Expression of the c-MYC Protein Does Not Predict an 8q24 Translocation.
Julia T Geyer, Nicholas Ippolito, Sharon Barouk, Attilio Orazi, Scott Ely. Weill Cornell Medical College, New York
Background: c-MYC is an oncogene encoding a transcription factor with numerous functions. It can be dysregulated by an 8q24 translocation in Burkitt lymphoma (BL) and as a secondary event in other hematopoietic cancers, such as diffuse large B cell lymphoma (DLBCL). Although this suggests utility of c-MYC protein detection by immunohistochemistry (IHC) for diagnostic purposes, a paraffin-reactive antibody has only recently become available. Published studies suggest that the subcellular pattern of expression correlates with the presence or absence of a c-MYC translocation. The purpose of our study was to assess correlations between c-MYC expression with 8q24 translocations and with proliferation as assessed by Ki67.
Design: The study included 64 patient biopsies, all assessed by karyotype and FISH: BL (18), other lymphoma with t(8;14) (n=11); t(8:14) negative DLBCL (n=7); low-grade B cell lymphoma (n=12), T-cell lymphoma (n=5), Hodgkin lymphoma (n=6) and reactive lymphadenopathy (n=5). A new method of light reactive double staining was used to assess protein expression in the neoplastic B cells, excluding bystander hematopoietic cells from the analysis; slides were stained for c-MYC/PAX5 and Ki-67/PAX5. Assessment of expression was performed manually and by automated image analysis. In parallel, traditional single IHC was performed for c-MYC, Ki67 and PAX5.
Results: C-MYC staining was exclusively nuclear and was positive in at least a subset of lymphocytes in all cases. Low-grade lymphomas and reactive lymph nodes had rare scattered positive cells, mostly corresponding to large activated lymphocytes, and including Reed-Sternberg cells. All lymphomas with a an 8q24 translocation had strong, uniform overexpression of c-MYC, which was exclusively nuclear. Also, all aggressive lymphomas without an 8q24 translocation showed a similar pattern of expression. The correlation between c-MYC and Ki67 in the lymphoma cells was not statistically significant.
Conclusions: Our findings show that the c-MYC antibody is a reliable immunohistochemical marker. Although it will likely be valuable in research, to assess the expression and function of c-MYC, it may not prove to be of diagnostic utility. We found that the subcellular location of the protein was the same in all cells. Low or absent c-MYC expression suggests the absence of an 8q24 translocation, but high expression is a non-specific finding.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 219, Wednesday Afternoon