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Distinguishing malignant from benign prostate using Br, Ca, K, Mg, Mn, and Na content in prostatic tissue

Vladimir Zaichick

Radionuclide Diagnostics DepartmentMedical Radiological Research Centre Koroleva Str.- 4, Obninsk 249036 Kaluga Region, Russia

E-mail : vezai@obninsk.com

Sofia Zaichick

Department of Medicine University of Illinois College of Medicine Chicago, IL 60612, USA

DOI: 10.15761/IMM.1000234.

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Abstract

Contents of Br, Ca, K, Mg, Mn, and Na in normal (n=37), benign hypertrophic (n=27) and cancerous tissues (n=23) of the human prostate gland were investigated by non-destructive instrumental neutron activation analysis with high resolution spectrometry of short-lived radionuclides (INAA-SLR). Mean values ± standard error of mean (M ± SΕΜ) for mass fraction (mg/kg on dry mass basis) of chemical element in the normal tissue were as follows: Br 32.9 ± 3.6, Ca 2280 ± 178, K 11211 ± 414, Mg 1118 ± 76, Mn 1.24 ± 0.07, and Na 11100 ± 408, respectively. It was observed that in benign hypertrophic tissues the levels of Br, Ca, Mg, Mn, and Na were equal to those in normal prostate tissues while the level of K was significantly higher. By contrast, the levels Ca, Mg, K, and Na were significantly lower and those of Br and Mn were significantly higher in cancerous tissues than in normal and BPH tissues. The Br, Ca, Mg, and Mn mass fractions were the most informative indicators for distinguishing malignant from benign prostate with sensitivity, specificity, and accuracy in the ranges 91-100%, 92-100%, and 93-100%, respectively. Obtained data allowed us to adequately evaluate the importance of chemical element content for the diagnosis of prostate cancer.

Key words

chemical elements, prostate, benign prostatic hypertrophy, prostatic carcinoma, neutron activation analysis

Introduction

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 [1]. 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 [2,3]. 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 [49]. Although the etiology of BPH and PCa is unknown, some electrolytes and trace elements have been highlighted in the literature in relation to the development of these prostate diseases [10-29].

Electrolytes and 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 chemical elements depend on tissue-specific need or tolerance, respectively [30]. Excessive accumulation, deficiency or an imbalance of the chemical elements may disturb the cell functions and may result in cellular degeneration, death and malignant transformation [31].

In reported studies significant changes of chemical element contents in hyperplastic and cancerous prostate in comparison with those in the normal prostatic tissue were observed [32-56]. Moreover, a significant informative value of Zn content as a tumor marker for PCa diagnostics was shown by us [57,58]. Hence it is possible that besides Zn, some other chemical elements also can be used as tumor markers for distinguish between benign and malignant prostate.

Current methods applied for measurement of chemical 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 short-lived radionuclides (INAA-SLR) is a non-destructive and one of the most sensitive techniques. It allows measure the chemical element contents in a few milligrams tissue without any treatment of sample. Analytical studies of the Br, Ca, K, Mg, Mn, and Na contents in normal, BPH and PCa tissue were done by us using INAA-SLR [15,21,28,50,55]. Nondestructive method of analysis avoids the possibility of changing the content of chemical elements in the studied samples [59-62], which allowed for the first time to obtain reliable results. In particular, it was shown that the average mass fraction of Ca in BPH tissue does not differ from normal level [54], but in PCa tissues it is 3.4 times lower than in healthy prostatic tissue [50]. 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 Ca in the material of transrectal needle biopsy of prostate indurated site.

Therefore, the present study had three aims. The main objective was to assess the Br, Ca, K, Mg, Mn, and Na contents in intact prostate of healthy men aged over 40 years and in the prostate gland of age-matched patients, who had either BPH or PCa using INAA-SLR analysis. The second aim was to compare the levels of chemical elements in normal, hyperplastic, and cancerous prostate, and the third aim was to evaluate the chemical element content for diagnosis of prostate cancer.

