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Molecular Oncology, Markers, Clinical Correlates |
Expression in Mantle Cell Lymphomas
1 Département de Biologie Clinique, Laboratoire d’Hématologie, 2 Département d’Anatomie Pathologie, 3 Département de Biostatistique, and 4 Département de Médecine, Institut Gustave Roussy, Villejuif, France, and 5 Service d’Hématologie and 6 Service d’Anatomopathologie, Hôpital Necker, Paris, France
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 
(GST-) overexpression has been associated with alkylating agents and anthracycline resistance. GST- 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- 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- expression (> 50% of cells were stained), moderate (5 to 50% cells were stained), or absent (< 5% cells were stained). GST- and CCND1 mRNA levels were also assessed by real-time reverse transcription-PCR analysis.
Results: All MCLs exhibit high GST- protein expression, compared with 29% of the DLBCLs and none of the FLs. MCLs expressed high levels of GST- and CCND1 mRNAs compared with DLBCLs and FLs. There was a strong relation between GST- and CCND1 mRNAs transcript levels in MCLs but not in DLBCLs. In conclusion, protein and mRNA GST- 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- gene. Our results suggest that the glutathione system could play a role in drug resistance in MCL.
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