Tissue micro-environment in molecular pathology

 Research and diagnostics on clinical material is always performed on fixed and paraffin embedded tissues. This aspect makes it necessary to develop molecular techniques in this type of tissues, also called archive tissues. The disadvantage of this analysis is the poor quality of nucleic acid preservation and the advantage is the huge number of samples available in many pathology departments with the possibility to collect any kind of even rare lesion. Availability of a large number of clinical samples makes it easier to analyze tissue heterogeneity in malignant tumours. We have experimental evidence that they are composed by genetically and epigenetically different clones, that can interact functionally. Recent experimental evidence has also shown that there is a phenotypic plasticity at the mRNA and protein level that is often stochastic. This makes it very complex to analyze tumour tissues and gives us account of the extreme variability that we can find when clinical tissues are analyzed. Part of this complexity is also related to the stromal micro-environment that can heavily affect the functional level and phenotypic plasticity. This makes any standardization at the diagnostic level very complex.