MYC Immunohistochemistry Correlates with MYC Gene Rearrangement Status in Pediatric Burkitt Lymphoma and Diffuse Large B-Cell Lymphoma
Brian Y Merritt, Dolores H Lopez-Terrada, Stephen J Simko, Andrea M Sheehan, Vivian S Hernandez, Angela M Major, Choladda V Curry. Baylor College of Medicine & Texas Children's Hospital, Houston, TX
Background: The majority of aggressive mature B-cell lymphomas (AMBCLs) in children are either Burkitt lymphomas (BLs) or diffuse large B-cell lymphomas (DLBCLs). Nearly all BLs carry a MYC rearrangement, compared to ∼10% of adult DLBCLs and up to 30% of pediatric DLBCLs. Recent studies report that detection of MYC protein expression by immunohistochemistry (IHC) may predict MYC rearrangement status, but these have primarily focused on adult AMBCLs. We aimed to determine if detection of MYC protein expression may be useful to predict MYC rearrangement status in pediatric AMBCLs.
Design: Our pathology database was searched for BLs and DLBCLs (including post-transplant cases) from 1998-2012. Tissue microarrays (three 1-mm cores per case) were constructed from cases with sufficient material. MYC IHC (clone Y69, Epitomics) and fluorescence in situ hybridization (FISH) with Vysis LSI MYC dual color break apart rearrangement probe (Abbott Molecular) were performed. IHC was reviewed by two pathologists and graded on intensity (0 to 3+, none to strong) and percentage of nuclear staining. Cases with intensity of 1+ or above and >30% nuclear staining were considered positive by IHC (MYC-IHC+). FISH was graded from 1 to 4 if 0-25%, 26-50%, 51-75%, or >75% of tumor cells showed a MYC split signal pattern, respectively, and cases were considered positive by FISH (MYC-FISH+) with a score of 1 or above and/or if previous cytogenetic or FISH analysis demonstrated a MYC rearrangement.
Results: 97% of BLs (34/35) were MYC-IHC+, and 91% (32/35) were MYC-FISH+. MYC-IHC correlated with MYC-FISH in 100% (n=33) of BLs that had corresponding interpretable results; 32 cases were both MYC-IHC+ and MYC-FISH+, and one case was both negative by IHC (MYC-IHC-) and FISH (MYC-FISH-). 12% of DLBCLs (4/33) were MYC-IHC+, and 9% (3/33) were MYC-FISH+. MYC-IHC correlated with MYC-FISH in 97% (31/32) of DLBCLs that had corresponding interpretable results. One DLBCL that did not show correlation was MYC-IHC+ but MYC-FISH-. Of note, no significant cytoplasmic staining of tumor cells was observed in any case.
Conclusions: MYC IHC is a valuable tool for detecting increased MYC protein expression and shows high correlation with MYC gene rearrangement status, detected by karyotyping or FISH, in pediatric AMBCLs. However, correlation is not 100%, so cases with a suspected MYC translocation that are positive by IHC should be sent for confirmatory genetic testing.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 223, Monday Morning