The Concept of Phenotypic Deviation: A Multiparameter Approach for Biologic Prognostic Markers in FL
Z Peerwani, P Elson, J Diacovo, A Banham, J Cook, B Pohlman, ED Hsi. Cleveland Clinic, Cleveland, OH; University of Oxford, Oxford, United Kingdom
Background: Follicular lymphoma (FL) generally has an indolent clinical behavior. However, there is great heterogeneity in an individual patient's course. Thus, there is interest in discovering biologic markers that might yield additional prognostic and pathobiologic insight. Prior studies demonstrate heterogeneity in markers such as CD10, BCL2, FOXP1, and MUM1. We hypothesized that deviation of FL cells from a prototypical phenotype (PP) might identify patients with poor clinical outcome.
Design: Cases of newly diagnosed FL (grade 1-3a) biopsied between 9/1/85 and 12/31/2002 were studied for expression of CD10, BCL2, FOXP1, and MUM1 by immunohistochemistry (IHC) in a tissue microarray (TMA). BCL2 and MUM1 were scored positive if >20% of FL cells stained positively and CD10 was positive if >10% of cells stained positively. For FOXP1, positivity was defined as intense staining in the majority of cells. A PP based on a germinal center B-cell (CD10+, MUM1- and FOXP1-) or FL cell (BCL2+) was defined as CD10+/MUM1-/FOXP1-/BCL2+. The number of phenotypic abnormalities (PA, 0-4) were scored for each case and correlated with overall survival (OS). The number of CD68+ extra-follicular lymphoma-associated macrophages (ef-LAM) was reported previously. OS and FL prognostic index (FLIPI) were determined by chart review.
Results: 61 patients had complete data for analysis. 54% of patients were male with a median age of 57 years (range 24-83). The median follow-up was 10.6 years (range 6.0-19.7 years). Based on FLIPI score, 35% of patients were low risk, 23% intermediate risk, and 42% high risk. 11% of cases were CD10-, 17% BCL2-, 69% FOXP1+, and 26% MUM1+. On univariate analysis, CD10-, BCL2-, >1 PA, >16.8 ef-LAM, and high FLIPI were associated with shorter OS (p≤.05 for each). On multivariate analysis, only >16.8 ef-LAM (HR 2.32, 95%CI 1.07-5.05, p=.03) and >1 PA retained significance (HR 2.15, 95%CI 1.21-3.82, p=.009) and were independently associated with shorter OS. Adjusting for PA and ef-LAM, FLIPI was not an independent predictor.
Conclusions: Heterogeneity in expression of CD10, BCL2, FOXP1, and MUM1 exists in FL and the concept of deviation from the PP appears to have prognostic importance in FL. These data suggest that features of both the tumor cells and the microenvironment appear to be independent predictors of outcome in FL and future multiparameter studies should evaluate both components.
Monday, March 22, 2010 1:00 PM
Poster Session II # 160, Monday Afternoon