Molecular prognostic markers and epigenetic control in tumors of the skin and the head and neck region

The factor increasingly recognized as contributing to all aspects of cancer behavior is epigenetics, that is, changes in gene expression without the alterations of the DNA sequence. Most important epigenetic processes are methylation and histone modifications, which, in cancer cells, affect pathways involved in cell cycle progression, apoptosis, telomere maintenance, DNA repair and cell adhesion. Interference with epigenetic misregulation through enzyme inhibition has achievable therapeutic potential. Determination of an epigenetic profile of each individual tumor should be the preceding step before the appliance of such therapy. We plan to perform immunohistochemical (and to selected cases genetical) analysis of skin and the head and neck tumors, including the in situ, invasive and metastatic lesions and to correlate the results with various clinical and histological prognostic parameters. Investigation would be performed on tissue microarrays constructed from the large archive of surgical samples, using different immunostaining evaluation approaches (distribution of positive cells, semiquantitative estimation of the percentage of positive cells, labelling index) for every tumor. That should provide the information about the epigenetic profile (still scarce for the most skin and the head and neck cancers) and the approprate method of the immunostaining estimation that would allow selection of cases suitable for the epigenetic therapy.