All studies were approved by the Ethical Committees of the Medical Radiological Research Centre, Obninsk.

Material and methods

 Samples

All patients studied (n=50) were hospitalized in the Urological Department of the Medical Radiological Research Centre. Transrectal puncture biopsy of suspicious indurated regions of the prostate was performed for every patient, to permit morphological study of prostatic tissue at these sites and to estimate their chemical element contents. In all cases the diagnosis has been confirmed by clinical and morphological results obtained during studies of biopsy and resected materials. The age of 27 patients with BPH ranged from 56 to 78 years, the mean being 67.3 ± 5.6 (M ± SD) years. The 23 patients aged 51-78 suffered from PCa. Their mean age was 67.3 ± 8.6 (M ± SD) years.

Intact (Norm) prostates were removed at necropsy from 37 men aged 41-79 who had died suddenly. Their mean age was 55 ± 11 (M ± SD) years. The majority of deaths were due to trauma. Tissue samples were collected from the peripheral zone of dorsal and lateral lobes of their prostates, within 2 days of death and then the samples were divided into two portions. One was used for morphological study while the other was intended for chemical element analysis. A histological examination was used to control the age norm conformity, as well as to confirm the absence of microadenomatosis and latent cancer [15,21,28].

4Sample preparation, instrumentation, methods and certified reference materials

Details of sample preparation, the relevant nuclear reactions, radionuclides, gamma energies, methods of analysis and the results of quality control were presented in our earlier publications concerning the chemical elements of human prostate tissue investigated by INAA-SLR [15,21,28,50,55,63].

Computer programs and statistic

A dedicated computer program for INAA mode optimization was used [64]. All prostate samples for INAA-SLR were prepared in duplicate and mean values of chemical element contents were used in final calculation. Using the Microsoft Office Excel software, the summary of statistics, arithmetic mean, standard deviation, standard error of mean, minimum and maximum values, median, percentiles with 0.025 and 0.975 levels was calculated for chemical element mass fraction in normal, benign hyperplastic and cancerous prostate tissue. The difference in the results between BPH and Norm, PCa and Norm, and PCA and BPH was evaluated by Student’s t-test. For the construction of “individual data sets for Br, Ca, K, Mg, Mn, and Na mass fraction n normal, benign hypertrophic and cancerous prostate” diagrams the Microsoft Office Excel software was also used.

Results

Table 1 depicts our data for six chemical elements in ten sub- samples of certified reference material (CRM) IAEA H-4 (animal muscle) and the certified values of this material.

Table 1. NAA-SLR data of chemical element contents in reference material IAEA H-4 (animal muscle) compared to certified values (mg/kg, dry mass basis)

Element

 

IAEA H-4 (animal muscle)

 

This work results

 

95% confidence interval

 

Mean ± SD

Br

 

3.5 – 4.7a

 

5.0 ± 0.9

Ca

 

163 – 213a

 

238 ± 59

K

 

15300 – 16400a

 

16200 ± 3800

Mg

 

990 – 1110a

 

1100 ± 190

Mn

 

0.48 – 0.55b

 

0.55 ± 0.11

Na

 

1930 – 2180a

 

2190 ± 140

Mean – arithmetical mean, SD – standard deviation, a- certified values, b – non-certified values.

Table 2 presents certain statistical parameters (arithmetic mean, standard deviation, standard error of mean, minimal and maximal values, median, percentiles with 0.025 and 0.975 levels) of the Br, Ca, K, Mg, Mn, and Na mass fractions in normal, benign hypertrophic and cancerous prostate.

