PRAME Expression in Follicular Lymphoma (FL) and Diffuse Large B Cell Lymphoma (DLBCL)
M Perez, JA Shafer, C Curry, Y Zu, A Ewton, G Dotti, C Chang. The Methodist Hospital, Houston, TX; Baylor College of Medicine, Houston, TX
Background: Preferentially expressed antigen of Melanoma (PRAME) is a cancer-testis antigen over expressed in many types of solid tumors and leukemia. The importance of this antigen is its immunogenic properties and sparse expression in normal tissues. It therefore has the potential use as a marker of minimal residual disease and as a target for immunotherapy. We have recently demonstrated our ability to generate PRAME specific cytotoxic T lymphocytes that can kill PRAME positive blasts in chronic myelogenous leukemia (Quintarelli et al Blood 2008). To further evaluate the potential use of this novel therapeutic approach to treat lymphomas, we evaluated PRAME expression in FL and DLBCL, the two most common types of non-Hodgkin's lymphoma.
Design: Tissue microarray (TMA) blocks were constructed from 66 archived cases of de novo DLBCL and 31 de novo cases of FL, each case consisting of three 1.2 mm core sections. IHC staining with commercially acquired PRAME antibody (Abcam) was performed on TMAs. Cases were classified as positive or negative for cytoplasmic and/or membrane staining based on >20% of cells showing expression.
Results: Normal lymphocytes did not express the PRAME antigen based on the negative control on the DLBCL TMA. DLBCL cases negative for the PRAME antigen demonstrated a positive background control in endothelial cells. Thirty seven cases (56%) of DLBCL stained positive for the PRAME antigen. However, the expression of PRAME in DLBCL did not correlate with germinal-center or activated B-cell type of DLCBL (based on the expression of immunohistochemical markers of BCL-6, CD10 and MUM1), with high or low IPI scores, or with nodal or extranodal disease. Furthermore, no significant correlation with overall survival was identified. For FL, 24 cases (77%) of FL showed PRAME expression: Grade I (10/12), Grade II (7/10), and Grade III (7/9).
Conclusions: IHC, with PRAME antibody, demonstrated that a substantial percentage of FL and DLBCL cases expressed this cancer-testis antigen. This suggests that the PRAME antigen may be a possible target for immunotherapy with our recently developed technology for subsets of FL and DLBCL cases expressing PRAME. Additionally, PRAME may serve as a marker for minimal residual disease using real-time quantitative RT-PCR for these lymphoma cases. However, PRAME expression cases did not provide significant risk stratification data for clinical outcome in our cohort of DLBCL cases.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 147, Tuesday Morning