REVERSE TRANSLATIONAL RESEARCH IN ARCHIVE TISSUES
Dep. Medical Sciences – University of Trieste (Italy)
Molecular pathology can be perceived by many pathologists only as an abstruse field of research with the application of troublesome methods of analysis and with a continuously increasing intrinsic complexity in information. The consequences are a passive application of commercial kits only when a “molecular biomarker” is recognized as an important factor predictive of the success of an expensive biological therapy. We, as pathologists, are acting passively because we are not diffusely testing the validity of the information, not only at the technical level, as it happens with IHC. In the field of molecular analysis our capabilities are often limited and the technologies are not always “mature”. Even worse, in some cases there is the request to send the tissues only to a single specific center for analysis. We must understand that this is not related to pathologists’ inadequacy but to the limits of the methods used and the difficulties of interpretation. We must suspect that the producer is not confident in diffusing a commercial kit, in this way we cannot raise any scientific control and criticism, a very dangerous path for the future of medicine.
All this is still only a very limited part of clinical pathology and we must realize that histology of the lesions has already proved to be strictly related to different molecular pathway alterations and that pathology complexity is mostly connected to tissue heterogeneity, even at the molecular level. For these reasons the contribution of pathologists is essential for a correct development of molecular pathology and medicine. The new molecular knowledge must be harmonized with the huge quantity of data coming from histopathology and IHC. Only pathologists can face this fascinating challenge.
Basic material for this kind of research is constituted by the archive tissues that represent the real clinical heterogeneity. Today we are able to perform any molecular type of analysis in these tissues at the genetic and epigenetic level, at the expression mRNA and protein level and at the non-coding RNA level. We can translate in tissues the knowledge coming from the basic molecular research performed in cell cultures and animal models (translational research), but also obtain new knowledge directly in human pathology and translate this to the basic researchers. This type of applied clinical research is strictly related to tissue pathology and can be defined as “reverse translational research”. Basic researches need many years (ten or more) to be translated into clinical practice, for reverse clinical research the time for application can be shorter, even less than one year to reach the level of a prospective clinical study, e.g. for a predictive biomarker. This is because the patients and the tissues are the same as those used in the research.
These new approaches will open again to the young doctors the fascination of pathology, that has been a little neglected and shadowed in the past decade.
The IMPACTS group has worked in the past years on this issue. This work resulted in the preparation of guidelines for archive tissue molecular analysis, in planning future advanced courses and in the creation of PAT-B Network (www.impactsnetwork.eu
), a virtual bio-banking system network among European pathologists that uses the already existing pathology archives and organized repositories of residual tissues. In this field meetings to discuss the bioethical aspects were also organized. This network is aimed to develop voluntary and direct collaboration among pathologists that are willing to participate in molecular pathology researches even if they are not experienced in molecular methods but just as pathologists collaborating in the project with their case studies and their specific expertise.