Xin-Wen Zhang1, Alexander Wald2, Martin Salzmann2, Niels Halama3, Jessica C Hassel2. 1. Department of Oncology and National Center for Tumor Diseases, University of Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. xin-wen.zhang@med.uni-heidelberg.de. 2. Department of Dermatology and National Center for Tumor Diseases, University of Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. 3. Department of Oncology and National Center for Tumor Diseases, University of Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.
Abstract
BACKGROUND: Paraneoplastic leukemoid reaction (PLR) is a rare phenomenon in metastasized melanoma associated with poor prognosis and rapid disease progression. Currently, no specific therapeutic options exist other than treating the underlying malignancy. METHODS: Five cases of paraneoplastic neutrophilia in patients with advanced-stage IV melanoma were enrolled in our study. Cytokine concentrations in patients' serum samples were analyzed before and during PLR using a multiplex cytokine array. Further, immunohistochemical staining of tumor tissue biopsied during PLR was performed. RESULTS AND CONCLUSIONS: We observed a strong correlation between worsening of tumor burden and aggravation of neutrophilia. Cytokine measurements revealed an increase of proinflammatory cytokines (IL6, IFNγ), proangiogenic cytokines (VEGF) and immune stem cell growth factors (G-CSF) during PLR. Immunohistochemistry confirmed neutrophil infiltration of tumor tissue. The presented cytokine alterations provide a basis for further functional analysis, which is necessary for the development of targeted therapeutic approaches against PLR.
BACKGROUND: Paraneoplastic leukemoid reaction (PLR) is a rare phenomenon in metastasized melanoma associated with poor prognosis and rapid disease progression. Currently, no specific therapeutic options exist other than treating the underlying malignancy. METHODS: Five cases of paraneoplastic neutrophilia in patients with advanced-stage IV melanoma were enrolled in our study. Cytokine concentrations in patients' serum samples were analyzed before and during PLR using a multiplex cytokine array. Further, immunohistochemical staining of tumor tissue biopsied during PLR was performed. RESULTS AND CONCLUSIONS: We observed a strong correlation between worsening of tumor burden and aggravation of neutrophilia. Cytokine measurements revealed an increase of proinflammatory cytokines (IL6, IFNγ), proangiogenic cytokines (VEGF) and immune stem cell growth factors (G-CSF) during PLR. Immunohistochemistry confirmed neutrophil infiltration of tumor tissue. The presented cytokine alterations provide a basis for further functional analysis, which is necessary for the development of targeted therapeutic approaches against PLR.
Authors: Jeremy L Davis; R Taylor Ripley; Timothy L Frankel; Irina Maric; Jay N Lozier; Steven A Rosenberg Journal: Melanoma Res Date: 2010-08 Impact factor: 3.599
Authors: Bodo Schniewind; Matthias Christgen; Axel Hauschild; Roland Kurdow; Holger Kalthoff; Hans Jürgen Klomp Journal: Cancer Biol Ther Date: 2005-01-09 Impact factor: 4.742
Authors: Sergei Grivennikov; Eliad Karin; Janos Terzic; Daniel Mucida; Guann-Yi Yu; Sivakumar Vallabhapurapu; Jürgen Scheller; Stefan Rose-John; Hilde Cheroutre; Lars Eckmann; Michael Karin Journal: Cancer Cell Date: 2009-02-03 Impact factor: 31.743