Abstract
MYC is the proto-oncogene classically associated with Burkitt lymphoma (BL) located at chromosomal locus 8q24. Rearrangements of MYC are seen in nearly 100% of BL but have been reported in 3–16% of diffuse large B-cell lymphomas (DLBCLs). Rearrangements of MYC are tested for by flourescence in situ hybridization (FISH). In this study, we compared immunohistochemistry (IHC) using a monoclonal antibody directed against the human Myc protein to the current method, FISH. 31 cases were identified that had been tested for MYC rearrangements by FISH over 27 months with heterogeneity in the diagnoses: 5 BL; 10 DLBCL; 3 B-cell lymphoma unclassifiable between DLBCL and BL; 5 B-cell lymphoma not otherwise specified; 1 EBV-related B-cell lymphoma; 1 composite CLL/SLL-large cell lymphoma; and 6 designated as high-grade or aggressive B-cell lymphoma. Analysis by FISH was performed as part of the clinical workup, where a MYC rearrangement is defined as a split fusion signal in at least 5.7% of cells. Myc-IHC was interpreted as a qualitative positive (overexpressed) or negative (not overexpressed) result. 12 cases (39%) were positive for MYC rearrangements by FISH. Overall, 13 cases (42%) showed Myc overexpression by IHC, 11 of which harbored a MYC rearrangement by FISH. There were two false positives and one false negative. Thus, Myc-IHC predicted a MYC rearrangement by FISH with 92% sensitivity and 89% specificity. We can thus conclude that Myc-IHC should be a potentially useful screening tool for identifying lymphomas that may harbor a MYC rearrangement.
Highlights
The MYC proto-oncogene encodes a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis, and cellular transformation [1]
The purpose of this study is to evaluate the effectiveness of Myc-IHC in predicting MYC rearrangement by flourescence in situ hybridization (FISH) in mature B-cell lymphomas
One case of diffuse large B-cell lymphomas (DLBCLs) that showed a MYC rearrangement by FISH was negative by IHC, which was regarded as a false negative
Summary
The MYC proto-oncogene encodes a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis, and cellular transformation [1]. Chromosomal translocations juxtaposing MYC to immunoglobulin enhancers were documented in B-cell Burkitt lymphomas (BLs) [4]. These were located at chromosomal locus 8q24 [4]. MYC gene alterations have been identified in mature B-cell neoplasms that are usually associated with an aggressive clinical behavior [8]. In the United States, mature B-cell neoplasms account for approximately three-quarters of all lymphoid neoplasms [9]. They comprise the majority of diffuse large B-cell lymphoma (DLBCL), BL, chronic
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