Complete loss of PTEN expression as a possible early prognostic marker for prostate cancer metastasis.

The EGF/IGF growth factors are potent mitogens that regulate cell proliferation and cell survival and are involved in prostate cancer development. Using laser microdissection technology and real-time PCR, together with immunohistochemistry, we have explored the growth factor and integrin dependent PI3-kinase/PTEN/Akt signalling pathway in prostate cell lines and tumour samples by analysing EGF-R, IGF1-R, ILK, beta3 integrin, PTEN and p-Akt protein expression. We provide evidence that loss of PTEN expression rather than upregulated EGF/IGF1 receptor expression was responsible for increased p-Akt in neoplastic prostate cells. We therefore compared PTEN expression in patient biopsies at first time diagnosis recruited prospectively (Study I, 112 patients) and patients with confirmed metastasis recruited retrospectively from the Luxembourg cancer registry (Study II, 42 patients). In Study I, loss of PTEN expression at first time diagnosis was found in 26 of 112 patients (23%). In Study II, 25 of the 42 patients (59%) with lymph node metastasis had complete loss of PTEN expression in both the neoplastic glands of the prostate and the invasive prostate cancer cells in the lymph node, and of these 13 (52%) exhibited already loss of PTEN expression at first diagnosis. These findings demonstrate that loss of PTEN expression is an important factor in progression towards metastatic disease and could potentially serve as an early prognostic marker for prostate cancer metastasis

EURL ECVAM Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches (2019)

The European Union Reference Laboratory for alternatives to animal testing (EURL ECVAM) is an integral part of the European Commision's Joint Research Centre. The EURL ECVAM status report informs about research and development activities, test method submissions, validation and peer reviews, activities that promote the regulatory acceptance and international adoption of alternative methods and approaches and their dissemination. Replacement, reduction and refinement of animal testing (Three Rs) in basic, applied and translational research, as well as for regulatory purposes is anchored in EU legislation. Innovative technologies (e.g., computational models, in vitro methods, organ-on-chip devices) are developed, evaluated and integrated in assessment strategies for chemicals and products safety testing in order to preserve a high level of protection for human health and the environment. Important activities to promote the development and use of alternative methods and approaches are also pursued in the areas of basic and applied research as well as for education purposes.JRC.F.3-Chemicals Safety and Alternative Method