Originally published as JCO Early Release 10.1200/JCO.2006.09.4474 on June 18 2007

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Identification of a Proliferation Signature Related to Survival in Nodal Peripheral T-Cell Lymphomas

Marta Cuadros, Sandeep S. Dave, Elaine S. Jaffe, Emiliano Honrado, Roger Milne, Javier Alves, Jose Rodríguez, Magdalena Zajac, Javier Benitez, Louis M. Staudt, Beatriz Martinez-Delgado

From the Human Genetics Group and Genotyping Unit, Spanish National Cancer Centre; Department of Pathology, Hospital La Paz, Madrid; Department of Oncology, Hospital Son Dureta, Palma de Mallorca, Spain; and Lymphoid Malignancies Section and Laboratory of Pathology, National Cancer Institute, Bethesda, MD

Address reprint requests to Beatriz Martinez-Delgado, PhD, Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre, C/. Melchor Fernández Almagro No. 3, 28029, Madrid, Spain; e-mail: bmartinez{at}cnio.es

Purpose Nodal peripheral T-cell lymphomas (PTCLs) constitute a heterogeneous group of neoplasms, suggesting the existence of molecular differences contributing to their histologic and clinical variability. Initial expression profiling studies of T-cell lymphomas have been inconclusive in yielding clinically relevant insights. We applied DNA microarrays to gain insight into the molecular signatures associated with prognosis.

Materials and Methods We analyzed the expression profiles of 35 nodal PTCLs (23 PTCLs unspecified and 12 angioimmunoblastic) using two different microarray platforms, the cDNA microarray developed at the Spanish National Cancer Centre and an oligonucleotide microarray.

Results We identified five clusters of genes, the expression of which varied significantly among the samples. Genes in these clusters seemed to be functionally related to different cellular processes such as proliferation, inflammatory response, and T-cell or B-cell lineages. Regardless of the microarray platform used, overexpression of genes in the proliferation signature was associated significantly with shorter survival of patients. This proliferation signature included genes commonly associated with the cell cycle, such as CCNA, CCNB, TOP2A, and PCNA. Moreover the PTCL proliferation signature showed a statistically significant inverse correlation with clusters of the inflammatory response (P < .0001), as well as with the percentage of CD68⁺ cells.

Conclusion Our findings indicate that proliferation could be an important factor in evaluating nodal PTCL outcome and may help to define a more aggressive phenotype.

published online ahead of print at www.jco.org on June 18, 2007.

Supported by the Comunidad Autonoma de Madrid (Grant No. CAM GR/SAL/0203/2004) and Fondo de Investigación Sanitaria. (Grant No. FIS G03/179). M.C. is a fellow of the Fondo de Investigación Sanitaria.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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• Gene Expression Profiling Does Not Identify Molecular Subgroup Among Nodal Peripheral T-Cell Lymphomas
  Vincenzo Pitini, Carmela Arrigo, and Giuseppe Altavilla
  JCO 2007 25: 4851 [Full Text]

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