1. ¹Département de Médecine, Institut Gustave Roussy, Villejuif, France
2. ²Département de Biostatistique, Institut Gustave Roussy, Villejuif, France
3. ³Département de Pathologie, Institut Gustave Roussy, Villejuif, France

Correspondence: Dr V Ribrag, Département de Médecine, Institut Gustave-Roussy, 39 Rue C Desmoulins, Villejuif 94805, France. Fax: +33 1 42 11 52 71

⁴JB and PF equally contributed as last authors to this work

Received 18 April 2002; Accepted 15 January 2003.

Abstract

Among mechanisms potentially involved in resistance to alkylating agents and anthracyclines, the glutathione system has been extensively studied in vitro. We analyzed by immunohistochemistry the relation between glutathione s-transferase (GST-) expression in tumor cells and outcome in 69 cases of diffuse large B-cell NHL (DLBCL). GST- expression was considered as low when <50% of tumor cells were stained and high when 50% tumor cells were stained. Median follow-up was 58 months. GST- expression was correlated with the probability of achieving complete remission (CR). Patients with high GST- expression had a worse 5-year freedom from progression (FFP). High GST- expression was associated with a trend for lower survival. In the group of patients with International Prognostic Index (IPI) 0–1, low GST- expression was associated with a CR rate of 88%, a 5-year FFP of 7620% and a 5-year survival of 7816% compared to 36, 1416 and 4032%, respectively, in patients with a high GST- expression (P=0.002, P<10^-5 and P=0.01, respectively). No correlation was found between GST- expression and lactico deshydrogenase serum level, age, Ann Arbor stage, performance status, and IPI index. Both GST- expression and the IPI index correlated with FFP. After incorporating IPI and GST- expression in a multivariate analysis for FFP, GST-p expression remained the only prognostic factor (P=0.003). Our findings suggest that GST- expression had strong prognostic significance in DLBCL, which appears to be independent of other prognostic parameters in those disorders.