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Gene Expression Profiling Does Not Identify Molecular Subgroup Among Nodal Peripheral T-Cell Lymphomas

Medical Oncology, University of Messina, Messina, Italy

To the Editor:

In the August 1, 2007, issue of the Journal of Clinical Oncology, Cuadros et al¹ report on the microarray study of 35 nodal peripheral T-cell lymphomas (PTCLs; 23 PTCLs unspecified and 12 angioimmunoblastic T-cell lymphomas [AITLs]) using two different microarray platforms. Although the authors found a proliferation signature in the tumors associated with a shorter survival for patients, they did not observe any association between gene clusters and the histologic subtypes of PTCLs. Furthermore, given the clinical significance of the proliferation signature, which is associated with a high expression of topoisomerase II, they suggest that inhibitors of topoisomerase II, such as doxorubicin are likely to play an important role in this setting. In our opinion there are two key issues that can be underlined. First, WHO classification of PTCLs recognizes three major categories,² two of which are studied by Cuadros et al. AITLs show a distinct morphological and phenotypic pattern whereas unspecified PTCLs are more heterogeneous. So far, microarray analysis has served to refine lymphoma classification by recognizing well-defined lymphoma categories as well as by discovering new entities (eg, activated v germinal center in diffuse large B-cell lymphoma³ or different gene-expression profiles in mantle-cell lymphomas).⁴ In their study, Cuadros et al, using an unsupervised hierarchical clustering analysis, failed to separate unspecified PTCLs from AITLs, so one should assume that currently accepted classification of T-cell lymphoma is wrong and should be deeply revised, even if Ballester et al,⁵ in a similar microarray study, was been able to discriminate AITLs from PTCLs. The second consideration is that doxorubin-based chemotherapy has been the mainstay of therapy for PTCLs, but with the notable exception of anaplastic lymphoma kinase–positive anaplastic large-cell lymphomas, the outcome has been uniformly disappointing, so novel treatment approaches are urgently needed.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Cuadros M, Dave SS, Jaffe ES, et al: Identification of a proliferation signature related to survival in nodal peripheral T-cell lymphomas. J Clin Oncol 25:3321-3329, 2007[Abstract/Free Full Text]

2. Jaffe ES, Harris NL, Stein H, et al: World Health Organisation classification of tumors: Pathology and genetics of tumors of haematopoietic and lymphoid tissues. Lyon, France, IARC Press, 2001[CrossRef][Medline]

3. Rosenwald A, Wright G, Chan WC, et al: The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346:1937-1947, 2002[Abstract/Free Full Text]

4. Kienle D, Katzenberger T, Ott G, et al: Quantitative gene expression deregulation in mantle-cell lymphoma: Correlation with clinical and biologic factors. J Clin Oncol 25:2770-2777, 2007[Abstract/Free Full Text]

5. Ballester B, Ramuz O, Gisselbrecht C, et al: Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas. Oncogene 25:1560-1570, 2006[CrossRef][Medline]

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  Marta Cuadros, Emiliano Honrado, Magdalena Zajac, Javier Benitez, Beatriz Martinez-Delgado, Sandeep S. Dave, Louis M. Staudt, Elaine S. Jaffe, Roger Milne, Javier Alves, and Jose Rodríguez
  JCO 2007 25: 4851-4852 [Full Text]

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• Identification of a Proliferation Signature Related to Survival in Nodal Peripheral T-Cell Lymphomas
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  JCO 2007 25: 3321-3329 [Abstract] [Full Text]

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