Fluorescent nanoparticle-mediated semiquantitative MYC protein expression analysis in morphologically diffuse large B-cell lymphoma

Pathol Int. 2021 Sep;71(9):594-603. doi: 10.1111/pin.13131. Epub 2021 Jun 25.

Abstract

The current World Health Organization (WHO) classification defines a new disease entity of high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, making fluorescence in situ hybridization (FISH) screening for these genes mandatory. In addition, the prognostic significance of MYC expression was reported, with a cut-off value of 40%. However, interobserver discrepancies arise due to the heterogeneous intensity of MYC expression by immunohistochemistry. Moreover, a cut-off value of positivity for MYC protein in diffuse large B-cell lymphoma (DLBCL) varies among studies at present. Here, we applied a high-sensitivity semiquantitative immunohistochemical technique using fluorescent nanoparticles called phosphor-integrated dots (PID) to evaluate the MYC expression in 50 de novo DLBCL cases, and compared it with the conventional diaminobenzidine (DAB)-developing system. The high MYC expression detected by the PID-mediated system predicted poor overall survival in DLBCL patients. However, we found no prognostic value of MYC protein expression for any cut-off value by the DAB-developing system, even if the intensity was considered. These results indicate that the precise evaluation of MYC protein expression can clarify the prognostic values in DLBCL, irrespective of MYC rearrangement.

Keywords: MYC; PID; diffuse large B-cell lymphoma; fluorescent nanoparticles; high grade B-cell lymphoma; immunohistochemistry; phosphor-integrated dots.

MeSH terms

  • 3,3'-Diaminobenzidine / chemistry
  • Adult
  • Aged
  • Female
  • Gene Rearrangement
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Luminescent Agents / chemistry
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Male
  • Middle Aged
  • Nanoparticles / chemistry*
  • Prognosis
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Young Adult

Substances

  • Luminescent Agents
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • 3,3'-Diaminobenzidine