Utilization of MYC Immunohistochemistry in Aggressive B-Cell Lymphomas To Predict an Underlying MYC Gene Rearrangement
Nichole Steidler, Giovanni Insuasti-Beltran, Ronald Schrader, Kaaren Reichard. University of New Mexico, Albuquerque, NM
Background: Rearrangements of the MYC oncogene drive proliferation and are associated with increased aggressiveness in some B-cell lymphomas. A MYC gene rearrangement has both prognostic and diagnostic utility in Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DBLCL) and B-cell lymphoma unclassifiable (BCLU). Recent studies report that specific patterns of MYC immunohistochemistry may predict an underlying MYC gene rearrangement. Given that turn around time for traditional methods for detection of MYC gene rearrangements (e.g. cytogenetics, fluorescence in situ hybridization) is typically longer than for immunohistochemistry, we aimed to determine if MYC immunohistochemistry could predict an underlying MYC gene rearrangement.
Design: 34 BL, 29 DLBCL without MYC rearrangement, 4 DLBCL with MYC rearrangement, 8 BCLU cases and 12 DLBCL with additional copies of the MYC gene region but no rearrangement were evaluated for percentage and intensity of tumor cells staining by MYC immunohistochemistry. 16 of 87 cases (18%) were excluded due to poor tissue fixation. MYC immunohistochemistry (Epitomics clone Y69) was performed on paraffin-embedded formalin-fixed tissues at a 1:50 titer. Fluorescence in situ hybridization (FISH) was performed in every case to confirm presence or absence of an underlying MYC rearrangement. Blinded to the pathologic diagnosis, three pathologists evaluated each case using a 3-tiered system (1+ to 3+, weak to strong) to grade intensity of MYC nuclear immunohistochemical staining and to assign percent positive cells.
Results: The average percentage of tumor cells positive by MYC immunohistochemistry was 95% for BL, 98% for BCLU, 100% for DLBCL with MYC rearrangement, 56% for DLBCL without MYC rearrangement and 50% for DLBCL with additional MYC copies (p = 0.0005). BL and BCLU tended to have intensity 3+, DLBCL with MYC rearrangement tended to have intensity 2+, and DLBCL without MYC rearrangement and DLBCL with additional MYC copies tend to have intensity 1+ (p=0.0003).
Conclusions: Detection of MYC protein expression by immunohistochemistry is a valuable tool in the evaluation of aggressive B-cell lymphomas. In this study, we found that strongly positive MYC immunohistochemistry (2+ and 3+) can predict an underlying MYC gene rearrangement. This finding could have potential cost savings by negating the need for FISH in some cases. An important caveat is the need for adequate fixation for successful evaluation of MYC immunohistochemistry.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 178, Tuesday Afternoon