Saturday, 17 September 2016

Distinguish Between Benign and Malignant Prostate Using the Trace Element Content Ratios in Prostatic Tissue as Tumor Markers


                                                     www.mathewsopenaccess.com



The aim of the study was the development of new highly precise testing methods for early diagnosis of prostate cancer. For this purpose the values of the zinc/silver (Zn/Ag), zinc/cobalt (Zn/Co), zinc/chromium (Zn/Cr), zinc/iron (Zn/Fe), zinc/ mercury (Zn/Hg), zinc/rubidium (Zn/Rb), zinc/antimony (Zn/Sb), zinc/scandium (Zn/Sc), and zinc/selenium (Zn/Se) mass fraction ratios in normal (n = 37), benign hypertrophic (n = 43) and cancerous tissues (n = 60) of the human prostate gland were calculated using data obtained by instrumental neutron activation analysis. Mean values ± standard error of mean (M ± SΕΜ) for trace element mass fraction ratios in normal tissue were: Zn/Ag – 32270 ± 5360, Zn/Co – 27010 ± 3720, Zn/Cr – 2650 ± 360, Zn/Fe – 10.9 ± 1.4, Zn/Hg – 27010 ± 3720, Zn/Rb – 73.6 ± 6.6, Zn/Sb – 34330 ± 6160, Zn/Sc – 46790 ± 7870, and Zn/Se – 1550 ± 170, respectively. It was observed that in benign hypertrophic tissues the Zn/Cr, Zn/ Hg, Zn/Sb, and Zn/Se mass fraction ratios were lower than in normal tissues. In cancerous tissue all investigated mass fraction ratios were significantly (p < 0.001) lower than in normal and benign hypertrophic tissues of the prostate. Finally, we propose to use the estimation of Zn/Ag, Zn/Cr, Zn/Fe, Zn/Hg, and Zn/Sb mass fraction ratios in a needle-biopsy core as an accurate tool to diagnose prostate cancer. Sensitivity, specificity, and accuracy of these tests were in ranges 96-100%, 89-100%, and 94-100%, respectively. Application of the Zn/trace element mass fraction ratios instead the Zn mass fraction is more suitable for PCa diagnosis, because accuracy of Zn/trace element mass fraction ratios does not depend on sample mass and changes in moisture content.


The prostate gland may be a source of many health problems in men past middle age, the most common being benign prostatic hyperplasia (BPH), and prostatic carcinoma (PCa). BPH is a noncancerous enlargement of the prostate gland leading to obstruction of the urethra and can significantly impair quality of life . The prevalence of histological BPH is found in approximately 50-60% of males age 40-50, in over 70% at 60 years old and in greater than 90% of men over 70. In many Western industrialized countries, including North America, PCa is the most frequently diagnosed form of noncutaneous malignancy in males and, except for lung cancer, is the leading cause of death from cancer. Although the etiology of BPH and PCa is unknown, many trace elements have been highlighted in the literature in relation to the development of these prostate diseases. 


Trace elements have essential physiological functions such as maintenance and regulation of cell function and signalling, gene regulation, activation or inhibition of enzymatic reactions, neurotransmission, and regulation of membrane function. Essential or toxic (mutagenic, carcinogenic) properties of trace elements depend on tissue-specific need or tolerance,respectively. Excessive accumulation, deficiency or an imbalance of the trace elements may disturb the cell functions and may result in cellular degeneration, death and malignant transformation.In previous studies significant changes of trace element contents in hyperplastic and cancerous prostate in comparison with those in the normal prostatic tissue were observed. Moreover, a significant informative value of Zn content as a tumor marker for PCa diagnostics was shown. Hence it is possible that besides Zn, some other trace elements also can be used as tumor markers for distinguish between benign and malignant prostate. Current methods applied for measurement of trace element contents in samples of human tissue include a number of methods. Among these methods the instrumental neutron activation analysis with high resolution spectrometry of longlived radionuclides (INAA-LLR) is a non-destructive and one of the most sensitive techniques. It allows measure the trace element contents in a few milligrams tissue without any treatment of sample. Analytical studies of the Ag, Co, Cr, Fe, Hg, Rb, Sb, Sc, Se, and Zn contents in normal, BPH and PCa tissue were done by us using INAA-LLR. Nondestructive method of analysis avoids the possibility of changing the content of chemical elements in the studied samples, which allowed for the first time to obtain reliable results. In particular, it was shown that the average mass fraction of Zn in PCa tissues is 7 times lower than in healthy or BPH tissue. Obtained results formed the basis for a new method for differential diagnosis of BPH and PCa, the essence of which was to determine the content of zinc in the material of trans-rectal needle biopsy of prostate indurated site. For the first time it was proposed to use INAA-LLR to determine zinc and other trace element contents in needle-biopsy cores. 

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