title: Epstein-Barr virus association in classical Hodgkin's disease provides survival advantage to patients and correlates with higher expression of proliferation markers in Reed-Sternberg cells.
abstract: BACKGROUND
  Most Epstein-Barr virus (EBV) associated lymphoproliferative disorders have high proliferation indices. However, classical Hodgkin's disease (cHD) is heterogeneous, with respect to proliferation index of the Reed-Sternberg cell (RS cell), and EBV association. Hence, we investigated whether cHD with and without EBV-association differ with respect to the proliferation index of the RS cells. Further we investigated whether this would have a bearing on patients survival.
  
  
  METHODS
  We investigated 110 cases of cHD for: a) EBV association by immunohistochemical demonstration of EBV-latent membrane protein-1 and EBV encoded nuclear RNA 1 by mRNA in situ hybridisation; b) Proliferating cell nuclear antigen (PCNA) expression in the RS cells.
  
  
  RESULTS
  EBV association was noted in 86 of 110 cases (78%). Higher PCNA expression (P = 0.004) and younger age (P = 0.001) correlated independently with EBV association. The 10 year relapse free survival (RFS) of EBV+ and EBV- patients were 60% and 44%, respectively (P = 0.03). The 10 year overall survival (OS) of EBV+ and EBV- patients were 85% and 64%, respectively (P = 0.03). EBV association maintained its significant impact on RFS and OS within Cox proportional hazard model.
  
  
  CONCLUSIONS
  Our study suggests that EBV is likely to confer a higher PCNA expression and also contribute towards maintaining the RS cells of cHD in cell cycle. Hence, RS cells in EBV associated cHD would be more responsive to chemotherapy and radiotherapy associated DNA damage. Thus, EBV-association provides survival advantage to cHD patients treated with standard chemotherapy and radiotherapy protocols.
authors.affiliation: Department of Pathology, Tata Memorial Hospital, Mumbai, India. medimail@tmc.ernet.in
authors.forename: K N
authors.initials: KN
authors.lastname: Naresh
authors.forename: J
authors.initials: J
authors.lastname: Johnson
authors.forename: V
authors.initials: V
authors.lastname: Srinivas
authors.forename: C S
authors.initials: CS
authors.lastname: Soman
authors.forename: T
authors.initials: T
authors.lastname: Saikia
authors.forename: S H
authors.initials: SH
authors.lastname: Advani
authors.forename: R A
authors.initials: RA
authors.lastname: Badwe
authors.forename: K A
authors.initials: KA
authors.lastname: Dinshaw
authors.forename: M
authors.initials: M
authors.lastname: Muckaden
authors.forename: I
authors.initials: I
authors.lastname: Magrath
authors.forename: K
authors.initials: K
authors.lastname: Bhatia
mesh_terms: D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006689:Hodgkin Disease / Q000401:mortality / Q000473:pathology* / Q000821:virology*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D012367:RNA, Viral / Q000302:isolation & purification; D016539:Reed-Sternberg Cells / Q000473:pathology* / Q000821:virology*; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D014763:Viral Matrix Proteins / Q000032:analysis
chemical_list: D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D012367:RNA, Viral; D014763:Viral Matrix Proteins