uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Predictors of histology, tissue eosinophilia and mast cell infiltration in Hodgkin's Lymphoma: a population-based study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Department of Epidemiology Research, Statens Serum Institut, Denmark.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Show others and affiliations
2011 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 87, no 3, 208-216 p.Article in journal (Refereed) Published
Abstract [en]

Objective:  Classical Hodgkin’s lymphoma (HL) lesions comprise few tumour cells, surrounded by numerous inflammatory cells. Like in other malignancies, the microenvironment is presumed to be clinically important in HL; however, microenvironment predictors remain poorly characterised. The aim of this study was to investigate how selected patient characteristics and genetic factors affect HL phenotype, in particular tissue eosinophilia, mast cell counts and HL histological subtype.

Methods:  In a population-based study, patients with HL were interviewed about potential HL risk factors. Available tumours, n = 448, were classified histologically; the number of eosinophils and mast cells were estimated, and eosinophil cationic protein (ECP) and eosinophil protein-x (EPX) gene polymorphisms were determined. Associations were assessed in regression models.

Results:  Self-reported history of asthma was predictive of having tumour eosinophilia [≥200 eosinophils/10 high power fields, univariate odds ratio (OR) = 2.22, 95% CI 1.06–4.64, P = 0.03]. High numbers of eosinophils were predominantly seen in patients carrying the genotype ECP434GG [multivariate relative levels (RLs) = 1.84, 95% CI 1.02–3.30, P = 0.04]. Lower number of eosinophils was seen in Epstein–Barr virus (EBV)-positive tumours (univariate RL = 0.52, 95% CI 0.3–0.9, P = 0.02) and in older patients (univariate RL = 0.85, 95% CI 0.73–0.99, P = 0.03). Well-known factors such as young age, female sex and EBV-negative status predicted nodular sclerosis histology.

Conclusion:  The number of eosinophils in HL tumours is influenced by patient traits such as asthma, ECP genotype and EBV status. EBV status was predictive of histology.

Place, publisher, year, edition, pages
2011. Vol. 87, no 3, 208-216 p.
Keyword [en]
Hodgkin lymphoma, microenvironment, eosinophils, mast cells, asthma, ECP, hives, histology
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-100591DOI: 10.1111/j.1600-0609.2011.01652.xISI: 000294022000002OAI: oai:DiVA.org:uu-100591DiVA: diva2:210613
Available from: 2009-04-02 Created: 2009-04-02 Last updated: 2015-07-22Bibliographically approved
In thesis
1. Hodgkin Lymphoma – an Interplay Between Tumour Cell and Microenvironment
Open this publication in new window or tab >>Hodgkin Lymphoma – an Interplay Between Tumour Cell and Microenvironment
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hodgkin lymphoma (HL) is a malignant disorder characterised by few tumour cells surrounded by a massive infiltrate of inflammatory cells, fibrosis, and microvessels. Therefore, it is a good model in which to study the interplay between tumour cells and the microenvironment.

In a population-based series, stage IIB had poor prognosis, equivalent to the most advanced stage (stage IV). The most prominent negative prognostic factor was tumour bulk in the mediastinum (often large fibrotic tumours).

The tumour cells expressed interleukin-9 (IL-9) in their cytoplasm in half of the cases. These cases had an over representation of nodular sclerosis histology (characterised by fibrotic bands) and infiltration of eosinophils and mast cells in the tumours. Despite this, IL-9 expression was not a negative prognostic factor.

A role of inflammatory cells is to contribute to angiogenesis. Yet, a correlation between high microvessel count and high mast cell number in HL tumours was not identified, in contrast to other lymphomas. However, a correlation to poor prognosis was seen for cases with high microvessel count.

Eosinophils contain eosinophil cationic protein (ECP). ECP was cytotoxic to cells from two HL cell lines of B-cell origin and one HL line of T-cell origin. At high concentrations, the cytotoxic effect was not as pronounced for the line of T-cell origin. If the in vitro cell lines are representative of HL in vivo, eosinophils may have different roles in different HL tumours.

In addition to the effect from tumour cells, host-related factors contribute to the inflammatory infiltrate in HL. A history of asthma and hives, and carrying the ECP434GG genotype were associated with elevated numbers of eosinophils, whereas, history of tobacco smoking was associated with lower numbers.

HL is a complex tumour consisting of recruited and subverted normal cells, fibrosis and angiogenesis: these constitute the microenvironment, which likely supports tumour cell growth, and differs between patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 66 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 449
National Category
Medical and Health Sciences
Research subject
urn:nbn:se:uu:diva-100593 (URN)978-91-554-7494-2 (ISBN)
Public defence
2009-05-16, Auditorium Minus Gustavianum, Akademigatan 3, Uppsala, 09:15 (English)
Available from: 2009-04-24 Created: 2009-04-02 Last updated: 2009-04-27Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Glimelius, IngridRubin, JennyAmini, Rose MarieVenge, PerMolin, DanielEnblad, Gunilla
By organisation
OncologyDepartment of Medical SciencesDepartment of Immunology, Genetics and Pathology
In the same journal
European Journal of Haematology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 367 hits
ReferencesLink to record
Permanent link

Direct link