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Co-expression of CD44 variant isoforms and receptor for hyaluronic acid-mediated motility (RHAMM, CD168) is an IPI- and C-MYC gene status-independent predictor of poor outcome in diffuse large B-cell lymphomas

Nagel, Sabine and Hirschmann, Petra and Dirnhofer, Stephan and Günthert, Ursula and Tzankov, Alexandar. (2010) Co-expression of CD44 variant isoforms and receptor for hyaluronic acid-mediated motility (RHAMM, CD168) is an IPI- and C-MYC gene status-independent predictor of poor outcome in diffuse large B-cell lymphomas. Experimental hematology, Vol. 38, H. 1. pp. 38-45.

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Official URL: http://edoc.unibas.ch/dok/A5251203

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Abstract

OBJECTIVE: Expression of CD44 variant (v) isoforms substantiates poor prognosis in patients with hematological malignancies. We have previously shown that CD44v6 expression in diffuse large B-cell lymphoma (DLBCL) correlates with advanced disease stage and is predominantly detected in non-germinal center (GC) B-cell like DLBCL subtypes. With the growing number of associated molecules found to form functional complexes with CD44, we analyzed a larger cohort of cyclophosphamide, doxorubicin, vincristine, prednisone- (CHOP) and equivalently treated DLBCL patients to define the prognostic role of such CD44-associated molecules. PATIENTS & METHODS: 290 formalin-fixed, paraffin-embedded primary DLBCL tissue samples were analyzed in tissue microarrays. To obtain potential biologically-meaningful associations, optimal cut-off values were established by receiver operating characteristic (ROC)-curves. The prognostic significance of every possible multimarker phenotype was also addressed. RESULTS: We showed that co-expression of any of the CD44v with the receptor for hyaluronic acid-mediated motility (RHAMM, CD168) identifies a subgroup of DLBCL patients with a very poor prognosis, independent of the international prognostic index. These patients did not show C-MYC translocations or amplifications. CD44v-RHAMM co-expression was most prevalent in non-GC DLBCL cases and usually coincided with expression of osteopontin (OPN). CONCLUSION: Evaluation of CD44v-RHAMM co-expression may improve the accuracy of DLBCL prognosis and identify a subgroup of patients, who will benefit from therapeutic alternatives to CHOP.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Neuro- und Muskelpathologie (Frank)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Neuro- und Muskelpathologie (Frank)
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
UniBasel Contributors:Günthert, Ursula and Hirschmann, Petra and Dirnhofer, Stephan and Tzankov, Alexandar
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0301-472X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:06
Deposited On:22 Mar 2012 13:16

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