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Multiplexed Fluorescent Immunohistochemical Staining, Imaging, and Analysis in Histological Samples of Lymphoma
Published on: January 9, 2019
MYC Immunohistochemistry to Identify MYC-Driven B-Cell Lymphomas in Clinical Practice
Michael J Kluk1, Caleb Ho1, Hongbo Yu2
1From the Department of Pathology, Brigham and Women's Hospital, Boston, MA.
Insights
MYC immunohistochemistry (IHC) effectively classifies aggressive B-cell lymphomas, but does not identify all MYC rearrangements. Combining MYC IHC with fluorescence in situ hybridization ensures comprehensive detection of MYC-driven lymphomas.
Area of Science:
- Hematology
- Oncology
- Pathology
Background:
- Immunohistochemistry with anti-MYC antibody (MYC IHC) is utilized for aggressive B-cell lymphomas.
- MYC IHC aids in tumor subclassification, prediction of MYC rearrangements, and patient outcome stratification.
Purpose of the Study:
- To evaluate the performance of MYC IHC in clinical practice for aggressive B-cell lymphomas.
Main Methods:
- MYC IHC was performed on control specimens and 256 aggressive B-cell lymphomas.
- Clinically reported IHC scores were compared with expert reviews.
Main Results:
- Control tissues demonstrated minimal daily staining variation (<5%).
- Reported and expert IHC scores showed strong correlation (r=0.86).
- MYC IHC accurately categorized tumors as "Low" or "High" when scores were ≤30% or ≥70%, respectively, but showed lower accuracy for scores between 40%-60%.
Conclusions:
- Clinically reported MYC IHC scores generally align with expert scores under optimal conditions.
- MYC IHC alone may not detect all B-cell lymphomas with MYC rearrangements.
- Combined use of MYC IHC and MYC fluorescence in situ hybridization is recommended for comprehensive identification of MYC-driven lymphomas.
Objectives:
Immunohistochemistry with anti-MYC antibody (MYC IHC) detects MYC protein in fixed samples of aggressive B-cell lymphomas and, according to the number of positive staining tumor nuclei, facilitates tumor subclassification, predicts underlying MYC rearrangements, and stratifies patient outcome. We aimed to determine the performance of MYC IHC in clinical practice.
Methods:
We reviewed MYC IHC performed on control specimens and 256 aggressive B-cell lymphomas and compared clinically reported IHC scores with experts' review.
Results:
Control tissues showed less than 5% variation in daily IHC staining. Reported and expert IHC scores were well correlated (r = 0.86) with an SD of 14.2%. Reported IHC scores 30% or less and 70% or more were accurate (94.5%) compared with experts in categorizing tumors as "MYC IHC-Low" and "MYC IHC-High," respectively, but scores 40% to 60% were not (60.3%). The mean IHC score among lymphomas with MYC rearrangements was 80%, but with a large range of scores (20%-100%). There was no statistically significant association between IHC score and MYC copy number.
Conclusions:
Under optimal conditions, clinically reported MYC IHC scores are concordant with expert scores within 15%. MYC IHC does not capture all B-cell lymphomas with MYC rearrangements, however. MYC IHC and MYC fluorescence in situ hybridization are both recommended to identify MYC-driven B-cell lymphomas.
