• Medientyp: E-Artikel
  • Titel: Abstract 4723: Soluble L1-CAM in the ascites is a prognostic marker in ovarian cancer
  • Beteiligte: Bondong, Sandra; Hielscher, Thomas; Zeimet, Alain; Zeillinger, Robert; Cadron, Isabelle; Sehouli, Jalid; Vergote, Ignace; Mahner, Sven; Speiser, Paul; Braicu, Ioana; Huszar, Monica; Fogel, Mina; Altevogt, Peter
  • Erschienen: American Association for Cancer Research (AACR), 2011
  • Erschienen in: Cancer Research
  • Umfang: 4723-4723
  • Sprache: Englisch
  • DOI: 10.1158/1538-7445.am2011-4723
  • ISSN: 0008-5472; 1538-7445
  • Schlagwörter: Cancer Research ; Oncology
  • Zusammenfassung: <jats:title>Abstract</jats:title> <jats:p>L1-cell adhesion molecule (L1-CAM) is a 200-220 kDa transmembrane protein that belongs to the immunoglobulin superfamily. It was initially found to be expressed on neuronal cells and is involved in axon outgrowth and guidance during central nervous system development. L1-CAM overexpression has been reported for various tumor entities, where it correlates with advanced stage disease, metastasis and chemoresistance. In mouse models, L1-CAM promotes tumor growth and facilitates experimental tumor metastasis. The extracellular part of the full length L1-CAM is subject to membrane proximal cleavage, which generates a soluble form of about 200kDa (sL1-CAM). L1-CAM cleavage and release of the soluble molecule has been shown to promote migration, adhesion and protection from apoptosis of ovarian cancer cells in vitro. The soluble L1-CAM can be detected in body fluids like saliva, serum or ascites.</jats:p> <jats:p>In a multi-centric retrospective study with 270 ovarian cancer patients, we analysed tumor samples to quantify membrane bound full length L1-CAM as well as ascites for sL1-CAM to study the value of L1-CAM as a prognostic marker. We found that L1-CAM expression on the tumor correlated with sL1-CAM in the ascites (rho=0.41). Increased L1-CAM levels on the tumor and in the ascites correlated significantly with a reduced overall survival (univariate p=0.028; 0.022). Elevated ascitic L1-CAM levels were also associated with poor progression free survival (p&amp;lt;0.0001) and remained an independent prognostic marker in multivariate analysis (p=0.0003). Furthermore, increased L1-CAM levels in the ascites correlated with an increased ascites volume (p=0.003). Patients with elevated L1-CAM levels in the tumor were at high risk for incomplete primary debulking (univariate p=0.01, multivariate p=0.04) and had an increased risk for lymph node metastases (p=0.004).</jats:p> <jats:p>Given the in vitro role of L1-CAM in metastasis and invasion in addition to the findings of our study, we conclude that L1-CAM high expressing tumors show a more invasive phenotype which translates into a higher rate of incomplete debulking during upfront surgery. High levels of sL1-CAM in the ascites could serve as a reliable marker for prediction of early relapse and residual tumor burden in women suffering from ovarian cancer.</jats:p> <jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4723. doi:10.1158/1538-7445.AM2011-4723</jats:p>
  • Beschreibung: <jats:title>Abstract</jats:title>
    <jats:p>L1-cell adhesion molecule (L1-CAM) is a 200-220 kDa transmembrane protein that belongs to the immunoglobulin superfamily. It was initially found to be expressed on neuronal cells and is involved in axon outgrowth and guidance during central nervous system development. L1-CAM overexpression has been reported for various tumor entities, where it correlates with advanced stage disease, metastasis and chemoresistance. In mouse models, L1-CAM promotes tumor growth and facilitates experimental tumor metastasis. The extracellular part of the full length L1-CAM is subject to membrane proximal cleavage, which generates a soluble form of about 200kDa (sL1-CAM). L1-CAM cleavage and release of the soluble molecule has been shown to promote migration, adhesion and protection from apoptosis of ovarian cancer cells in vitro. The soluble L1-CAM can be detected in body fluids like saliva, serum or ascites.</jats:p>
    <jats:p>In a multi-centric retrospective study with 270 ovarian cancer patients, we analysed tumor samples to quantify membrane bound full length L1-CAM as well as ascites for sL1-CAM to study the value of L1-CAM as a prognostic marker. We found that L1-CAM expression on the tumor correlated with sL1-CAM in the ascites (rho=0.41). Increased L1-CAM levels on the tumor and in the ascites correlated significantly with a reduced overall survival (univariate p=0.028; 0.022). Elevated ascitic L1-CAM levels were also associated with poor progression free survival (p&amp;lt;0.0001) and remained an independent prognostic marker in multivariate analysis (p=0.0003). Furthermore, increased L1-CAM levels in the ascites correlated with an increased ascites volume (p=0.003). Patients with elevated L1-CAM levels in the tumor were at high risk for incomplete primary debulking (univariate p=0.01, multivariate p=0.04) and had an increased risk for lymph node metastases (p=0.004).</jats:p>
    <jats:p>Given the in vitro role of L1-CAM in metastasis and invasion in addition to the findings of our study, we conclude that L1-CAM high expressing tumors show a more invasive phenotype which translates into a higher rate of incomplete debulking during upfront surgery. High levels of sL1-CAM in the ascites could serve as a reliable marker for prediction of early relapse and residual tumor burden in women suffering from ovarian cancer.</jats:p>
    <jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4723. doi:10.1158/1538-7445.AM2011-4723</jats:p>
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