Diagnostic, prognostic and predictive immunohistochemistry in malignant melanoma of the skin

Luca Roncati

Abstrakt


Immunohistochemistry (IHC) is an excellent technique for the labeling detection of selected cell proteins, which exploits the principle of antigen-antibody specific binding in biological tissues. First implemented by Albert Coons in 1941, over time it has achieved great success before for diagnostic purposes (diagnostic IHC), then for prognostic ones (prognostic IHC). Several molecular pathways are altered in skin melanoma and non-melanoma skin cancers and some of these can be targeted in oncotherapy. Therefore, a growing field of IHC application has become to predict those tumors which are likely to respond to targeted cancer therapy (predictive IHC), by detecting the presence or high expression levels of altered gene products. Today, the main genes involved in melanoma genesis susceptible to predictive IHC investigation are: BRAF (v-RAF murine sarcoma viral oncogene homolog B), NRAS (Neuroblastoma RAS viral oncogene homolog), CDK4 (Cyclin-Dependent Kinase 4), KIT (tyrosine-protein kinase KIT). More recently, great attention has been paid to melanoma immunotherapy; it is a type of passive immunotherapy aimed to enhance preexisting anti-tumor responses of the organism. My working group has noticed that the best therapeutic results to pembrolizumab, the anti-Pd1 (Programmed cell death protein 1) human monoclonal immunoglobulin G4 capable to block the interaction between Pd1 and Pd-L1 (Programmed death-Ligand 1) favoring the melanoma cell attack by T cells, precisely occur in those patients affected by melanomas with mismatch repair deficiency; therefore, before choosing the most suitable treatment, the bioptic specimen should be also tested for Mlh1 (MutL homolog 1), Msh2 (MutS homolog 2), Msh6 (MutS homolog 6) and Pms1 (PMS1 homolog 1), the well-known DNA mismatch repair proteins in humans.


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