title: Combinations of apoptosis and cell-cycle control biomarkers predict the outcome of human melanoma.
abstract: The deregulation of apoptosis is characteristic of human carcinogenesis. Survivin, an inhibitor of apoptosis, p53 and p16, two tumour suppressor proteins involved in cell cycle control, play a central role in apoptosis. The aim of this study was to investigate, in primary cutaneous melanoma from 68 patients, the expression of survivin with respect to p53 or p16; the association of these proteins, alone or in combination with clinicopathological features; and, most importantly, to elucidate the role of these markers in predicting survival. The level of survivin expression was significantly higher in the p53 positive group of melanomas compared with the p53 negative one, suggesting a cooperative effect in favouring the progression of melanoma, while no correlation was found between survivin and p16. Moreover, the altered expression of nuclear survivin, p53 and p16 were all associated with poor survival, as demonstrated by univariate analysis. However, these biomarkers have been shown to have superior predictive value when studied in combination (P<0.0001) rather than alone, while the risk of mortality grew progressively with increasing the number of altered biomarkers. These data suggest that the assessment of the combined marker status and number of altered markers in patients with melanoma provides important additional prognostic information that may help in patient selection for adjuvant therapies.
authors.affiliation: Department of Cytomorphology, University of Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy. fpiras@unica.it
authors.forename: Franca
authors.initials: F
authors.lastname: Piras
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Perra
authors.forename: Daniela
authors.initials: D
authors.lastname: Murtas
authors.forename: Luigi
authors.initials: L
authors.lastname: Minerba
authors.forename: Carlo
authors.initials: C
authors.lastname: Floris
authors.forename: Cristina
authors.initials: C
authors.lastname: Maxia
authors.forename: Paolo
authors.initials: P
authors.lastname: Demurtas
authors.forename: Jorge
authors.initials: J
authors.lastname: Ugalde
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.forename: Paola
authors.initials: P
authors.lastname: Sirigu
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53