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

• Published in: American journal of clinical pathology 2007-12, Vol.128 (6), p.958-965
• Main Authors: KELLEY, Todd W, POHLMAN, Brad, ELSON, Paul, HSI, Eric D
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cell Count; Child; Child, Preschool; Female; Forkhead Transcription Factors - metabolism; Granzymes - metabolism; Hematologic and hematopoietic diseases; Hodgkin Disease - immunology; Hodgkin Disease - mortality; Hodgkin Disease - pathology; Humans; Investigative techniques, diagnostic techniques (general aspects); Killer Cells, Natural - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes, Tumor-Infiltrating - immunology; Male; Medical sciences; Membrane Transport Proteins - metabolism; Middle Aged; Myelin and Lymphocyte-Associated Proteolipid Proteins; Myelin Proteins - metabolism; Neoplasm Staging; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Proteolipids - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Retrospective Studies; Survival Rate; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Regulatory - immunology; Tissue Array Analysis
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1309/NB3947K383DJ0LQ2

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.