title: Prognostic Impact of Tumor Microenvironment in Diffuse Large B-Cell Lymphoma Uniformly Treated With R-CHOP Chemotherapy.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Department of Pathology, Henry Ford Hospital, Detroit, MI Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Gomez-Gelvez
authors.affiliation: Department of Pathology, University of Utah and ARUP Institute for Experimental Pathology, Salt Lake City, UT.
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Salama
authors.affiliation: Department of Pathology, University of Utah and ARUP Institute for Experimental Pathology, Salt Lake City, UT.
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Perkins
authors.affiliation: Department of Pathology, Intermountain Health System, Salt Lake City, UT.
authors.forename: Matthew
authors.initials: M
authors.lastname: Leavitt
authors.affiliation: From the Department of Pathology, Henry Ford Hospital, Detroit, MI kinamda1@hfhs.org.
authors.forename: Kedar V
authors.initials: KV
authors.lastname: Inamdar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis; D003520:Cyclophosphamide; D018572:Disease-Free Survival; D004317:Doxorubicin; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011241:Prednisone; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D000069283:Rituximab; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment / Q000276:immunology; D014750:Vincristine; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Diffuse large B-cell lymphoma; Macrophages; Microvasculature; Prognostic impact; Regulatory T lymphocytes; Tumor microenvironment