May the level and ratio changes of trace elements be utilized in identification of disease progression and grade in prostatic cancer?

Abstract

Objective: The effects of the level and ratio changes in the trace elements have been reported previously in several diseases. The aim of this study was to determine whether those trace elements (Cu, Fe and Zn) can be used to distinguish among different histology grades of prostate cancer development and progression, and to assess the level changes of trace elements in serum and in tissues and copper-to-zinc and iron-to-zinc ratios in the serum and prostatic tissues of patients. Material and methods: 69 patients comprised of 23 patients with benign prostatic hypertrophy (BPH), 20 patients with malignant prostatic carcinoma (Malign Ca), 14 patients with low-grade prostatic intraepithelial neoplasia (LGPIN) and 12 patients with high grade prostatic intraepithelial neoplasia (HGPIN) diagnosed on basis of clinical profile, transrectal ultrasonography (TRUS) and histopathology, were included in this study. The levels of elements were determined by atomic absorption spectrophotometer. Results: The mean serum Cu levels in malign Ca were significantly higher than those seen in LGPIN, in HGPIN, and controls (p<0.001, p<0.01, p<0.001, respectively). The mean serum Cu/Zn ratios in malign Ca were significantly higher than those in BPH (p < 0.01), LGPIN (p < 0.01), HGPIN (p < 0.01), and controls (p<0.001). However, the mean serum Fe levels in controls were significantly lower than those in BPH, malign Ca, LGPIN and HGPIN (p<0.001 for each). The mean serum Fe/Zn ratio in controls were significantly lower than those in malign Ca and LGPIN (p < 0.001 for each). The mean tissue Cu levels in malign Ca were significantly higher than those in LGPIN (p < 0.01) and HGPIN (p < 0.05). However, the tissue Zn levels of malign Ca were significantly lower than those of BPH (p < 0.05), but similarly these differences were not statistically significant among malign Ca, LGPIN and HGPIN. The mean tissue Fe concentrations were significantly lower in LGPIN as compared to HGPIN (p<0.05). From Pearson correlation analysis, there were significant positive correlations between Cu/Zn and Fe/Zn ratios in serum, Fe/Zn in serum and Fe/Zn in tissue in HGPIN (r = 0.636, p < 0.05; r = 0.776, p < 0.01, respectively). Serum Cu/Zn was significantly positively correlated with serum Fe/Zn, tissue Cu/Zn and tissue Fe/Zn in malign Ca (r = 0.527, p < 0.05; r = 0.685, p < 0.01; r = 0.556, p<0.05, respectively). A significant positive correlation was also found between tissue Cu/Zn and tissue Fe/Zn in malign Ca (r = 0.639, p<0.01). Moreover, there was a significant positive correlation between serum Cu/Zn ratio and tissue Fe/Zn ratio in LGPIN (r = 0.755, p<0.01). However, there was a negativ correlation between tissue Cu/Zn ratio and serum Fe/Zn ratio in LG PIN (r = -0.695, p < 0.01). Conclusion: These findings indicate that changes of levels of Cu, Zn and Fe, and Cu/Zn and Fe/Zn ratios in the serum and/or tissue are influenced by the prostatic carcinoma development and progression. Therefore, further studies need to be performed to clarify the exact role of these disparities of trace elements that are rooted from and are affected by tumorigenesis or by the result of tumorigenesis.