Although recognised as essential to induce cervical cancer, infection by oncogenic HPV is not per se sufficient to lead to tumour development. Epidemiological evidences indicate that the vast majority of cervical lesions would regress spontaneously, while a small proportion of those expressing E6/E7 oncoproteins would have the potential to progress towards cancer. Since it is not possible to certainty predict the clinical outcome of a single HPV infection, all cervical lesions have to be regarded as potentially progressing. Thus, they often undergo overtreatment. The immunomodulatory role of trace elements as well as their influence on the outcome of many viral infection are widely recognized. Changes in serum levels of trace metals have been also observed in some neoplasia, thus postulating their role during carcinogenesis and cancer progression. Trace elements would also act as cofactors of antioxidant enzyme, which protects body from damage by oxidative stress (OS) that has a key role in several degenerative processes, including cancer. Based on this background, we firstly assessed the level of trace elements on a set of normal, dysplastic (E6/E7 mRNA positive) and neoplastic cervical samples. Further, we tentatively assessed the correlation with the expression of OS response proteins.
Trace elements were analysed on cytologic samples by Inductively Coupled Plasma Mass Spectrometry. On the corresponding tissue samples, expression pattern of OS associated proteins (CuZn Superoxide Dismutase 1/2-SOD1/SOD2, Thioredoxin Reductase2-TrxR2, Glutathione Transferase1-GSTP1) were investigated by immunohystochemistry. One-way ANOVA followed by Fisher LSD post-hoc test was performed to test for differences in elements concentration and proteins expression. p-values less than 0.05 were considered as statistically significant.
Copper (Cu) level showed a trend to higher levels starting from negative to dysplastic groups. Then, it declined in neoplasia (p<0.001). Zinc levels paralleled Cu concentrations, but this trend did not reached statistical significance. TrxR2 significantly increased its expression in dysplastic and neoplastic tissue, as compared with control. This trend was also observed for SOD1 and SOD2. GSTP1 shows an growing trend too, but its level fell in neoplastic tissue
Change in copper levels seems to be associated with increased oxidant milieu, which would provide the condition for neoplastic progression. Although further studies are needed, a better understanding of interdependence between stress protein markers and trace elements may provide further insights into the mechanisms involved in cervical carcinogenesis.
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