Cell of Origin Subtype Determined by Immunohistochemistry and MYC and BCL2 Dual Expression in DLBCL as Potential Prognostic Indicators
Angela MB Collie, Brian T Hill, Eric D Hsi. Cleveland Clinic, Cleveland, OH
Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease entity with multiple subtypes determined by various methods. Recent work has focused on multiple factors, including MYC and BCL2 expression as well as cell of origin (COO) molecular subtype, as potential prognostic indicators. COO studies have shown that the non-germinal center B-cell-like subtype (NGC) has a worse prognosis than the germinal center B-cell like subtype (GCB) in some studies. In addition, a recent study demonstrated that dual MYC expression and BCL2 expression indicated a worse prognosis. We evaluated expression of MYC, BCL2, and COO subtype by immunohistochemistry (IHC) in a cohort of uniformly treated de novo DLBCL cases at our institution.
Design: 97 cases of de novo DLBCL treated with R-CHOP were identified, and a tissue microarray was created. Survival data and treatment type were collected for these patients. COO subtype was determined by IHC using the Hans, Choi and Tally algorithms in all cases and confirmed by gene expression profiling in a subset of cases. BCL2 and MYC IHC was also performed on 84 cases. A threshold of 50% expression for BCL2 and 40% expression for MYC was defined as positive.
Results: COO subtype determined by IHC was prognostic with the NGC subtype having a significantly shorter overall survival (OS) compared to the GCB subtype with the Choi (p=0.03), Hans (p=0.01) and Tally algorithms (p=0.007). 36 cases were positive for MYC (36%) while 49 cases were positive for BCL2 (49%). High BCL2 expression was correlated with the NGC subtype. 21 cases of dual MYC and BCL2 expression were identified (25%). High dual positivity for MYC and BCL2 was associated with a trend in worse survival while neither MYC nor BCL2 expression was associated with a difference in OS. When analyzed in the NGC and GCB subtypes, dual MYC and BCL2 expression was not prognostic.
Conclusions: Identification of prognostic markers in DLBCL is essential for the stratification of patients for treatment strategies and clinical trials. The current study confirms that determination of COO subtype by IHC predicts OS using three published algorithms. In addition, this data emphasizes a potential role for MYC and BCL2 IHC in DLBCL prognostication.
Monday, March 4, 2013 1:00 PM
Poster Session II # 199, Monday Afternoon