Expression of the Chemokine Receptor Gene, CCR8, is Associated With DUSP22 Rearrangements in Anaplastic Large Cell Lymphoma. Issue 8 (September 2015)

• Record Type: Journal Article
• Authors: Xing, Xiaoming; Flotte, Thomas J.; Law, Mark E.; Blahnik, Anthony J.; Chng, Wee-Joo; Huang, Gaofeng; Knudson, Ryan A.; Ketterling, Rhett P.; Porcher, Julie C.; Ansell, Stephen M.; Sidhu, Jagmohan; Dogan, Ahmet; Feldman, Andrew L.
• Is Part Of: Applied immunohistochemistry & molecular morphology. Volume 23:Issue 8(2015)
• Publication Date: 2015-09
• Subjects: Diagnostic immunohistochemistry -- Periodicals; Immunohistochemistry -- Periodicals; Cells -- Morphology -- Periodicals; Molecular diagnosis -- Periodicals; 616.079
• DOI: 10.1097/PAI.0000000000000118
• Languages: English
• ISSNs: 1541-2016

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>Anaplastic large cell lymphoma (ALCL) is one of the most common T-cell non-Hodgkin lymphomas and has 2 main subtypes: an anaplastic lymphoma kinase (ALK)-positive subtype characterized by <italic>ALK</italic> gene rearrangements and an ALK-negative subtype that is poorly understood. We recently identified recurrent rearrangements of the <italic>DUSP22</italic> locus on 6p25.3 in both primary cutaneous and systemic ALK-negative ALCLs. This study aimed to determine the relationship between these rearrangements and expression of the chemokine receptor gene, <italic>CCR8</italic>. CCR8 has skin-homing properties and has been suggested to play a role in limiting extracutaneous spread of primary cutaneous ALCLs. However, overexpression of <italic>CCR8</italic> has also been reported in systemic ALK-negative ALCLs. As available antibodies for CCR8 have shown lack of specificity, we examined <italic>CCR8</italic> expression using quantitative real-time PCR in frozen tissue and RNA in situ hybridization (ISH) in paraffin tissue. Both approaches showed higher <italic>CCR8</italic> expression in ALCLs with <italic>DUSP22</italic> rearrangements than in nonrearranged cases (PCR: 19.5-fold increase, <italic>P</italic>=0.01; ISH: 3.3-fold increase, <italic>P</italic>=0.0008). <italic>CCR8</italic> expression was not associated with cutaneous presentation, cutaneous biopsy site, or cutaneous involvement during the disease course. These findings suggest that <italic>CCR8</italic> expression in ALCL is more closely related to the presence of <italic>DUSP22</italic> rearrangements than to cutaneous involvement and that the function of CCR8 may extend beyond its skin-homing properties in this disease. This study also underscores the utility of RNA-ISH as a paraffin-based method for investigating gene expression when reliable antibodies for immunohistochemical analysis are not available.</p> </sec> </abstract>