HLA class II expression by Hodgkin Reed-Sternberg cells is an independent prognostic factor in classical Hodgkin's lymphoma

Arjan Diepstra; Gustaaf W. van Imhoff; Henrike E. Karim-Kos; Anke van den Berg; Gerard J. te Meerman; Marijke Niens; Ilja M. Nolte; Esther Bastiaannet; Michael Schaapveld; Edo Vellenga; Sibrand Poppema

doi:10.1200/JCO.2006.10.0917

HLA class II expression by Hodgkin Reed-Sternberg cells is an independent prognostic factor in classical Hodgkin's lymphoma

Arjan Diepstra^*, Gustaaf W. van Imhoff, Henrike E. Karim-Kos, Anke van den Berg, Gerard J. te Meerman, Marijke Niens, Ilja M. Nolte, Esther Bastiaannet, Michael Schaapveld, Edo Vellenga, Sibrand Poppema

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Purpose

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. Patients and

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).

Conclusion

Lack of membranous HLA class II expression by HRS cells in diagnostic lymph node specimens is an independent adverse prognostic factor in cHL.

Original language	English
Pages (from-to)	3101-3108
Number of pages	8
Journal	Journal of Clinical Oncology
Volume	25
Issue number	21
DOIs	https://doi.org/10.1200/JCO.2006.10.0917
Publication status	Published - 20-Jul-2007
Event	47th Annual Meeting of the American-Society-of-Hematology - , Gabon Duration: 10-Dec-2005 → 13-Dec-2005

Keywords

REGULATORY T-CELLS
POSITRON-EMISSION-TOMOGRAPHY
POOR PATIENT SURVIVAL
COMPLEX CLASS-I
PROTEIN EXPRESSION
TISSUE MICROARRAY
CHEMOKINE TARC
SERUM-LEVELS
DISEASE
LYMPHOCYTES

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HLA Class II Expression by Hodgkin Reed-Sternberg Cells
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Diepstra, A., van Imhoff, G. W., Karim-Kos, H. E., van den Berg, A., te Meerman, G. J., Niens, M., Nolte, I. M., Bastiaannet, E., Schaapveld, M., Vellenga, E., & Poppema, S. (2007). HLA class II expression by Hodgkin Reed-Sternberg cells is an independent prognostic factor in classical Hodgkin's lymphoma. Journal of Clinical Oncology, 25(21), 3101-3108. https://doi.org/10.1200/JCO.2006.10.0917

@article{5db574fde7b145fcad403d386c508483,

title = "HLA class II expression by Hodgkin Reed-Sternberg cells is an independent prognostic factor in classical Hodgkin's lymphoma",

abstract = "PurposeThe 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. Patients andMethodsImmunohistochemistry 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.ResultsLack 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).ConclusionLack of membranous HLA class II expression by HRS cells in diagnostic lymph node specimens is an independent adverse prognostic factor in cHL.",

keywords = "REGULATORY T-CELLS, POSITRON-EMISSION-TOMOGRAPHY, POOR PATIENT SURVIVAL, COMPLEX CLASS-I, PROTEIN EXPRESSION, TISSUE MICROARRAY, CHEMOKINE TARC, SERUM-LEVELS, DISEASE, LYMPHOCYTES",

author = "Arjan Diepstra and \{van Imhoff\}, \{Gustaaf W.\} and Karim-Kos, \{Henrike E.\} and \{van den Berg\}, Anke and \{te Meerman\}, \{Gerard J.\} and Marijke Niens and Nolte, \{Ilja M.\} and Esther Bastiaannet and Michael Schaapveld and Edo Vellenga and Sibrand Poppema",

note = "Article; 47th Annual Meeting of the American-Society-of-Hematology ; Conference date: 10-12-2005 Through 13-12-2005",

year = "2007",

month = jul,

day = "20",

doi = "10.1200/JCO.2006.10.0917",

language = "English",

volume = "25",

pages = "3101--3108",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "AMER SOC CLINICAL ONCOLOGY",

number = "21",

}

Diepstra, A , van Imhoff, GW, Karim-Kos, HE, van den Berg, A, te Meerman, GJ, Niens, M, Nolte, IM, Bastiaannet, E, Schaapveld, M, Vellenga, E & Poppema, S 2007, 'HLA class II expression by Hodgkin Reed-Sternberg cells is an independent prognostic factor in classical Hodgkin's lymphoma', Journal of Clinical Oncology, vol. 25, no. 21, pp. 3101-3108. https://doi.org/10.1200/JCO.2006.10.0917

TY - JOUR

T1 - HLA class II expression by Hodgkin Reed-Sternberg cells is an independent prognostic factor in classical Hodgkin's lymphoma

AU - Diepstra, Arjan

AU - van Imhoff, Gustaaf W.

AU - Karim-Kos, Henrike E.

AU - van den Berg, Anke

AU - te Meerman, Gerard J.

AU - Niens, Marijke

AU - Nolte, Ilja M.

AU - Bastiaannet, Esther

AU - Schaapveld, Michael

AU - Vellenga, Edo

AU - Poppema, Sibrand

N1 - Article

PY - 2007/7/20

Y1 - 2007/7/20

N2 - PurposeThe 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. Patients andMethodsImmunohistochemistry 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.ResultsLack 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).ConclusionLack of membranous HLA class II expression by HRS cells in diagnostic lymph node specimens is an independent adverse prognostic factor in cHL.

AB - PurposeThe 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. Patients andMethodsImmunohistochemistry 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.ResultsLack 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).ConclusionLack of membranous HLA class II expression by HRS cells in diagnostic lymph node specimens is an independent adverse prognostic factor in cHL.

KW - REGULATORY T-CELLS

KW - POSITRON-EMISSION-TOMOGRAPHY

KW - POOR PATIENT SURVIVAL

KW - COMPLEX CLASS-I

KW - PROTEIN EXPRESSION

KW - TISSUE MICROARRAY

KW - CHEMOKINE TARC

KW - SERUM-LEVELS

KW - DISEASE

KW - LYMPHOCYTES

U2 - 10.1200/JCO.2006.10.0917

DO - 10.1200/JCO.2006.10.0917

M3 - Article

C2 - 17536082

SN - 0732-183X

VL - 25

SP - 3101

EP - 3108

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 21

T2 - 47th Annual Meeting of the American-Society-of-Hematology

Y2 - 10 December 2005 through 13 December 2005

ER -

HLA class II expression by Hodgkin Reed-Sternberg cells is an independent prognostic factor in classical Hodgkin's lymphoma

Abstract

Keywords

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