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H. L. Ramkumar, D. Shen, J. Tuo, J. R. Smith, S. E. Coupland, C.-C. Chan; The IL-10 -1082 SNP and IL-10 and PDCD4 Expression in CNS and Retinal Lymphoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4278.
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Most CNS and retinal B-cell lymphomas produce a high level of interleukin (IL)-10, which has been linked to rapid disease progression and relatively poor prognosis amongst non-Hodgkin lymphoma patients. The IL-10-1082 G allele is associated with improved survival in patients with certain systemic lymphomas. PDCD4 is a tumor suppressor gene and upstream regulator of IL-10. This study examined the correlation between IL-10 SNP, PDCD4 mRNA expression, and IL-10 expression (at transcript and protein levels) in the lymphoma cells.
Archived paraffin-embedded sections of 37 CNS lymphomas with and without retinal lymphoma were obtained. Lymphoma cells were microdissected, and SNP typing was performed on genomic DNA. Expression of IL-10 and PDCD4 mRNA was analyzed by PCR with P32 labeled primer followed by gel separation. Lymphoma cells were microdissected from another 26 cytospin slides of retinal lymphomas, and SNP-typed for IL-10-1082. Vitreous IL-10 and IL-6 levels from these 26 patients were measured. The Wilcoxon signed rank sum test was used for statistical comparison.
Six CNS tumors carrying IL-10-1082 GG had a mean IL-10 mRNA fold level of 0.002, whereas 29 cases carrying IL-10-1082 AG and IL-10-1082 AA had a mean IL-10 mRNA fold level of 9.2 (p<0.05). The vitreous IL-10 (pg/ml) was 724±593 in IL-10-1082 GG patients (n=3) and 1794±603 in IL-10 -1082 AG and IL-10-1082 AA patients (n=21) (p<0.05). The vitreous IL-10/IL-6 ratio was 6.4±2.6 (n=3) in patients with IL-10-1082 GG and 23.5±7.1 (n=21) in patients with IL-10 -1082 AG and IL-10-1082 AA (p<0.05). CNSL patients with IL-10-1082 GG (n=6) had lower PDCD4 expression in their tumor tissue than patients (n=31) with IL-10-1082 AG and IL-10-1082 AA genotypes (p<0.05). No correlation was found between IL-10 and PDCD4 expression levels in 37 CNSL samples.
In CNSL, presence of at least one IL-10-1082A allele results in higher IL-10 mRNA expression in tumor cells. Retinal lymphoma patients with at least one copy of this SNP have a higher vitreal IL-10 level and IL-10/IL-6 ratio. CNSL patients with at least one IL-10-1082 A allele have higher PDCD4 levels, but this may be independent of IL-10 mRNA expression.
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