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Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma
Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden; Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.ORCID iD: 0000-0002-3384-4387
iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Örebro University, School of Medical Sciences. Department of Laboratory Medicine.ORCID iD: 0000-0001-6881-237X
Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
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2018 (English)In: Biomarker Insights, ISSN 1177-2719, E-ISSN 1177-2719, Vol. 13, article id UNSP 1177271918792246Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explained by cytokine production from the cancer cells.

CASE PRESENTATIONS: A 64-year-old man was referred for hematology workup due to pronounced leukocytosis. While being evaluated for a possible hematologic malignancy as the cause, he was found to have a metastasized renal cell carcinoma, and hyperleukocytosis was classified as a leukemoid reaction. A multiplex panel for measurement of 25 serum cytokines/chemokines showed highly elevated levels of granulocyte colony-stimulating factor (G-CSF) and CXCL8 (C-X-C-motif chemokine ligand 8, previously known as interleukin [IL]-8). By immunohistochemistry it was shown that the renal carcinoma cells expressed both these cytokines. Two additional, consecutive patients with renal cell carcinoma with paraneoplastic leukocytosis also showed elevated serum levels of CXCL8, but not of G-CSF. Nonparametric statistical evaluation showed significantly higher serum concentrations of CXCL8, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor, but lower interferon gamma (IFN-gamma) and IL-1 alpha, for the 3 renal cell carcinoma cases compared with healthy blood donors.

CONCLUSIONS: In suspected paraneoplastic leukocytosis, multiplex serum cytokine analyses may facilitate diagnosis and provide an understanding of the mechanisms for the reaction. In the index patient, combined G-CSF and CXCL8 protein expression by renal carcinoma cells was uniquely documented. A rapidly fatal course was detected in all 3 cases, congruent with the concept that autocrine/paracrine growth signaling in renal carcinoma cells may induce an aggressive tumor phenotype. Immune profiling studies could improve our understanding for possible targets when choosing therapies for patients with metastatic renal cell carcinoma.

Place, publisher, year, edition, pages
Sage Publications, 2018. Vol. 13, article id UNSP 1177271918792246
Keywords [en]
chemokine, IL-6, IL-10, monocytosis, paraneoplastic leukocytosis, autocrine signaling, multiplex, inflammatory response, precision medicine, biomarker
National Category
Immunology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:oru:diva-68648DOI: 10.1177/1177271918792246ISI: 000441829800001PubMedID: 30147294OAI: oai:DiVA.org:oru-68648DiVA, id: diva2:1243874
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-08-31Bibliographically approved

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Åström, MariaKarlsson, Mats G.Lindblad, Per

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