Aberrant T-cell antigen expression in classical Hodgkin lymphoma is associated with decreased event-free survival and overall survival

• Published in: Blood 2013-03, Vol.121 (10), p.1795-1804
• Main Authors: Venkataraman, Girish, Song, Joo Y., Tzankov, Alexandar, Dirnhofer, Stephan, Heinze, Georg, Kohl, Maria, Traverse-Glehen, Alexandra, Eberle, Franziska C., Hanson, Jeffrey C., Raffeld, Mark A., Pittaluga, Stefania, Jaffe, Elaine S.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Case-Control Studies; Child; Cohort Studies; DNA, Neoplasm - genetics; Female; Follow-Up Studies; Gene Rearrangement; Genes, Immunoglobulin Heavy Chain - genetics; Hodgkin Disease - genetics; Hodgkin Disease - metabolism; Hodgkin Disease - mortality; Humans; Immunoenzyme Techniques; In Situ Hybridization; Laser Capture Microdissection; Lymphoid Neoplasia; Male; Middle Aged; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - mortality; Neoplasm Staging; Polymerase Chain Reaction; Prognosis; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Reed-Sternberg Cells - metabolism; Survival Rate; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2012-06-439455

Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) rarely express T-cell-associated antigens (TCA), but the clinical significance of this finding is uncertain. Fifty cHLs expressing any TCA on the HRS cells (TCA-cHL) were identified in two cohorts (National Cancer Institute, n = 38; Basel, n = 12). Diagnostic pathology data were examined in all cases with additional T-cell receptor γ rearrangements (TRG@) polymerase chain reaction (PCR) in a subset of cases. The outcome data were compared with a cohort of cHLs negative for TCA (n = 272). Primary end points examined were event-free survival (EFS) and overall survival (OS). The median age in the TCA-cHL group was 40 years (range, 10-85 years). Seventy percent presented in low stage (stage I/II) at presentation with nodular sclerosis (NS) histology predominating in 80% of cases. Among the TCA, CD4 and CD2 were most commonly expressed, seen in 80.4% and 77.4% of cases, respectively. TRG@ PCR was negative for clonal rearrangements in 29 of 31 cases. During a median follow up of 113 months, TCA expression predicted shorter OS (adjusted hazard ratio [HRadj] = 3.32 [95% confidence interval (CI): 1.61, 6.84]; P = .001) and EFS (HRadj = 2.55 [95% CI: 1.45, 4.49]; P = .001). TCA-cHL often display NS histology, lack T-cell genotype, and are independently associated with significantly shorter OS and EFS compared with TCA-negative cHLs. •Cases of cHL may express TCA on the neoplastic cells.•TCA-cHL have nodular sclerosis histology and lack T-cell genotype, with worse outcome compared with TCA-negative cHLs.