Nuclear 8-hydroxy-2'-deoxyguanosine as survival biomarker in patients with cutaneous melanoma.
8-hydroxy-2'-deoxyguanosine (8-OHdG) is one of the main mutagenic modifications induced in DNA by oxidative stress. Elevated levels of 8-OHdG have been regarded as an independent prognostic factor in different types of cancer. Various enzymes, such as human 8-oxoguanine DNA-glycosylase 1 (hOGG1) and glucose-6-phosphate dehydrogenase (G6PD), act as protection against oxidative stress. The low activity of such enzymes has been consistently associated with increased risk of progression in several tumor types. The aim of this study was to investigate whether 8-OHdG, hOGG1 and G6PD expression in tumor tissues might be a predictor of survival in melanoma patients. The expression of 8-OHdG, hOGG1 and G6PD was immunohistochemically investigated in primary cutaneous melanoma and the effect on survival was analyzed. Furthermore, the immunostaining for p53 and survivin was evaluated and the relationship among 8-OHdG, hOGG1, G6PD, p53 and survivin expression was analyzed. Kaplan-Meier analysis demonstrated that patients with low expression of nuclear 8-OHdG had significantly longer survival time compared with those with a high expression (P=0.032), whereas cancer-specific survival of patients was not associated with hOGG1 or G6PD expression. These results suggest an involvement of oxidative DNA damage in the process of melanoma pathogenesis and demonstrate that 8-OHdG expression in nuclei of tumor cells could be useful as an early independent prognostic marker in patients with primary cutaneous melanoma.
Murtas
Daniela
D
Department of Cytomorphology, University of Cagliari, Italy Cittadella Universitaria, 09042 Monserrato (CA), Italy.
Piras
Franca
F
Minerba
Luigi
L
Ugalde
Jorge
J
Floris
Carlo
C
Maxia
Cristina
C
Demurtas
Paolo
P
Perra
Maria Teresa
MT
Sirigu
Paola
P
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D008875:Middle Aged; D011379:Prognosis; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D016019:Survival Analysis; D055815:Young Adult
D014408:Biomarkers, Tumor; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine