Prognostic Impact of Tumor Microenvironment in Diffuse Large B-Cell Lymphoma Uniformly Treated With R-CHOP Chemotherapy

Am J Clin Pathol. 2016 Apr;145(4):514-23. doi: 10.1093/ajcp/aqw034. Epub 2016 Apr 22.

Abstract

Objectives: We evaluated the prognostic impact of cell-of-origin classification as well as intratumoral regulatory T cells (Tregs), macrophages, and microvessel density (MVD) on 115 patients (74 in the training set and 41 in the validation set) diagnosed with de novo diffuse large B-cell lymphoma (DLBCL) and uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy.

Methods: The prognostic impact of Tregs, macrophages, and MVD was evaluated using FOXP3, CD68, and CD34 immunohistochemical stains, respectively. In addition, we designed a scoring system where 1 point was awarded per each adverse prognostic factor, including non-germinal center B-cell-like subtype, FOXP3 17% or more, CD68 less than 2%, and MVD less than 800 vessels/mm(2) RESULTS: Although only MVD was statistically significant on multivariate analysis, the scoring system significantly segregated patients into low- and high-risk groups. Patients having two or more adverse prognostic factors (high-risk group) demonstrated significantly worse event-free and progression-free survivals in the training set and event-free survival in the validation set.

Conclusions: The concomitant evaluation of cell of origin along with tumor microenvironment components identifies patients with DLBCL treated with R-CHOP chemotherapy portraying a worse prognosis.

Keywords: Diffuse large B-cell lymphoma; Macrophages; Microvasculature; Prognostic impact; Regulatory T lymphocytes; Tumor microenvironment.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Combined Chemotherapy Protocols
  • Area Under Curve
  • Biomarkers, Tumor / analysis
  • Cyclophosphamide
  • Disease-Free Survival
  • Doxorubicin
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Male
  • Middle Aged
  • Prednisone
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Rituximab
  • Sensitivity and Specificity
  • Tissue Array Analysis
  • Tumor Microenvironment* / immunology
  • Vincristine
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers, Tumor
  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone