Expression of the chemokine receptor gene, CCR8, is associated with DUSP22 rearrangements in anaplastic large cell lymphoma

Xiaoming Xing, Thomas J Flotte, Mark E. Law, Anthony J. Blahnik, Wee Joo Chng, Gaofeng Huang, Ryan A. Knudson, Rhett P. Ketterling, Julie C. Porcher, Stephen Maxted Ansell, Jagmohan Sidhu, Ahmet Dogan, Andrew L Feldman

Research output: Contribution to journalArticle

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Abstract

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 ALK gene rearrangements and an ALK-negative subtype that is poorly understood. We recently identified recurrent rearrangements of the DUSP22 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, CCR8. CCR8 has skin-homing properties and has been suggested to play a role in limiting extracutaneous spread of primary cutaneous ALCLs. However, overexpression of CCR8 has also been reported in systemic ALK-negative ALCLs. As available antibodies for CCR8 have shown lack of specificity, we examined CCR8 expression using quantitative real-time PCR in frozen tissue and RNA in situ hybridization (ISH) in paraffin tissue. Both approaches showed higher CCR8 expression in ALCLs with DUSP22 rearrangements than in nonrearranged cases (PCR: 19.5-fold increase, P=0.01; ISH: 3.3-fold increase, P=0.0008). CCR8 expression was not associated with cutaneous presentation, cutaneous biopsy site, or cutaneous involvement during the disease course. These findings suggest that CCR8 expression in ALCL is more closely related to the presence of DUSP22 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. ©

Original languageEnglish (US)
Pages (from-to)580-589
Number of pages10
JournalApplied Immunohistochemistry and Molecular Morphology
Volume23
Issue number8
DOIs
StatePublished - Sep 23 2015

Fingerprint

Anaplastic Large-Cell Lymphoma
Chemokine Receptors
Skin
Genes
In Situ Hybridization
Paraffin
RNA
Antibodies
Gene Rearrangement
T-Cell Lymphoma
Non-Hodgkin's Lymphoma
Real-Time Polymerase Chain Reaction
anaplastic lymphoma kinase
Biopsy
Gene Expression
Polymerase Chain Reaction

Keywords

  • anaplastic large cell lymphoma
  • CCR8
  • chemokine receptor
  • RNA in situ hybridization
  • T-cell lymphoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology
  • Histology

Cite this

Expression of the chemokine receptor gene, CCR8, is associated with DUSP22 rearrangements in anaplastic large cell lymphoma. / 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 Maxted; Sidhu, Jagmohan; Dogan, Ahmet; Feldman, Andrew L.

In: Applied Immunohistochemistry and Molecular Morphology, Vol. 23, No. 8, 23.09.2015, p. 580-589.

Research output: Contribution to journalArticle

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 Maxted ; Sidhu, Jagmohan ; Dogan, Ahmet ; Feldman, Andrew L. / Expression of the chemokine receptor gene, CCR8, is associated with DUSP22 rearrangements in anaplastic large cell lymphoma. In: Applied Immunohistochemistry and Molecular Morphology. 2015 ; Vol. 23, No. 8. pp. 580-589.
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AU - Xing, Xiaoming

AU - Flotte, Thomas J

AU - Law, Mark E.

AU - Blahnik, Anthony J.

AU - Chng, Wee Joo

AU - Huang, Gaofeng

AU - Knudson, Ryan A.

AU - Ketterling, Rhett P.

AU - Porcher, Julie C.

AU - Ansell, Stephen Maxted

AU - Sidhu, Jagmohan

AU - Dogan, Ahmet

AU - Feldman, Andrew L

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N2 - 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 ALK gene rearrangements and an ALK-negative subtype that is poorly understood. We recently identified recurrent rearrangements of the DUSP22 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, CCR8. CCR8 has skin-homing properties and has been suggested to play a role in limiting extracutaneous spread of primary cutaneous ALCLs. However, overexpression of CCR8 has also been reported in systemic ALK-negative ALCLs. As available antibodies for CCR8 have shown lack of specificity, we examined CCR8 expression using quantitative real-time PCR in frozen tissue and RNA in situ hybridization (ISH) in paraffin tissue. Both approaches showed higher CCR8 expression in ALCLs with DUSP22 rearrangements than in nonrearranged cases (PCR: 19.5-fold increase, P=0.01; ISH: 3.3-fold increase, P=0.0008). CCR8 expression was not associated with cutaneous presentation, cutaneous biopsy site, or cutaneous involvement during the disease course. These findings suggest that CCR8 expression in ALCL is more closely related to the presence of DUSP22 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. ©

AB - 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 ALK gene rearrangements and an ALK-negative subtype that is poorly understood. We recently identified recurrent rearrangements of the DUSP22 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, CCR8. CCR8 has skin-homing properties and has been suggested to play a role in limiting extracutaneous spread of primary cutaneous ALCLs. However, overexpression of CCR8 has also been reported in systemic ALK-negative ALCLs. As available antibodies for CCR8 have shown lack of specificity, we examined CCR8 expression using quantitative real-time PCR in frozen tissue and RNA in situ hybridization (ISH) in paraffin tissue. Both approaches showed higher CCR8 expression in ALCLs with DUSP22 rearrangements than in nonrearranged cases (PCR: 19.5-fold increase, P=0.01; ISH: 3.3-fold increase, P=0.0008). CCR8 expression was not associated with cutaneous presentation, cutaneous biopsy site, or cutaneous involvement during the disease course. These findings suggest that CCR8 expression in ALCL is more closely related to the presence of DUSP22 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. ©

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KW - CCR8

KW - chemokine receptor

KW - RNA in situ hybridization

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