Immunohistochemical pattern of c-MYC protein judged as "+/(weak)+/-" by a new notation correlates with MYC gene nontranslocation in large B-cell lymphoma

Hum Pathol. 2019 Mar:85:112-118. doi: 10.1016/j.humpath.2018.10.025. Epub 2018 Nov 15.

Abstract

Immunohistochemistry is not only the most important tool for pathologists to establish a final diagnosis, but it can also inform decisions regarding optimal treatment methods. However, there is no universal standard notation for expressing immunohistochemical findings. For a diagnosis of malignant lymphoma, it is important to confirm the presence or absence of MYC translocation and communicate these results to a clinical audience. However, the criteria for selecting cases for fluorescence in situ hybridization (FISH) analysis to confirm MYC translocation are ill defined. We therefore devised a notation that we termed proportion of immunoreactivity/expression for immunohistochemistry (PRIME notation) based on the cellular proportion showing different antigen-antibody reactivity in immunohistochemistry (CPAR) and used it to examine the relationship between MYC translocation and the proportion of c-MYC+ lymphoma cells. We reviewed 82 cases diagnosed as diffuse large B-cell lymphoma or diffuse large B-cell lymphoma coexisting with grade 3A to 3B follicular lymphoma. The most common notation was "+/(weak)+/-" (49/82 cases [59.8%]); cases that were CPAR positive, weakly positive, and negative for tumor cells each accounted for about one-third of the total. Unexpectedly, no MYC translocation was observed by FISH in this group. Thus, FISH is not needed even if more than half of cells are c-MYC positive by PRIME notation. This is the first report describing a correspondence between immunohistochemical findings and chromosomal abnormality, reflecting findings at the protein and gene levels, respectively.

Keywords: CPAR; FISH; Immunohistochemistry; MYC; PRIME notation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Gene Rearrangement*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymphoma, Follicular / genetics
  • Lymphoma, Follicular / metabolism*
  • Lymphoma, Follicular / pathology
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*

Substances

  • Biomarkers, Tumor
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc