High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma.
Determining the presence of MYC gene rearrangements is becoming an increasingly important part of the diagnostic workup in aggressive lymphoma. Cytogenetic MYC alterations aid in differentiating diffuse large B-cell lymphoma (DLBCL) from Burkitt lymphoma. In addition, MYC aberrations are associated with poor prognosis in DLBCL. Fluorescence in situ hybridization and karyotyping are standard tests for detecting MYC aberrations, but these techniques are laborious and expensive. Here, we studied MYC status of 219 DLBCLs and Burkitt lymphomas using fluorescence in situ hybridization, immunohistochemistry, and quantitative real-time polymerase chain reaction (QRT-PCR). Overall, 15% of the cases had an MYC break. QRT-PCR analysis of MYC expression showed that 72% of DLBCLs with an MYC break had aberrantly high or low levels of MYC transcript. Excluding the cases with aberrantly low MYC expression, we found a significant positive correlation between levels of MYC transcripts and MYC tumor cells; however, QRT-PCR is not readily applicable as a screening tool. Immunohistochemically, all tumors showed a nuclear staining pattern that was simple to evaluate. The percentage of MYC lymphoma cells correlated closely with MYC rearrangement status. In all, 93% of cases with an MYC break had ≥80% MYC cells, in contrast to 3% of nonrearranged cases (P<0.0001). Receiver operating characteristic curve analysis showed ≥70% MYC tumor cells to be the optimal cutoff (sensitivity=100%, specificity=93%). Area under the receiver operating characteristic curve was 0.992, indicating that immunostaining for Myc protein is an excellent screening test to predict whether an MYC rearrangement is present.
Department of Pathology, Odense University Hospital, Denmark. tina.green@ouh.regionsyddanmark.dk
Tina Marie
TM
Green
Ole
O
Nielsen
Karin
K
de Stricker
Zijun Y
ZY
Xu-Monette
Ken H
KH
Young
Michael Boe
MB
Møller
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000175:diagnosis; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis; D015321:Gene Rearrangement; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc