Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma

Abstract

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-γ) and IL-1α, 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.

<p>ITPKA1 Promotes Growth, Migration and Invasion of Renal Cell Carcinoma via Activation of mTOR Signaling Pathway</p>

“…Combined with the survival analysis ( http://gepia.cancer-pku.cn/index.html ), 11 genes exhibited significant clinical outcome and accorded with the malignancy of the genes. Among the 11 significant DEGs, 4 genes, such as AIM2, 14 IGF2BP3, 15 CXCL13 16 and IL20RB 17 had been demonstrated to play critical roles related to the development of RCC. The other 7 genes had not been reported to be associated with RCC growth and progression.…”

VHL Ser65 mutations enhance HIF2α signaling and promote epithelial-mesenchymal transition of renal cancer cells

“…While having stringent DE analysis (DEseq; FDR < 0.05, fold change > 2), we revealed a higher number of upregulated (n = 148) compared with downregulated genes (n = 46) under the expression of VHL-S65P, and upregulated (n = 248) compared with downregulated genes (n = 142) under the expression of VHL-S65W, suggestive of gain of function mutations in VHL stabilizing HIF2α. Among the most altered genes, it has been shown that renal cancer progression can be promoted by upregulation of CXCL8 [ 23 ], ADAM9 [ 24 ], NDRG1 [ 25 ], SOD2 [ 26 ], SREBF1 and SREBF2 genes [ 27 ]. The genes NDRG1 [ 25 ] and SREBF2 [ 27 ] have also been reported as potential prognostic biomarkers for RCC, and SREBF1/2 were found to play roles in regulating lipid metabolism and have effects on ccRCC growth and survival.…”

Leukemoid reaction with severe thrombocytopenia in a dying patient: a case report and literature review

“…Two retrospective studies have shown that most leukemoid reactions are caused by solid tumours, 3 , 4 and the abnormal increase in WBC count may be caused by abnormal secretion by tumour cells. 5 Other non-tumour causes include infection, a side-effect of corticosteroid treatment or haematopoietic growth factors, severe haemorrhage, and bone metastases with necrosis. In clinical settings, a common dilemma has been the differential diagnosis between tumour and infection.…”