High-throughput tissue microarray analysis of G1-cyclin alterations in classical Hodgkin's lymphoma indicates overexpression of cyclin E1.
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.
Tzankov
Alexandar
A
Institute of Pathology, University of Innsbruck, Austria.
Zimpfer
Annette
A
Lugli
Alessandro
A
Krugmann
Jens
J
Went
Philip
P
Schraml
Peter
P
Maurer
Robert
R
Ascani
Stefano
S
Pileri
Stefano
S
Geley
Stephan
S
Dirnhofer
Stephan
S
D019927:Cyclin E / Q000032:analysis*; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000032:analysis*; D005784:Gene Amplification; D015870:Gene Expression; D004854:Herpesvirus 4, Human; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D040081:Protein Array Analysis / Q000379:methods*; D014763:Viral Matrix Proteins / Q000032:analysis
C534702:CCNG1 protein, human; D019927:Cyclin E; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins