title: Scoring of MYC protein expression in diffuse large B-cell lymphomas: concordance rate among hematopathologists.
abstract: Recent studies have shown that immunohistochemical evaluation of MYC protein expression in diffuse large B-cell lymphoma is a useful prognostic tool with high concordance rate among pathologists. Concordance in these studies was assessed among few pathologists from one institution by scoring tissue microarrays. In daily practice, MYC evaluation is performed on entire tumor sections by a diverse group of pathologists. In our study, nine hematopathologists from two institutions scored whole-tissue sections of two sets of cases. The training set included 13 cases of diffuse large B-cell lymphoma and 4 cases of Burkitt lymphoma. The validation set included 18 cases of diffuse large B-cell lymphoma and 1 case of Burkitt lymphoma. MYC positivity was defined as ≥40% of tumor cells demonstrating nuclear staining similar to prior studies. The mean score for each case was used to determine MYC status with discrepant cases defined as having any score causing a different MYC status designation. Discrepant cases from the training set were characterized by staining heterogeneity, extensive necrosis or crush artifact and had mean scores within 15 percentage points of 40%. Cases from the validation set that demonstrated any of these features were scored twice on two different days. Overall concordance was moderate (Kappa score: 0.68, P-value<0.001) with no significant change between the two sets (Kappa scores: 0.69 vs 0.67). Thirty-nine percent of cases were discrepant. The findings indicate that a significant number of diffuse large B-cell lymphomas are inherently difficult to score due to staining heterogeneity. The effect of heterogeneity can be under-represented when concordance is measured among few pathologists scoring tissue microarrays. Careful scoring strategy in our study failed to improve concordance. In the absence of specific instructions on how to deal with heterogeneity, caution is advised when evaluating MYC expression in diffuse large B-cell lymphoma.
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Amer Z
authors.initials: AZ
authors.lastname: Mahmoud
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Tracy I
authors.initials: TI
authors.lastname: George
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Czuchlewski
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Qian-Yun
authors.initials: QY
authors.lastname: Zhang
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Carla S
authors.initials: CS
authors.lastname: Wilson
authors.affiliation: Presbyterian Hospital, Albuquerque, NM, USA.
authors.forename: Cordelia E
authors.initials: CE
authors.lastname: Sever
authors.affiliation: Presbyterian Hospital, Albuquerque, NM, USA.
authors.forename: Alexei G
authors.initials: AG
authors.lastname: Bakhirev
authors.affiliation: Presbyterian Hospital, Albuquerque, NM, USA.
authors.forename: Dahua
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Nichole L
authors.initials: NL
authors.lastname: Steidler
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Kaaren K
authors.initials: KK
authors.lastname: Reichard
authors.affiliation: Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Huining
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Foucar
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Vasef
mesh_terms: D002051:Burkitt Lymphoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc