Correlation of MYC Gene Translocation Status with MYC Protein Expression in Burkitt Lymphoma and Diffuse Large B Cell Lymphoma
Ewa B Bajor-Dattilo, Alina Leung, Kieron Dunleavy, Svetlana Pack, Diane Arthur, Mark Raffeld, Wyndham Wilson, Elaine S Jaffe, Stefania Pittaluga. NIH, Bethesda, MD
Background: MYC proto-oncogene is rearranged in several aggressive B cell lymphomas, including Burkitt Lymphoma (BL) and Diffuse Large B cell Lymphoma (DLBCL). In cases of BL, MYC translocation to immunoglobulin (IG) gene loci is seen in 100% of cases and it represents a primary event. In contrast, only 8 – 10% of DLBCL show MYC translocation, often to non-IG partners, and usually within a complex karyotype, suggesting it is a secondary event. MYC translocation correlates with inferior survival in patients who concomitantly have BCL-2 translocation. This study tested whether MYC expression by immunohistochemistry (IHC) can predict MYC translocation and be used as a prognostic IHC marker.
Design: 41 HIV+ DLBCL, 76 HIV- DLBCL, 12 HIV+ BL and 19 HIV- BL patients were enrolled in a clinical trial. Of these cases, there was archival material sufficient to perform additional interpretable studies in 19 HIV+ DLBCL, 30 HIV- DLBCL, 7 HIV+ BL and 7 HIV- BL cases. FISH and IHC were performed using Vysis LSI MYC break apart probe and MYC antibody (clone Y69, Epitomics). IHC slides were scored based on stain intensity and percent positive cells and results were correlated with presence of MYC translocation.
Results: All BL cases, regardless of HIV status (14 of 14), had MYC translocation which correlated with strong (2-3+/3) MYC expression in 75-100% of cells. In contrast, 14% of HIV- DLBCL (4 of 30) and 21% of HIV+ DLBCL (4 of 19) showed MYC translocation while 63% of HIV- DLBCL (19 of 30) and 84% of HIV+ DLBCL (16 of 19) showed MYC expression. In addition, both within translocation positive and translocation negative cases of DLBCL, irrespective of HIV status, there was a wide range of expression of MYC, from no expression at all (0/3) to strong expression (2-3+/3) in 75-100% of cells.
Conclusions: The above data demonstrates that although strong MYC expression correlates with MYC translocation in BL cases, strong MYC expression by IHC is not predictive of MYC translocation status in DLBCL. In addition, this data suggests that a mechanism other than MYC translocation is responsible for MYC expression in a large fraction of DLBCL patients.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 177, Tuesday Afternoon