High-throughput tissue microarray analysis of GI -cyclin alterations in classical Hodgkin's lymphoma indicates overexpression of cyclin EI

Alexander Tzankov, Annette Zimpfer, Alessandro Lugli, Jens Krugmann, Philip Went, Peter Schraml, Robert Maurer, Stefano Ascani, Stefano Pileri, Stephan Geley, Stephan Dimhofer

Research output: Contribution to journalArticle

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Abstract

Deregulation of G1-cyclins (CCN) plays a key role in the pathogenesis of many human malignancies, including non-Hodgkin's lymphomas (NHLs). In contrast to NHL, little is known about phenotypic and genotypic changes in the regulation of the cell cycle in classical Hodgkin's lymphoma (cHL). To facilitate analysis of aberrant gene expression in cHL, a lymphoma tissue microarray (TMA) containing 752 cores of 330 different cHL samples was constructed. Direct comparison of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) expression in Hodgkin's and Reed-Sternberg (HRS) cells on conventional full sections with the corresponding duplicate/triplicate tumour cores on the TMA showed a concordance of 100%, indicating that cHL-TMA is a reliable and representative method for evaluating gene expression profiles in situ. Using TMA technology, protein expression and gene amplification of different G1-CCNs in cHL were analysed. Among the G1-CCNs analysed, cyclin E (CCNE) was expressed in 212/253 cases (84%). In most of the individual tumours, over 75% of the HRS cells stained positive for CCNE, suggesting that CCNE is overexpressed in cHL. This overexpression was not due to CCNE gene amplification, as judged by fluorescence in situ hybridization, and did not correlate with EBV infection, as assessed by the expression of LMP-1. Thus, the overexpression of CCNE could be caused by profound changes in HRS cell-cycle regulation that could contribute to the malignant phenotype.

Original languageEnglish
Pages (from-to)201-207
Number of pages7
JournalJournal of Pathology
Volume199
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

Fingerprint

Tissue Array Analysis
Cyclins
Hodgkin Disease
Cyclin E
Reed-Sternberg Cells
Gene Amplification
Non-Hodgkin's Lymphoma
Cell Cycle
Cyclin G1
Neoplasms
Protein Array Analysis
Epstein-Barr Virus Infections
Fluorescence In Situ Hybridization
Transcriptome
Lymphoma
Membrane Proteins
Technology
Phenotype
Gene Expression

Keywords

  • Cyclin E
  • Epstein-Barr virus
  • G1-cyclins
  • Hodgkin's lymphoma
  • Tissue microarray

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

High-throughput tissue microarray analysis of GI -cyclin alterations in classical Hodgkin's lymphoma indicates overexpression of cyclin EI. / Tzankov, Alexander; Zimpfer, Annette; Lugli, Alessandro; Krugmann, Jens; Went, Philip; Schraml, Peter; Maurer, Robert; Ascani, Stefano; Pileri, Stefano; Geley, Stephan; Dimhofer, Stephan.

In: Journal of Pathology, Vol. 199, No. 2, 01.02.2003, p. 201-207.

Research output: Contribution to journalArticle

Tzankov, A, Zimpfer, A, Lugli, A, Krugmann, J, Went, P, Schraml, P, Maurer, R, Ascani, S, Pileri, S, Geley, S & Dimhofer, S 2003, 'High-throughput tissue microarray analysis of GI -cyclin alterations in classical Hodgkin's lymphoma indicates overexpression of cyclin EI', Journal of Pathology, vol. 199, no. 2, pp. 201-207. https://doi.org/10.1002/path.1279
Tzankov, Alexander ; Zimpfer, Annette ; Lugli, Alessandro ; Krugmann, Jens ; Went, Philip ; Schraml, Peter ; Maurer, Robert ; Ascani, Stefano ; Pileri, Stefano ; Geley, Stephan ; Dimhofer, Stephan. / High-throughput tissue microarray analysis of GI -cyclin alterations in classical Hodgkin's lymphoma indicates overexpression of cyclin EI. In: Journal of Pathology. 2003 ; Vol. 199, No. 2. pp. 201-207.
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abstract = "Deregulation of G1-cyclins (CCN) plays a key role in the pathogenesis of many human malignancies, including non-Hodgkin's lymphomas (NHLs). In contrast to NHL, little is known about phenotypic and genotypic changes in the regulation of the cell cycle in classical Hodgkin's lymphoma (cHL). To facilitate analysis of aberrant gene expression in cHL, a lymphoma tissue microarray (TMA) containing 752 cores of 330 different cHL samples was constructed. Direct comparison of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) expression in Hodgkin's and Reed-Sternberg (HRS) cells on conventional full sections with the corresponding duplicate/triplicate tumour cores on the TMA showed a concordance of 100{\%}, indicating that cHL-TMA is a reliable and representative method for evaluating gene expression profiles in situ. Using TMA technology, protein expression and gene amplification of different G1-CCNs in cHL were analysed. Among the G1-CCNs analysed, cyclin E (CCNE) was expressed in 212/253 cases (84{\%}). In most of the individual tumours, over 75{\%} of the HRS cells stained positive for CCNE, suggesting that CCNE is overexpressed in cHL. This overexpression was not due to CCNE gene amplification, as judged by fluorescence in situ hybridization, and did not correlate with EBV infection, as assessed by the expression of LMP-1. Thus, the overexpression of CCNE could be caused by profound changes in HRS cell-cycle regulation that could contribute to the malignant phenotype.",
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AU - Krugmann, Jens

AU - Went, Philip

AU - Schraml, Peter

AU - Maurer, Robert

AU - Ascani, Stefano

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AU - Geley, Stephan

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