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Prostate cancer outcome and tissue levels of metal ions
Conference presentation

Prostate cancer outcome and tissue levels of metal ions

A Sarafanov, T Todorov, J Centeno, V Macias, W Gao, W M Liang, C Beam, Marion Gray and A Kajdacsy-Balla
Annual Meeting of the American Association for Cancer Research: Science, Synergy and Success, 100th (Denver, United States, 18-Apr-2009–22-Apr-2009)
2009
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Abstract

Clinical Sciences Oncology and Carcinogenesis state paraffin-embedded tissue ICP-MS trace metals
Background: There are many studies on prostate cancer incidence and exposure to heavy metals such as cadmium, iron, selenium and zinc. Much less data is available on the possible influence of heavy metals on prostate cancer outcome. We and others have shown that cadmium, iron and zinc exposure in vitro can cause changes in cell invasion. Recently we have published an inductively coupled plasma-mass spectrometry (ICP-MS) method to reliably measure concentration of these metals in paraffin embedded archival tissues. Here we study the level of these ions in the prostate of patients with known outcome in order to address metals and disease progression. Methods: The source of tissues Cooperative Prostate Cancer Tissue Resource (CPCTR). We obtained formalin fixed paraffin embedded tissue blocks of prostatectomy samples of 40 patients with PSA recurrence, matched 1:1 (for year of surgery, race, age, Gleason grading score and stage) with tissue blocks from 40 patients without recurrence (n=80). All non-recurrence patients had more than 5-years post-prostatectomy follow-up. Case-control pairs were compared for the levels of heavy metals in areas adjacent to tumors. After deparaffinization, each tissue sample was oven-dried and divided in 5-10 µg triplicates. Internal standards were added (Y and 74Se), digested overnight in nitric acid. ICP-MS was performed by comparing samples with standard solutions of each analyte (Cd, Fe, Zn, and Se). The association of each individual metal with prostate cancer recurrence was evaluated by Wilcoxon signed rank paired test comparing matched recurrence cases and non-recurrence control cases. Results: Patients with biochemical (PSA) recurrence of disease had 14% lower iron [95 vs. 112 parts per million (ppm); p = 0.04] and 9% lower zinc (28 vs. 35 ppm; p = 0.04) concentrations in the normal-appearing tissue immediately adjacent to prostate cancer areas. Differences in cadmium [488 vs. 439 parts per billion (ppb); 10% higher) and selenium (1676 vs. 1576 ppb; 6% higher] levels were not statistically significant in recurrence cases when compared to non-recurrences (p=0.40 and 0.21 respectively). Discussion: To the best of our knowledge this is the first study to show an association between metal tissue levels and outcomes in prostate cancer. Lower zinc in cases of worse outcome suggests this may be an area for further investigation in recurrence chemoprevention. Lower iron may be the result of iron sequestration in the reticuloendothelial system caused by aggressive cancer, rather than a factor important for prostate cancer progression, a hypothesis that needs further investigation. The lack of association of recurrence with either cadmium or selenium was an unexpected finding.

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