The objectives are devoted to build a very large European virtual tissue bank involving specific European areas in which homogeneous hospital groups work together in order to develop widely applied molecular medicine. These groups are called MEM groups (Molecular Evidence Medicine) and in each group all the hospitals refer to a central laboratory with experience in molecular medicine analysis. The reference molecular pathology laboratories network already exist within the consortium built up by the European project “Archive tissues: improving molecular medicine research and clinical practice –IMPACTS”. These laboratories are already reference points in molecular pathology for the surrounding hospitals. The specific objectives are:
a-Definition of a network of 18 European areas for archive tissue banks related to over 38 million European inhabitants: the Coordination Action “Archive tissues: improving molecular medicine research and clinical practice” is based on 20 participating groups and most of these are important university hospitals that are reference points for the hospitals of their geographic area. In this way it is quite easy to prepare for each group a network of surrounding hospitals participating to the archive tissue banking. Each of these hospitals has at least 20 year-tissue archives that can be used for translational and clinical research. The objective is to cover about 40 million inhabitants of the different European geographic areas with a wide representation of the population across Europe. This virtual tissue bank should contain over 50 million cases with specimens of tissues related to many even rare diseases. One important consideration is that in this collection all the area hospitals are involved, not only the specialized and academic institutions. Indeed, area hospitals perform over 80% of all surgical treatment with the availability of the major part of surgical leftover (collection of surgical leftover frozen and treated with new fixatives preserving proteins; see objective g.).
b-One of the basic objective is to diffuse molecular methods for translational research and clinical practice:there is a bench of data about molecular knowledge in the basic research, but the translation of this to the medical practice is very slow. The idea is to connect the archive tissues bio-banking activity with the diffusion of the molecular medicine methods locally. In this way the participating hospitals will not be only tissues repositories but also centers participating to clinical research and application of the molecular methods. The reference laboratory should diffuse molecular medicine methods within the local hospital group: for this reason it is called Molecular Evidence Medicine (MEM) group. The archive tissues are those tissues which are routinely treated in every hospital. Since today these tissues can be analyzed also at molecular level, this project will enable us to accelerate the clinical application of these methods across Europe and to develop a very powerful system of clinical biomarkers validation.
c-Definition of standards and norms in archive tissue banks: there is an absolute need to develop norms and standards regulating human tissue banks and the access to these tissues for preclinical and clinical research. These should be defined in close collaboration with clinicians who are interested in translational research and clinical application, starting from oncologists and haematologists. This necessity is especially related to multicentric European studies, because of the subsidiarity principle related to bioethics across Europe. There are different rules in each European country and multicentric research on human tissues can sometimes find insuperable obstacles. In France, for example, tissues must always be traceable. For this reason a special permission from the ministry is needed to export tissues outside the country. In this project the organization for international collaborative studies is related to the same MEM group, respecting rules country by country, without abroad transport of tissues. Specific country guidelines will be developed, the research will be carried out inside the country and the results will be finally combined in a general multicentric view. This way is based on a pyramidal structure applicable across Europe.
d-Definition of standards and norms in archive tissue molecular methods: for a clinical application of molecular methods it is necessary to validate and standardize the molecular methods. This is already related to the IMPACTS European project. This project already involves the same reference laboratories network. For this reason the preliminary work which has been done by the IMPACTS project can be directly applied to this project with the completion of the action and the direct application of standards and norms related to the molecular methods. The participating groups are composed by the most experienced European researchers in archive tissue molecular analysis.
e-Organization of a large-scale biomarker discovery and validation system across Europe: many millions of tissue samples are available for molecular large-scale biomarker discovery and clinical validation. For all these archive samples we can obtain a large bench of clinical information and long follow-up periods. In this way, it will be possible to select very well defined and large retrospective case-studies that can be used to validate prognosis, therapy optimization and personalization of biomarkers. The availability of a very large number of cases will also enable us to collect the retrospective tissues in the same way as in the prospective case studies (random collection of the cases without previous follow-up information). Also effective prospective research can be developed with the fixed and paraffin embedded tissues, hospital routinely treated tissues, in an easier way than using a fresh-frozen tissue collection. This type of tissues also allows a more careful micro-dissection before the molecular analysis.
f-Organization of computerized, centralized archives for anonymizedsamples recovery and analysis: for each MEM group a centralized computerized system will be settled down. All the archive tissue samples will be anonymized at the single hospital level and the information will be transducted to the centralized system. In this way a centralized archive will be available to select specific disease cases. There will not be a general tissue archive for all the MEM European groups because of the country specific rules. The European coordination center will prepare the multicentric action on the base of availability of the local case studies and will collect and analyze the final results of the researches.
g-Introduction of proteomics methods in archive tissue bank analysis: new techniques and new fixatives allow a proteomic analysis in archive tissues. The new fixatives can preserve DNA, RNA and proteins. In this way we can have genomics, transcriptomics and proteomics analysis in the same micro-dissected tissues. One of the major interests is that this type of fixation can be the best method also to standardize tissue treatment and this can be done at lower cost than freezing. The proposal is to start this type of fixation in surgical leftover with a diffused bio-banking system related to the same hospitals as those forming the MEM groups. In this way the same level of protein preservation of fresh-frozen tissues can be obtained and proteomics methods can be applied to archive tissues. Formalin-fixed, new fixative-fixed and fresh frozen tissues can be compared in the same cases to validate the results. The objective is to ensure future exploitation for coordinated large-scale biomarker discovery and validation in micro-dissected archive tissues using new proteomics methods. The surgical left-over banking (new fixatives treated and frozen tissues) will be developed and connected with archive tissues clinical cases, in any single hospital.