Table 2. Some statistical parameters of Br, Ca, K, Mg, Mn, and Na mass fractions (mg/kg, dry mass basis) in normal, benign hyperplastic (BPH), and cancerous (PCa) prostate

Tissue

Parameter

Mean

SD

SEM

Min

Max

Median

P 0.025

P 0.975

Normal

Br

32.9

17.7

3.6

12.5

80.7

28.2

12.6

70.9

n=37

Ca

2280

874

178

1205

4908

2082

1340

4386

K

11211

2071

414

7100

14328

11399

7100

13998

Mg

1118

396

76

604

2060

1062

626

1963

Mn

1.24

0.32

0.07

0.40

1.80

1.30

0.65

1.75

Na

11100

2159

408

6834

15300

11071

6879

15161

BPH

Br

30.4

18.4

3.6

5.5

77

25.6

5.75

66.7

n=27

Ca

2032

547

165

1168

2762

1898

1173

2757

K

14472

2454

740

11683

20519

13552

12025

19744

Mg

1201

276

83

687

1585

1263

749

1552

Mn

1.19

0.31

0.09

0.80

1.80

1.20

0.80

1.73

Na

11612

2882

869

7762

15503

10564

7893

15400

PCa

Br

115

45

9.5

11.3

193

115

13.1

184

n=23

Ca

674

193

58

382

952

751

411

931

K

8542

1672

504

6047

11833

8784

6270

11402

Mg

346

193

61

136

632

313

138

624

Mn

7.0

4.5

1.4

1.00

16.2

5.80

1.33

15.0

Na

7511

2133

643

3913

12239

7228

4420

11539

M – arithmetic mean, SD – standard deviation, SEM – standard error of mean, Min – minimum value, Max – maximum value, P 0.025 – percentile with 0.025 level, P 0.975 – percentile with 0.975 level.

 

The ratios of means and the reliability of difference between mean values of Br, Ca, K, Mg, Mn, and Na mass fraction in normal, benign hypertrophic and cancerous prostate are presented in Table 3.

Table 3. Comparison of mean values (M ± SEM) of Br, Ca, K, Mg, Mn, and Na mass fractions (mg/kg, dry mass basis) in normal, benign hyperplastic (BPH), and cancerous (PCa) prostate

Element

Prostatic tissue

Ratios, p (Student’s t-test)

Normal

41-79 year

n=37

BPH

56-78 year

n=27

Cancer

51-78 year

n=23

BPH

 to

Normal

Cancer

 to

Normal

Cancer

 to

BPH

Br

32.9 ± 3.6

30.4 ± 3.6

115 ± 10

0.92

3.50b

3.78b

Ca

2280 ± 178

2032 ± 165

674 ± 58

0.89

0.30b

0.33b

K

11211 ± 414

14472 ± 740

8542 ± 504

1.29b

0.76b

0.59b

Mg

1118 ± 76

1201 ± 83

346 ± 61

1.07

0.31b

0.29b

Mn

1.24 ± 0.07

1.19 ± 0.09

7.0 ± 1.4

0.96

5.65a

5.88a

Na

11100 ± 408

11612 ± 869

7511 ± 643

1.05

0.68b

0.65a

M arithmetic mean, SEM standard error of mean,

Statistically significant difference: ap<0.01, bp<0.001.

 

The comparison of our results with published data for Br, Ca, K, Mg, Mn, and Na mass fraction in normal, benign hypertrophic and cancerous prostate is shown in Table 4.

Table 4 Median, minimum and maximum value of means of chemical element contents (mg/kg, dry mass basis) in normal, benign hyperplastic (BPH), and cancerous (PCa) prostate according to data from the literature in comparison with our results

Prostate

tissue

(year)

Element

Published data [Reference]

This work

results

Median

of means

(n)*

Minimum

of means

M or M ± SD, (n)**

Maximum

of means

M or M ± SD, (n)**

M ± SD

 

 

Normal

Br

14 (3)

12 ± 8 (4) [32]

21 (12) [33]

32.9 ± 17.7

Ca

1870(14)

430 ± 120 (21) [34]

7500 ± 12300 (57) [35]

2280 ± 874

K

9900(12)

3840 (8) [36]

12200 ± 1500 (8) [37]

11211 ± 2071

Mg

900(12)

498 ± 172 (13) [35]

2056 ± 476 (21) [38]

1118 ± 396

Mn

6.0 (11)

<0.47 (12) [33]

