title: The ratio of FOXP3+ regulatory T cells to granzyme B+ cytotoxic T/NK cells predicts prognosis in classical Hodgkin lymphoma and is independent of bcl-2 and MAL expression.
abstract: We studied the prognostic importance of tumor-infiltrating regulatory T lymphocytes (Tregs) and cytotoxic T/NK lymphocytes (CTLs) in 98 diagnostic biopsy specimens from patients with classical Hodgkin lymphoma (cHL). Immunohistochemical analysis was performed for FOXP3 to identify Tregs and for granzyme B (GrB) to identify activated CTLs. Failure-free survival (FFS) and overall survival (OS) were clinical end points. Patients with fewer than 25 FOXP3+ cells per high-power field (HPF) had a mean +/- SD 5-year FFS of 64% +/- 7% vs 85% +/- 5% for patients with 25 or more FOXP3+ cells/HPF (P = .05). A FOXP3/GrB ratio of 1 or less was associated with poor FFS (46% +/- 10% vs 86% +/- 4%; P < .001) and OS (67% +/- 10% vs 93% +/- 3%; P < .001). When prior available MAL and bcl-2 expression data were included in a multivariate analysis of all clinical and biologic factors, a FOXP3/GrB ratio of 1 or less and tumor cell expression of MAL and bcl-2 all independently predicted poor FFS. This demonstrates the importance of evaluating tumor cell markers and the tumor immune infiltrate when considering biologic prognostic markers in cHL.
authors.affiliation: Department of Clinical Pathology, Cleveland Clinic Taussig Cancer Center, Cleveland, OH 44195, USA.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Kelley
authors.forename: Brad
authors.initials: B
authors.lastname: Pohlman
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D053804:Granzymes / Q000378:metabolism*; D006689:Hodgkin Disease / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged; D009185:Myelin Proteins / Q000378:metabolism*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009367:Neoplasm Staging; D011510:Proteolipids / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C569026:MAL protein, human; D026901:Membrane Transport Proteins; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D011510:Proteolipids; D019253:Proto-Oncogene Proteins c-bcl-2; D053804:Granzymes