p53 expression in large B-cell lymphomas with MYC extra copies and CD99 expression in large B-cell lymphomas in relation to MYC status

Hum Pathol. 2019 Apr:86:21-31. doi: 10.1016/j.humpath.2018.11.015. Epub 2018 Nov 26.

Abstract

p53 expression and MYC extra copies (MYC-EC) have been reported to serve as independent adverse prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL). However, the impact of p53 expression in MYC-EC lymphomas has not been delineated. Conversely, CD99 expression has been shown to have a positive impact on survival in patients with germinal center-type DLBCL, yet nothing is reported about the impact of CD99 expression and MYC status. This is the first study to evaluate p53 expression in MYC-EC lymphomas and CD99 expression in relation to MYC status. We identified 122 patients diagnosed as having large B-cell lymphoma (44, MYC-negative; 29, MYC-EC; 23, MYC rearrangement; 22, MYC and BCL2 rearrangements; 4, MYC, BCL2, and BCL6 rearrangements). p53 expression significantly correlated with DLBCL with abnormal MYC status (MYC-EC, MYC rearrangement, and MYC overexpression), but adverse p53 prognostic effect was only seen with MYC-rearranged lymphoma. CD99 expression was significantly associated with MYC-negative DLBCL and had better prognostic impact on lymphoma-specific survival (LSS), but not on relapse-free survival and overall survival. Overall, patients with MYC-EC lymphoma had significantly worse relapse-free survival and LSS than did patients with MYC-negative lymphoma, yet better overall survival and LSS than did the patients with MYC-rearranged lymphoma. Thus, patients with MYC-EC lymphomas had prognostic features that were intermediate between MYC-negative and MYC-rearranged lymphomas. Lastly, high-intensity chemotherapy (either dose-adjusted rituximab and etoposide-prednisone-vincristine-cyclophosphamide-doxorubicin or rituximab and hyperfractionated cyclophosphamide-vincristine-doxorubicin-dexamethasone treatment) did not improve survival in patients with MYC-EC and MYC-rearranged lymphoma when compared with rituximab-cyclophosphamide-hydroxydaunomycin-vincristine-prednisone therapy.

Keywords: CD99; Large B-cell lymphoma; MYC; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 12E7 Antigen / genetics
  • 12E7 Antigen / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Disease-Free Survival
  • Female
  • Gene Rearrangement
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Retrospective Studies
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • 12E7 Antigen
  • CD99 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-bcl-6
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53