C-MYC

The proto-oncogene c-MYC is located on chromosome 8q24. It encodes a nuclear posphoprotein that acts as a growth promotor and transcription factor regulating a variety of cellular functions such as cell growth, differentiation and apoptosis. c-MYC is involved in the regulation of 10-15% of all human genes and is estimated to be involved in 20% of all human cancers. c-MYC is essential for early B-cell development in the bone marrow and the unregulated expression of c-MYC in germinal center B-cells increases the chances of oncogentic events for the development of B-cell lymphomas.

Mutations, amplification, rearrangement, and translocation of the c-MyC gene have been associated with various hematopoietic tumors, leukemias, and lymphomas as well as a variety of carcinomas (e.g. thyroid, breast, endometrium) and gliomas.

IHC for c-MYC overexpression (>40%) is used to screen and predict c-MYC rearrangements and distinguish diffuse large B-cell lymphoma (DLBCL) NOS from high grade B-cell lymphoma with c-MYC, BCL2 and/or BCL6 rearrangements or so-called “double or triple hit lymphomas” who tend to have aggressive behavior and poor outcome when treated with standard therapy. c-MYC protein is overexpressed in 90% of Burkitt lymphomas (BL) and caused by c-Myc gene translocation.

At present and according to preliminary data supported from NordiQC reference laboratories and the NordiQC assessment Run 56, 2019, tonsil and colon are recommended as positive and negative tissue controls for c-MYC. In the tonsil, protocols must be calibrated to provide a moderate to strong, distinct nuclear staining reaction in approximately 10% of lymphocytes scattered both in the interfollicular zones and in the reactive germinal centers of the tonsil. A weak, distinct nuclear staining reaction of mantle zone B-cells (app. 10-20%) should be seen. In colon, a weak to moderate nuclear staining reaction should be displayed in scattered epithelial cells in the basal crypts, whereas the luminal epithelial cells and smooth muscle cells of the tunica muscularis should be unstained. As a supplement to the technical calibration of the IHC protocol in tonsil and colon, it is recommended to validate the protocol on BLs and DLBCLs with and without c-MYC rearrangement to monitor the analytical accuracy.