Altered Subcellular Localization of the c-Myc Protein Distinguishes Burkitt Lymphoma from Aggressive B-Cell Lymphomas without a c-MYC Translocation
MB Ruzinova, T Caron, SJ Rodig. Brigham and Women's Hospital, Boston, MA
Background: Burkitt lymphoma (BL) is a tumor of mature B cells with a high proliferation rate and a balanced translocation involving c-MYC. In general, BL is characterized by a set of recognizable morphologic and immunophenotypic features that prompts pathologists to pursue confirmatory genetic testing. However, cases with atypical features are often encountered and, to date, no morphologic or immunophenotypic finding can predict the presence of a c-MYC abnormality with certainty.
Design: We used a novel monoclonal antibody that recognizes c-myc to analyze 39 genetically defined, formalin-fixed, paraffin embedded tumors by standard immunohistochemistry. Cases consisted of 14 BL with confirmed c-MYC translocation, 21 diffuse large B cell lymphomas without c-MYC translocation (DLBCL; MYC-), and 4 diffuse large B cell lymphomas with c-MYC translocation (DLBCL; MYC+). The intensity and subcellular localization of positively stained tumor cells were determined independently by 2 pathologists in a blinded fashion.
Results: C-myc protein expression was detected in the tumor cells of all cases regardless of c-MYC status. In BL, c-myc protein primarily localized to the nucleus of the tumor cells (12/14 cases, 86%). In contrast, in DLBCL; MYC-, c-myc protein primarily localized to the cytoplasm and often, in a perinuclear distribution suggesting enrichment within the golgi apparatus (20/21 cases, 95%). For the diagnosis of BL, the positive predictive value of nuclear c-myc localization was 92%, and the negative predictive value of cytoplasmic c-myc localization was 91%. In DLBCL; MYC+ we observed a mixture of c-myc staining patterns reflecting the heterogeneity of the tumors.
|Diagnosis||Total Cases||Nuclear staining (%)||Cytoplasmic staining (%)||Mix Nuclear; Cytoplasmic (%)|
|BL||14||12 (86)||1 (7)||1 (7)|
|DLBCL; MYC-||21||0 (0)||20 (95)||1 (5)|
|DLBCL; MYC+||4||1 (25)||1 (25)||2 (50)|