MYC IHC and MYC FISH Are Complementary Diagnostic Tests in the Routine Evaluation of Diffuse Large B-Cell Lymphoma
Michael Kluk, Heather Sun, Hongbo Yu, Paola Dal Cin, Geraldine S Pinkus, Scott Rodig. Brigham and Women's Hospital, Boston, MA; UMass Memorial Medical Center, Worcester, MA
Background: Recent retrospective analyses indicate that patients with diffuse large B-cell lymphomas (DLBCLs) expressing high MYC protein or harboring a MYC rearrangement have inferior clinical outcome when treated with standard chemotherapy. However, it is unclear whether MYC immunohistochemistry (IHC) can serve as a surrogate for MYC fluorescent in situ hybridization (FISH) in daily practice.
Design: We instituted parallel, prospective MYC IHC and MYC FISH testing at the time of diagnosis for 139 consecutive cases of DLBCL at two institutions over a 9 month period. MYC IHC was performed at both institutions using the same automated platform (Ventana Medical Systems). MYC FISH was performed at each institution using a break-apart probe according to standard protocols.
Results: MYC IHC showed high reproducibility between institutions and over time using control tissues. For DLBCL cases, a MYC IHC score was successfully reported for 137 cases (98%), and FISH was successfully reported for 129 cases (93%). Overall, 79 cases (57%) were classified as MYC IHC-high (>50% tumor nuclei positive). There were 22 cases (16%) with a MYC rearrangement detected by FISH. MYC IHC successfully detected all DLBCL cases with a MYC rearrangement except for three cases (19/22, 86%). Re-examination of DLBCLs scored as MYC IHC-low, but harboring a MYC rearrangement, revealed one case with a borderline positive FISH result (4% nuclei positive for rearrangement, (FISH cutoff = 3%)), one case with limited residual neoplastic tissue for IHC evaluation, and one case with relatively discrete foci of MYC IHC-high positivity (>50%), suggesting heterogeneous subpopulations. Approximately one-half of cases (11/21) with extra copies (but not rearrangements) of MYC were MYC IHC-high.
Conclusions: Using standardized methods in daily practice, MYC IHC is reproducible and can identify the vast majority of cases with an underlying MYC rearrangement; however, limiting quantity and/or quality of tissue available for IHC can affect results. MYC IHC and FISH show a comparable susceptibility to technical failure and therefore, application of both IHC and FISH is recommended. MYC IHC provides an additional benefit by identifying MYC protein-high cases which lack a MYC rearrangement and by characterizing protein expression in cases with extra copies of the MYC locus.
Monday, March 4, 2013 1:00 PM
Poster Session II # 201, Monday Afternoon