In the last two decades we have witnessed a revolutionary development in molecular biology and genetics. This new knowledge seems to be very important for medicine in general, as we have obtained a very important base of scientific facts to apply to clinical practice. These advances have the potential to change this practice in a way that no other technique ever had before. Since the clinical applications of these new data are still slowly evolving, we must accelerate the process and demonstrate its beneficial consequences for a wider range of patients. Emerging capabilities have been introduced in a personalized medicine with individual risk assessment and best-suited care. To reach these goals, the most difficult task is to recognize right biomarkers in the right case study. Today most of the molecular research is carried out on cell culture and animal models, but it is also possible to apply it directly to human clinical tissues. This allows developing a "Reverse Translational Research" (bedside to bench) that can accelerate the process of molecular medicine clinical application.
A very important tool for translational research is represented by the large number of human archive tissues (AT) stored in hospitals all over Europe. Tissue specimens removed from patients for diagnosis or surgical therapy are fixed and paraffin-embedded in order to obtain a conclusive diagnosis. After few sections are cut for a histopathological examination, all these blocks of tissues are often stored in archives for many decades. It is estimated that every year 30 million new cases are collected in the European hospitals and that the total number of specimens could be around 100 million.
We already have the technology that allows molecular research at the DNA and RNA level on fixed and paraffin embedded tissues and new possibilities for proteomics analysis are emerging. In Europe many laboratories are working with archive tissues at the molecular level. DNA genomic analysis is already widely spread in research and diagnostics (see lymphomas and leukaemia etc.). Less diffused and validated are the techniques to study DNA methylation, loss of heterozigosity (LOH) or single nucleotide polymorphisms (SNP) in archive tissues. Many laboratories also perform analysis at the RNA level in order to detect RNA virus persistence or to study gene expression for functional genomics, micro-RNAs and other non-coding RNAs. These methods for RNA qualitative and quantitative analysis in archive tissues were first developed by the European scientists who are involved in the IMPACTS group. Today these methods for molecular analysis in human tissues are used everywhere in the world. Recently some experience in expression microarrays in AT has also been developed. Protein expression in archive tissues can be studied by immunohistochemistry and tissue arrays, but also by protein extraction as recently shown by the European scientists involved in the action, directly in formalin-fixed tissues or in tissues fixed by new rapid procedures.
A very important aspect to be tackled to use archive human tissues for research is bioethics. Every European country has more or less developed ethical rules that should also be applied to archive human tissues. However we have sometimes no direct rules to apply concerning this issue. There is urgent need to give a general frame of bioethical behaviour to scientists and clinicians working with human tissues, as already studied and reported at the European level. This is a very complex matter that needs a transdisciplinary approach, since the question at the European level is also related to the so-called “subsidiarity principle” of the European Union, as compared to the country-specific rules. Researches from clinical residual archive tissues can be applied to patients in a very short time, because they are performed in the same type of tissues as the clinical routine tissues. This time can be so short that the same donor patient could also be the recipient of the benefits of the research. The use of these tissues in the clinical trials can also help to reduce the complexity and the costs. The advantages that any patient can obtain from their clinical tissues are a correct diagnosis and profitable research.
The Coordination Action proposal starts from a large group of European pathologists from 11 countries, who have found within the European Society of Pathology the nucleus of a long discussion about AT potentiality in human pathology research. This group of pathologists include some of the most excellent pathologists in Europe, who have recognized the importance to use AT to speed up research and clinical applications in molecular pathology and medicine.