Clinical drug-resistant nodular sclerosing Hodgkin's lymphoma is associated with decreased bcl-2 expression in the surrounding lymphocytes and with increased bcl-2 expression in the Reed-Sternberg cells

Identification of patients with Hodgkin's lymphoma who are primary refracto ry to chemotherapy will have great impact on treatment planning. Several st udies have indicated that up-regulation of the bcl-2 protooncogene expressi on in non-Hodgkin's lymphoma can cause resistance to chemotherapeutic drugs , For this reason we investigated the relationship between expression of bc l-2, the pro-apoptotic protein Bax and MIB-1 with clinical drug-resistance in Hodgkin's lymphoma Methods and results: Seven patients with nodular scle rosis Hodgkin's lymphoma under 40 years of age, who failed to achieve compl ete remission upon primary chemotherapy and 10 matched patients who did ach ieve complete response were selected from the Eindhoven Cancer Registry Tis sue sections from both groups of patients were stained for bcl-2, Bax and M IB-1, In the non-responding patients Reed-Sternberg cells expressed bcl-2 m ore frequently using a cut-off point of <25% to indicate negative cells (P = 0.04), whereas no differences were observed in the expression of Bax and MIB-1. In non-responding patients the lymphocytes surrounding Reed-Sternber g cells expressed bcl-2 less frequently (P = 0.002), using a cut-off point of <25%, whereas no difference was observed in the expression of Bax and MI B-1. Conclusion: A high percentage of Reed-Sternberg cells expressing bcl-2 prot ein and a low expression of bcl-2 protein in the surrounding lymphocytes is associated with treatment-failure, and subsequent poor survival in young p atients with nodular sclerosing Hodgkin's lymphoma. These results need furt her validation in larger studies.