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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4764-4770.
Prepublished online as a Blood First Edition Paper on January 3, 2008; DOI 10.1182/blood-2007-10-115915.
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NEOPLASIA
Clinical quantitation of immune signature in follicular lymphoma by RT-PCR–based gene expression profiling
Richard J. Byers1,
Ebrahim Sakhinia*,2,
Preethi Joseph*,3,
Caroline Glennie3,
Judith A. Hoyland4,
Lia P. Menasce5,
John A. Radford1, and
Timothy Illidge1
1 School of Cancer Imaging Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Manchester;
2 Molecular Diagnostic Centre, Manchester Royal Infirmary, Manchester;
3 Department of Histopathology, Manchester Royal Infirmary, Manchester;
4 Tissue Injury and Repair, School of Clinical and Laboratory Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Manchester; and
5 Department of Histopathology, Christie Hospital National Health Service (NHS) Foundation Trust, Manchester, United Kingdom
Microarray gene expression profiling studies have demonstrated immune response gene signatures that appear predictive of outcome in follicular lymphoma (FL). However, measurement of these marker genes in routine practice remains difficult. We have therefore investigated the immune response in FL using real-time polymerase chain reaction (PCR) to measure expression levels of 35 candidate Indicator genes, selected from microarray studies, to polyA cDNAs prepared from 60 archived human frozen lymph nodes, in parallel with immunohistochemical analysis for CD3, CD4, CD7, CD8, CD10, CD20, CD21, and CD68. High levels of CCR1, a marker of monocyte activation, were associated with a shorter survival interval, and high levels of CD3 with better survival, while immunohistochemistry demonstrated association of high numbers of CD68+ macrophages with a shorter survival interval and of high numbers of CD7+ T cells with a longer survival interval. The results confirm the role of the host immune response in outcome in FL and identify CCR1 as a prognostic indicator and marker of an immune switch between macrophages and a T cell–dominant response. They demonstrate the utility of polyA DNA and real-time PCR for measurement of gene signatures and the applicability of using this type of "molecular block" in clinical practice.
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