HLA class II expression by Hodgkin Reed-Sternberg cells is an independent prognostic factor in classical Hodgkin's lymphoma.
OBJECTIVE
The neoplastic Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin's lymphoma (cHL) are derived from B cells. The frequency of HLA class II downregulation and its effect on prognosis are unknown.


METHODS
Immunohistochemistry results for HLA class II were evaluated in 292 primary cHL patients in a population-based approach. Patients were diagnosed between 1989 and 2000 in the northern part of the Netherlands. Median age at diagnosis was 38 years (range, 8 to 88 years); 63% had Ann Arbor stage I or II, 24% stage III, and 13% stage IV disease. Median follow-up was 7.1 years. For 168 patients, HLA genotype data were available.


RESULTS
Lack of HLA class II cell-surface expression on HRS cells was observed in 41.4% and was more common in patients with extranodal disease, patients with Epstein-Barr virus-negative disease, and patients with HLA class I-negative HRS cells. Alleles of three microsatellite markers in the HLA class II region were associated with presence or absence of protein expression. In univariate analyses, lack of HLA class II expression coincided with adverse outcome (5-years failure free survival [FFS], 67% v 85%; P = .001; 5-years age and sex matched relative survival (RS), 80% v 90%; P = .027). This effect remained in multivariate analyses for FFS with a hazard ratio of 2.40 (95% CI, 1.45 to 3.98) and RS with a relative excess risk of death of 2.55 (95% CI, 1.22 to 5.31).


CONCLUSIONS
Lack of membranous HLA class II expression by HRS cells in diagnostic lymph node specimens is an independent adverse prognostic factor in cHL.
Diepstra
Arjan
A
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands. a.diepstra@path.umcg.nl
van Imhoff
Gustaaf W
GW
Karim-Kos
Henrike E
HE
van den Berg
Anke
A
te Meerman
Gerard J
GJ
Niens
Marijke
M
Nolte
Ilja M
IM
Bastiaannet
Esther
E
Schaapveld
Michael
M
Vellenga
Edo
E
Poppema
Sibrand
S
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002423:Cause of Death; D002648:Child; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000235:genetics; D006689:Hodgkin Disease / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D016539:Reed-Sternberg Cells / Q000276:immunology*; D012042:Registries; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012737:Sex Factors; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D000949:Histocompatibility Antigens Class II