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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1831-1838.
Prepublished online as a Blood First Edition Paper on May 24, 2005; DOI 10.1182/blood-2004-10-3898.
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NEOPLASIA
Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis
Elena Ruiz-Ballesteros,
Manuela Mollejo,
Antonia Rodriguez,
Francisca I. Camacho,
Patrocinio Algara,
Nerea Martinez,
Marina Pollán,
Abel Sanchez-Aguilera,
Javier Menarguez,
Elias Campo,
Pedro Martinez,
Marisol Mateo, and
Miguel A. Piris
From the Department of Genetics and Pathology, Hospital Virgen de la Salud (HVS), Toledo, Spain; the Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain; the Cancer Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain; the Department of Pathology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; and the Department of Pathology, Hospital Clinic, Barcelona, Spain.
Splenic marginal zone lymphoma (SMZL) is a newly recognized lymphoma type whose precise molecular pathogenesis is still essentially unknown. This hampers differential diagnosis with other small B-cell malignancies. With the aim of characterizing this tumor more comprehensively, and of identifying new diagnostic and prognostic markers, we performed cDNA microarray expression profiling and tissue microarray (TMA) immunohistochemical studies in a relatively large series of 44 SMZLs. The results were related to immunoglobulin heavy chain variable region (IgVH) mutational status and clinical outcome. SMZLs display a largely homogenous signature, implying the existence of a single molecular entity. Of the genes deregulated in SMZLs, special mention may be made of the genes involved in B-cell receptor (BCR) signaling, tumor necrosis factor (TNF) signaling and nuclear factor- B (NF-B) activation, such as SYK, BTK, BIRC3, TRAF3, and LTB. Other genes observed were SELL and LPXN, which were highly expressed in spleen, and lymphoma oncogenes, such as ARHH and TCL1. In contrast, the genes CAV1, CAV2, and GNG11 located in 7q31, a commonly deleted area, were down-regulated in the entire series. A comparison with the genes comprising the signature of other small B-cell lymphomas identified 3 genes whose expression distinguishes SMZL, namely ILF1, SENATAXIN, and CD40. Shorter survival was associated with CD38 expression, naive IgVH genes, and the expression of a set of NF-B pathway genes, including TRAF5, REL, and PKCA. (Blood. 2005;106:1831-1838)
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