The aim of our study was to identify early prognostic molecular factors useful in the selection of melanoma patients at higher risk of recurrence/metastasis and to choose adjuvant therapies proper to the molecular alterations. Samples of malignant cutaneous melanoma, from Sardinian and Ecuadorian patients, were immunohistochemically examined for the demonstration of immune system associated antigens (CD8, CD4, HLA-DR, CD68), oncosuppressor (p53, p16), proapoptotic (p53), and antiapoptotic (survivin) proteins, oxidative stress markers (8-hydroxydeoxyguanosine, 8-OHdG), and antioxidant enzymes (DNA-glycosylase 1, OGG1; glucose-6-phosphate dehydrogenase, G6PD). Regarding the immune response, our results indicated that CD8 lymphocytes and HLA-DR cells are both involved in antitumoral activity and can be considered as early prognostic factors. Among proteins involved in the regulation of apoptosis, cell proliferation, and cell cycle, nuclear survivin, p53, and nuclear p16 can be useful as valid individual prognostic markers, although their predictive significance is higher if their expression is considered in combination. Our data also showed that p53 overexpression is coexisting with an intense expression of 8-OHdG and nuclear survivin, suggesting that DNA-oxidative damage, p53 functional loss, and nuclear survivin overexpression may be involved at the same time in the process of melanoma pathogenesis.
Fattori prognostici molecolari nel melanoma cutaneo umano
MURTAS, DANIELA
2008-01-19
Abstract
The aim of our study was to identify early prognostic molecular factors useful in the selection of melanoma patients at higher risk of recurrence/metastasis and to choose adjuvant therapies proper to the molecular alterations. Samples of malignant cutaneous melanoma, from Sardinian and Ecuadorian patients, were immunohistochemically examined for the demonstration of immune system associated antigens (CD8, CD4, HLA-DR, CD68), oncosuppressor (p53, p16), proapoptotic (p53), and antiapoptotic (survivin) proteins, oxidative stress markers (8-hydroxydeoxyguanosine, 8-OHdG), and antioxidant enzymes (DNA-glycosylase 1, OGG1; glucose-6-phosphate dehydrogenase, G6PD). Regarding the immune response, our results indicated that CD8 lymphocytes and HLA-DR cells are both involved in antitumoral activity and can be considered as early prognostic factors. Among proteins involved in the regulation of apoptosis, cell proliferation, and cell cycle, nuclear survivin, p53, and nuclear p16 can be useful as valid individual prognostic markers, although their predictive significance is higher if their expression is considered in combination. Our data also showed that p53 overexpression is coexisting with an intense expression of 8-OHdG and nuclear survivin, suggesting that DNA-oxidative damage, p53 functional loss, and nuclear survivin overexpression may be involved at the same time in the process of melanoma pathogenesis.File | Dimensione | Formato | |
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