Round-robin testing for LMO2 and MYC as immunohistochemical markers to screen MYC rearrangements in aggressive large B-cell lymphoma

Virchows Arch. 2024 Aug;485(2):307-314. doi: 10.1007/s00428-023-03584-9. Epub 2023 Jun 27.

Abstract

Aggressive large B-cell lymphomas (aLBCL) include a heterogeneous group of lymphomas with diverse biological features. One of the approaches to the diagnosis of aLBCL is based on the identification of MYC rearrangements (MYC-R), in addition to BCL2 and BCL6 rearrangements by genetic techniques, mainly fluorescent in situ hybridization (FISH). Because of the low incidence of MYC-R, the identification of useful immunohistochemistry markers to select cases for MYC FISH testing may be useful in daily practice. In a previous work, we identified a strong association between the profile CD10 positive/LMO2 negative expression and the presence of MYC-R in aLBCL and obtained good intralaboratory reproducibility. In this study, we wanted to evaluate external reproducibility. To evaluate whether LMO2 can be a reproducible marker between observers 50 aLBCL cases were circulated among 7 hematopathologists of 5 hospitals. Fleiss' kappa index for LMO2 and MYC were 0.87 and 0.70, respectively, indicating high agreement between observers. In addition, during 2021-2022, the enrolled centers included LMO2 in their diagnostic panels to evaluate prospectively the utility of the marker, and 213 cases were analyzed. Comparing LMO2 with MYC, the group of CD10 positive cases showed higher specificity (86% vs 79%), positive predictive value (66% vs 58%), likelihood positive value (5.47 vs 3.78), and accuracy (83% vs 79%), whereas the negative predictive values remained similar (90% vs 91%). These findings place LMO2 as a useful and reproducible marker to screen MYC-R in aLBCL.

Keywords: Large B-cell lymphoma; Lymphomas; MYC, LMO2, FISH.

Publication types

  • Multicenter Study

MeSH terms

  • Adaptor Proteins, Signal Transducing* / analysis
  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Female
  • Gene Rearrangement*
  • Humans
  • Immunohistochemistry*
  • In Situ Hybridization, Fluorescence
  • LIM Domain Proteins* / genetics
  • LIM Domain Proteins* / metabolism
  • Lymphoma, Large B-Cell, Diffuse* / diagnosis
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Proto-Oncogene Proteins c-myc* / genetics
  • Proto-Oncogene Proteins* / genetics
  • Reproducibility of Results

Substances

  • LMO2 protein, human
  • LIM Domain Proteins
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-myc
  • Adaptor Proteins, Signal Transducing
  • MYC protein, human
  • Proto-Oncogene Proteins