IL-10 -1082 SNP and IL-10 in primary CNS and vitreoretinal lymphomas

  • Hema L. Ramkumar
  • De Fen Shen
  • Jingsheng Tuo
  • Rita M. Braziel
  • Sarah E. Coupland
  • Justine R. Smith
  • Chi-Chao Chan
Pathology

Abstract

Objectives

Most primary central nervous system lymphomas (PCNSLs) and primary vitreoretinal lymphomas (PVRLs) are B-cell lymphomas that produce high levels of interleukin (IL)-10, which is linked to rapid disease progression. The IL-10 -1082 G → A polymorphism (IL-10 SNP) is associated with improved survival in certain non-CNS lymphoma patients. PDCD4 is a tumor suppressor gene and upstream regulator of IL-10. This study examined the correlation between the IL-10 SNP, PDCD4 mRNA expression, and IL-10 expression (at transcript and protein levels) in these lymphoma cells.

Materials and methods

Single-nucleotide polymorphism (SNP)-typing at IL-10 -1082 was performed after microdissecting cytospun PVRL cells from 26 specimens. Vitreal IL-10 and IL-6 levels were measured by ELISA. PCNSL cells from 52 paraffin-embedded sections were microdissected and SNP typed on genomic DNA. RT-PCR was performed to analyze expression of IL-10 and PDCD4 mRNA. IL-10 -1082 SNP typing was performed on blood samples of 96 healthy controls. We measured IL-10 -1082 SNP expression in 26 PVRLs and 52 PCNSLs and examined its relationship with IL-10 protein and gene expression, respectively.

Results

More PVRL patients expressed one copy of the IL-10 -1082 G → A SNP with the GA genotype compared to controls. The frequencies of the three genotypes (AA, AG, GG) significantly differed in PVRL versus controls and in PCNSL versus controls. In PVRLs, the vitreal IL-10/IL-6 ratio was higher in IL-10 -1082 AG and IL-10 -1082 AA patients, compared to IL-10 -1082 GG patients. IL-10 mRNA expression was higher in IL-10 -1082 AG and IL-10 -1082 AA PCNSLs, compared to IL-10 -1082 GG PCNSLs. No correlation was found between IL-10 and PDCD4 expression levels in 37 PCNSL samples.

Conclusions

PVRL and PCNSL patients had similar IL-10 -1082 A allele frequencies, but genotype distributions differed from healthy controls. The findings suggest that the IL-10 -1082 A allele is a risk factor for higher IL-10 levels in PVRLs and PCNSLs. Higher IL-10 levels have been correlated with more aggressive disease in both PVRLs and PCNSLs, making this finding an important and potentially clinically significant observation.

Keywords

Primary vitreoretinal lymphoma Primary CNS lymphoma Interleukin-10 Single-nucleotide polymorphism PDCD4 (program cell death 4) 

Notes

Acknowledgments

We would like to thank the National Eye Institute Intramural Research Program, Howard Hughes Medical Institute, Research to Prevent Blindness’s unrestricted grant to Casey Eye Institute, the Schnitzer-Novack Foundation, and the Eye Tumour Research Fund for financial support. We thank Dr. Nussenblatt and the NEI clinical fellows for the contribution of their patients’ vitreous specimen to this study. We also appreciate the physicians from other institutions who provided vitreous specimens.

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer-Verlag (outside the USA) 2012

Authors and Affiliations

  • Hema L. Ramkumar
    • 1
    • 2
  • De Fen Shen
    • 1
  • Jingsheng Tuo
    • 1
  • Rita M. Braziel
    • 3
  • Sarah E. Coupland
    • 5
  • Justine R. Smith
    • 4
  • Chi-Chao Chan
    • 1
  1. 1.Immunopathology SectionLaboratory of Immunology National Institutes of HealthBethesdaUSA
  2. 2.Howard Hughes Medical InstituteChevy ChaseUSA
  3. 3.Department of Surgical PathologyOregon Health & Science UniversityPortlandUSA
  4. 4.Casey Eye Institute & Department of Cell & Developmental BiologyOregon Health & Science UniversityPortlandUSA
  5. 5.Department of Cellular & Molecular PathologyUniversity of LiverpoolLiverpoolUK

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