New MYC IHC Classifier Integrating Quantitative Architecture Parameters to Predict MYC Gene Translocation in Diffuse Large B-Cell Lymphoma.
A new automated MYC IHC classifier based on bivariate logistic regression is presented. The predictor relies on image analysis developed with the open-source ImageJ platform. From a histologic section immunostained for MYC protein, 2 dimensionless quantitative variables are extracted: (a) relative distance between nuclei positive for MYC IHC based on euclidean minimum spanning tree graph and (b) coefficient of variation of the MYC IHC stain intensity among MYC IHC-positive nuclei. Distance between positive nuclei is suggested to inversely correlate MYC gene rearrangement status, whereas coefficient of variation is suggested to inversely correlate physiological regulation of MYC protein expression. The bivariate classifier was compared with 2 other MYC IHC classifiers (based on percentage of MYC IHC positive nuclei), all tested on 113 lymphomas including mostly diffuse large B-cell lymphomas with known MYC fluorescent in situ hybridization (FISH) status. The bivariate classifier strongly outperformed the "percentage of MYC IHC-positive nuclei" methods to predict MYC+ FISH status with 100% sensitivity (95% confidence interval, 94-100) associated with 80% specificity. The test is rapidly performed and might at a minimum provide primary IHC screening for MYC gene rearrangement status in diffuse large B-cell lymphomas. Furthermore, as this bivariate classifier actually predicts "permanent overexpressed MYC protein status," it might identify nontranslocation-related chromosomal anomalies missed by FISH.
Departments of Laboratory Medicine and Pathology, Cross Cancer Institute.
Gilbert
G
Bigras
Departments of Laboratory Medicine and Pathology, Cross Cancer Institute.
Wei-Feng
WF
Dong
Departments of Laboratory Medicine and Pathology, Cross Cancer Institute.
Sarah
S
Canil
Departments of Laboratory Medicine and Pathology, Cross Cancer Institute.
Raymond
R
Lai
Becton Dickinson, Office of Science, Medicine and Technology, Corporate Clinical Development, Pont-de-Claix, France.
Didier
D
Morel
Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
Paul E
PE
Swanson
Laboratory Medicine and Pathology, Molecular Pathology Division, University of Alberta, Edmonton.
Iyare
I
Izevbaye
D003936:Diagnosis, Computer-Assisted / Q000379:methods* / Q000592:standards*; D019937:Diagnostic Techniques and Procedures; D005544:Forecasting; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000235:genetics*; D014178:Translocation, Genetic