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  • Cadherin expression as a biomarker for tumor prognosis in Glioblastoma patients

    Final Number:

    Carolina Noronha MD; Rita Carvalho; Barbara Sousa; Ana Sofia Ribeiro; Ricardo Taipa; Fernando Schmitt; Alfredo Calheiros; Joana Paredes

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2018 Annual Meeting - Late Breaking Science

    Introduction: Glioblastoma is the most frequent malignant primary brain tumor and is still associated with a poor prognosis despite extensive research. Glioblastoma is notorious by its phenotypic diversity and infiltrative behaviour. Cadherins are critical players in a variety of biological mechanisms including tissue morphogenesis as well as tumor invasion/metastasis. N-cadherin expression has been associated to known mechanisms of invasiveness and epithelial-to-mesenchymal transition, while P-cadherin has been shown to be a good marker of stemness. Studies on cadherin expression in both Central Nervous System and gliomas have had heterogeneous results.

    Methods: A surgical series of 180 glioblastoma patients was reviewed regarding clinical, imaging and follow-up data. Pre-operative MRI characteristics were codified according to VASARI (Visually AccesSAble Rembrandt Images) features and diffusion studies. We further evaluated expression for E-cadherin, N-cadherin and P-cadherin and correlated to patient prognosis, neuropathological and imaging characteristics.

    Results: The median overall survival in our series was 12 months. Most tumours expressed N-cadherin, while expression of both E-cadherin and P-cadherin was limited (< 20 %) and correlated to distinct neuropathological and imaging features. Moreover, using cadherin expression profiles we were able to stratify patient prognosis. Individual expression of E-cadherin correlated with a worse prognosis (p=0,015), but strikingly tumors with co-expression Pcad+ Ecad+ predicted the poorest prognosis in our series (p=0.033).

    Conclusions: Expression of P-cadherin and E-cadherin in glioblastoma indicate a distinct tumor subset regarding neuropathological and neuroimaging characteristics, as well as distinct prognosis. We thus propose cadherin expression profiles as disease biomarkers for glioblastoma as they may reflect tumor biological characteristics namely its differentiation, proliferation and invasiveness.

    Patient Care: Our results identify Cadherin expression profiles as biomarkers for survival stratification in glioblastoma and as indicators of tumor biology.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1. Describe the physiological role of cadherin in Central Nervous System and their role in tumour differentiation, proliferation and invasiness. 2. Identify a subset of glioblastoma defined by E-cadherin positivity, with characteristic imaging and neuropathological features. 3. Discuss the potential application of Cadherin expression profiles for glioblastoma prognosis stratification.


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