BCL2 and MYC Protein Expression in Primary Testicular Diffuse Large B Cell Lymphoma
Randy D Gascoyne, King L Tan, Susana Ben-Neriah, Kerry J Savage, David Telio, Tawny Hung, Joseph M Connors, David W Scott, Christian Steidl, Graham W Slack. British Columbia Cancer Agency, Vancouver, Canada
Background: Concurrent MYC and BCL2 gene rearrangements by FISH in diffuse large B-cell lymphoma is associated with inferior outcome. Recently, concurrent BCL2 (Dako clone 124, ≥30% positive) and MYC (Epitomics clone Y69, ≥40% positive) protein expression by IHC was reported to be associated with inferior outcome in DLBCL treated with R-CHOP (Johnson et al. Blood 2010, 116: Abstract 2005). We investigated the prognostic significance of BCL2 and MYC IHC in primary testicular DLBCL.
Design: A tissue microarray was constructed using duplicate 1.0mm cores from diagnostic paraffin blocks of 85 patients with primary testicular DLBCL. For survival analysis, patients not treated with curative intent or were HIV-positive were excluded, leaving 66 patients; 35 treated with R-CHOP and 31 with CHOP-like chemotherapy. FISH was performed using commercial probes for BCL2 and MYC. BCL2 (Dako clone 124 and Epitomics clone E17) and MYC IHC were performed and scored by at least 2 independent scorers. Cases were called BCL2-positive if ≥30% of cells showed BCL2 expression, and MYC-positive if ≥40% of cells showed MYC expression, as described. Survival analysis was determined by Kaplan-Meier method with differences evaluated by log-rank test.
Results: BCL2 (Dako) was positive in 76/85 cases (89%) and BCL2 (E17) was positive in 70/85 (82%). 6 cases positive for BCL2 (Dako) were negative for BCL2 (E17). All cases with BCL2 break-apart were BCL2 (Dako)-positive (5/78). MYC was positive in 16/85 (19%). 15/16 (94%) MYC-positive cases were also BCL2 (Dako)-positive. MYC break-apart was seen in 6/76 cases (8%); 4 were MYC-positive and 2 were MYC-negative (15% and 25% staining). One case had both BCL2 and MYC break-apart, and was MYC-positive (95% staining). Another case had both BCL6 and MYC break-apart, and was MYC-negative (25% staining). 11/76 cases (14%) without MYC break-apart were MYC-positive. In the subgroup for survival analysis, all MYC-positive cases were also BCL2 (Dako)-positive (13/66). In patients treated with CHOP-like chemotherapy, MYC-positive cases had significantly inferior survival (6/31 [19%] positive, OS p=0.008 and PFS p=0.018). In patients treated with R-CHOP, no significant association with MYC-positivity and survival was seen (7/35 [20%] positive). No significant association with BCL2-positivity and survival was seen.
Conclusions: MYC protein expression can occur in the absence of a MYC gene rearrangement in primary testicular DLBCL. It is significantly associated with inferior survival in primary testicular DLBCL treated with CHOP-like but not R-CHOP therapy.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 188, Tuesday Afternoon