymphomas (FLs), and 69 diffuse large B-cell lymphomas (DLBCLs). Cases were classified in three groups: high GST-pi expression (> 50% of cells were stained), moderate (5 to 50% cells were stained), or absent (< 5% cells were stained). GST-pi and CCND1 mRNA levels were also assessed by real-time reverse transcription-PCR analysis. RESULTS: All MCLs exhibit high GST-pi protein expression, compared with 29% of the DLBCLs and none of the FLs. MCLs expressed high levels of GST-pi and CCND1 mRNAs compared with DLBCLs and FLs. There was a strong relation between GST-pi and CCND1 mRNAs transcript levels in MCLs but not in DLBCLs. In conclusion, protein and mRNA GST-pi expression is high in MCL compared with FL and DLBCL. CONCLUSIONS: Overexpression of CCND1 in MCL is associated with a transcriptional up-regulation of the GST-pi gene. Our results suggest that the glutathione system could play a role in drug resistance in MCL.