The Stromal Marker Sparc Predicts Survival of Patients with Diffuse Large B-Cell Lymphoma Treated with Rituximab
PM Meyer, LM Smith, K Fu, TC Greiner, P Aoun, J Delabie, RD Gascoyne, A Rosenwald, RM Braziel, E Campo, JM Vose, G Lenz, LM Staudt, WC Chan, DD Weisenburger. University of Nebraska Medical Center, Omaha, NE; Leukemia/Lymphoma Molecular Profiling Project, Omaha, NE
Background: Patients with diffuse large B-cell lymphoma (DLBCL) have wide variation in survival, with tumors derived from germinal center B-cells (GCB) having better survival than those from activated B-cells (ABC). We have recently reported the ability of stromal signatures to predict prognosis in DLBCL. Our goal was to evaluate whether immunohistochemical stains for two stromal cell (SC) markers, CD68 and SPARC, predict survival in DLBCL.
Design: Tissue microarrays (TMA) were created from 216 cases of DLBCL treated with rituximab in combination with CHOP-like therapies. Initial clinical and follow-up data was available for all 216 cases. TMA were analyzed for CD10, BCL6, MUM1, CD68, and SPARC by immunohistochemistry. Gene expression profiling (GEP) was available for 168 of these cases. DLBCL were divided into two groups: with “high” numbers of SC (>15% of total cells positive for SPARC; >20% of total cells positive for CD68) or “low” SC content. DLBCL were divided into GCB or ABC types by either GEP or the Hans immunohistochemical algorithm. Chi-square test was used to compare patient characteristics and SC numbers. Overall survival was determined by Kaplan-Meier method, with differences evaluated by log-rank test. Multivariate analysis of survival predictors was performed by Cox regression.
Results: When using SPARC, patients with DLBCL with high SC content had a significantly longer overall survival than those with low SC content. The presence of B symptoms was associated with low SC content. After adjusting for the International Prognostic Index (IPI) and cell of origin, DLBCL with low SC content had a 3.4 fold increased risk of death compared to those with high SC content. When subtypes of DLBCL were examined, SC content did not have prognostic value in GCB type DLBCL; however, ABC type DLBCL with high SC content had a significantly longer overall survival than those with low SC content. When using CD68, the SC content did not have prognostic value in all DLBCL or the subtypes of DLBCL.
Conclusions: Our results show that patients with DLBCL with high SC content, as determined by SPARC immunohistochemistry, have longer overall survival than those with low SC content. This difference is likely due to the markedly better overall survival observed in ABC type DLBCL with high SC content.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 187, Wednesday Morning