Molecular evaluation of metastatic disease: Why pathology remains (and will remain) mandatory?

Molecular evaluation of metastatic disease: why pathology remains (and will remain) mandatory? Numerous techniques are now available for the molecular evaluation of a tissular or cellular sample in the context of metastatic disease. They include in situ molecular techniques, such as immunohistochemistry for the study of proteins and peptides, in situ hybridization for the study of nucleic acids and in situ cytogenetics (FISH and its variants) for the demonstration of chromosome alterations. They also include all the techniques of molecular biology, which can now be applied to frozen as well as fixed tissue samples. The combination of all these techniques makes it possible an integrated and coherent approach, not limited to the description of DNA abnormalities, but able to correlate genomic alterations with functional, and even structural changes. A second major interest of the analysis of tissue samples is that they make it possible to analyzing not only tumor cells, but also their environment, formed by the stroma and its populations. The study of stroma and of stromal cells, in particular of immune cells, is now of paramount importance for providing new prognostic and predictive biomarkers, especially for anti-angiogenic strategies and for cancer immunotherapy. Tissue analysis is therefore the only way to perform a « total », « phenogenomic » characterization of the tumor as an organ : this is particularly important in the moment in which descriptive genomics is substituted by functional genomics and integrated biology.