Fattori prognostici nel melanoma cutaneo e nel tumore mammario associati a caratteristiche molecolari simil-staminali

Nestin (a neuronal stem cell/progenitor cell marker of central nervous system development), vimentin (which is ubiquitously expressed in mesenchymal cells), and the glucocorticoid receptor (GR, which is involved in the immune response, cell proliferation, and apoptosis) have been shown to interact in embryonic and undifferentiated tissues in modulating cell proliferation. In recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. The aim of this study was to analyse nestin, vimentin and GR expression in tumour tissue (melanoma), and their association with clinicopathological variables, to evaluate any effect on tumour progression. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was also to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients’ outcome. Immunohistochemistry, double label immunofluorescence and confocal laser scanning microscopy were performed on biopsy specimens of cutaneous melanoma from 81 patients and in breast carcinomas from 53 patients. In melanoma, Fisher’s and Pearson’s tests showed a correlation between nestin, vimentin and subcellular GR location (P = 0.008). Their concomitant expression also correlated with Clark level and thickness (P = 0.02 and P = 0.029, respectively). Kaplan–Meier analysis revealed a poorer outcome for stage III and IV patients with associated expression of nestin, vimentin and cytoplasmic GR in tumour tissue (P = 0.02). Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC) subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5 years survival (P=0.02) and with borderline significance at 10-years of survival (P=0.05) in T4 breast cancer patients. These results suggest the presence in melanoma of growth mechanisms involving nestin, vimentin, and GR, similarly to that occurring in embryonic and undifferentiated cells, and may help in understanding tumour biology to provide a molecular basis for clinical therapies. In breast cancer the presence of nestin in tumoral cells and vessels suggest that this protein may be considered an important factor that leads to a poor prognosis. On the basis of these observations, we speculate that the stem cell marker nestin may characterize tumours with an aggressive clinical behavior.