H Gevensleben1, F Hoellen2, L C Hanker3, A El-Balat4, Z Drosos2, S Kommoss5, T Karn4, U Holtrich4, G Gitas2, M Graeser-Mayer6, M Anglesio7, D Huntsman7, A Rody2. 1. Institute of Pathology, University Hospital Bonn, Bonn, Germany. 2. Department of Gynecology and Obstetrics, University Hospital Luebeck, Luebeck, Germany. 3. Department of Gynecology and Obstetrics, University Hospital Luebeck, Luebeck, Germany. lars.hanker@uni-luebeck.de. 4. Department of Obstetrics and Gynecology, Goethe-University Frankfurt, Frankfurt, Germany. 5. Department of Woman's Health, Tuebingen University Hospital, Tuebingen, Germany. 6. Evangelical Hospital Bethesda, Lower Rhine Breast Center, Moenchengladbach, Germany. 7. Department of Molecular Oncology, BCCA Cancer Research Centre, Vancouver, Canada.
Abstract
PURPOSE: Sphingosine-kinase-1 (SPHK1) is a key enzyme of sphingolipid metabolism which is involved in ovarian cancer pathogenesis, progression and mechanisms of drug resistance. It is overexpressed in a variety of cancer subtypes. We investigated SPHK1 expression as a prognostic factor in epithelial ovarian cancer patients. METHODS: Expression analysis of SPHK1 was performed on formalin-fixed paraffin-embedded tissue from 1005 ovarian cancer patients with different histological subtypes using immunohistochemistry. Staining intensity of positive tumor cells was assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. RESULTS: In our ovarian cancer collective, high levels of SPHK1 expression correlated significantly with complete surgical tumor resection (p = 0.002) and lower FIGO stage (p = 0.04). Progression-free and overall survival were further significantly longer in patients with high-grade serous ovarian cancer and overexpression of SPHK1 (p = 0.002 and p = 0.006, respectively). CONCLUSION: Our data identify high levels of SPHK1 expression as a potential favorable prognostic marker in ovarian cancer patients.
PURPOSE:Sphingosine-kinase-1 (SPHK1) is a key enzyme of sphingolipid metabolism which is involved in ovarian cancer pathogenesis, progression and mechanisms of drug resistance. It is overexpressed in a variety of cancer subtypes. We investigated SPHK1 expression as a prognostic factor in epithelial ovarian cancerpatients. METHODS: Expression analysis of SPHK1 was performed on formalin-fixed paraffin-embedded tissue from 1005 ovarian cancerpatients with different histological subtypes using immunohistochemistry. Staining intensity of positive tumor cells was assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. RESULTS: In our ovarian cancer collective, high levels of SPHK1 expression correlated significantly with complete surgical tumor resection (p = 0.002) and lower FIGO stage (p = 0.04). Progression-free and overall survival were further significantly longer in patients with high-grade serous ovarian cancer and overexpression of SPHK1 (p = 0.002 and p = 0.006, respectively). CONCLUSION: Our data identify high levels of SPHK1 expression as a potential favorable prognostic marker in ovarian cancerpatients.
Authors: Andreas du Bois; Alexander Reuss; Eric Pujade-Lauraine; Philipp Harter; Isabelle Ray-Coquard; Jacobus Pfisterer Journal: Cancer Date: 2009-03-15 Impact factor: 6.860
Authors: Lars Christian Hanker; Thomas Karn; Uwe Holtrich; Regine Gätje; Achim Rody; Tomas Heinrich; Eugen Ruckhäberle; Knut Engels Journal: Int J Gynecol Pathol Date: 2013-05 Impact factor: 2.762
Authors: Ahmed El-Balat; Thomas Karn; Uwe Holtrich; Sven Becker; Stefan Kommoss; Balázs Győrffy; Michael S Anglesio; David G Huntsman; Zacharias Drosos; Achim Rody; Heidrun Gevensleben; Lars C Hanker Journal: Virchows Arch Date: 2020-01-02 Impact factor: 4.064