106 ± 18 (5) [39]

1.24 ± 0.32

Na

6100(7)

23 ± 26 (13) [35]

13700 ± 3500 (4) [40]

11100 ± 2159

BPH

Br

19.8 (2)

18.0 ± 9.5 (27) [41]

21.5 ± 13.0 (9) [42]

30.4 ± 18.4

Ca

2100 (7)

600 ± 120 (2) [43]

5100 ± 3200(9) [42]

2032 ± 547

K

7400 (6)

1010 ± 95 (27) [41]

12800 ± 1900 (43) [37]

14472 ± 2454

Mg

820 (6)

566 ± 130 (25) [44]

1560 ± 50 (10) [45]

1201 ± 276

Mn

10.8 (4)

6.5 (-) [43]

23 ± 13 (27) [41]

1.19 ± 0.31

Na

7800 (1)

7800 (34) [46]

7800 (34) [46]

11612 ± 2882

PCa

Br

1.5 (1)

1.5 ± 6.0 (27) [41]

1.5 ± 6.0 (27) [41]

115 ± 45

Ca

2940 (7)

1100 (4) [46]

410000 ± 43000 (1) [43]

674 ± 193

K

3620 (4)

740 ± 90 (27) [41]

5600 (4) [46]

8542 ± 1672

Mg

935 (5)

361 ± 174 (25) [44]

1050 ± 720 (11) [47]

346 ± 193

Mn

8.0 (4)

2.74 ± 0.27 (1) [43]

160 ± 22 (1) [39]

7.0 ± 4.5

Na

5100 (1)

5100 (4) [46]

5100 (4) [46]

7511 ± 2133

M arithmetic mean, SD standard deviation, (n)* number of all references, (n)** number of samples

Table 5 contains parameters of the importance (sensitivity, specificity and accuracy) of Br, Ca, Mg, and Mn mass fraction for the diagnosis of PCa calculated in this work.

 

Table 5. Parameters of the importance (sensitivity, specificity and accuracy) of some chemical element mass fractions for the diagnosis of PCa (an estimation is made for “PCa or intact and BPH tissue”)

Element

 

 

Limit for PCa (M ± SD)

mg/kg, dry mass basis

 

Sensitivity

%

 

 

Specificity

%

Accuracy

%

Br

 

70 mg/kg - Lower limit (M-SD)

 

91 ± 6

 

97 ± 2

95 ± 2

Ca

 

1060 mg/kg - Upper limit (M+2SD)

 

100-9

 

100-2

100-2

Mg

 

730 mg/kg - Upper limit (M+2SD)

 

100-9

 

92 ± 4

93 ± 3

Mn

 

2.2 mg/kg - Lower limit (~M-SD)

 

91 ± 9

 

100-2

98 ± 2

M - arithmetic mean, SD – standard deviation.

Figure 1 depicts individual data sets for Br, Ca, K, Mg, Mn, and Na mass fraction in all samples of normal, benign hypertrophic and cancerous prostate.

Figure 1. Individual data sets for Br, Ca, K, Mg, Mn, and Na mass fractions in samples of normal (1), benign hypertrophic (2) and cancerous prostate (3).

Discussion

As was shown by us [15,21,28]  the use of CRM IAEA H-4 as a certified reference material for the analysis of samples of prostate tissue can be seen as quite acceptable. Good agreement of the Br, Ca, K, Mg, Mn, and Na contents analyzed by INAA-SLR with the certified data of CRM IAEA H-4 (Table 1) indicates an acceptable accuracy of the results obtained in the study of chemical elements of the prostate presented in Tables 2–4.

The mean values and all selected statistical parameters were calculated for six (Br, Ca, K, Mg, Mn, and Na) chemical element mass fractions (Table 2). The mass fraction of these chemical elements were measured in all, or a major portion of normal prostate samples. The masses of BPH and PCa samples varied very strong from a few milligrams (sample from needle biopsy material) to 100 mg (sample from resected material). Therefore, in BPH and PCa prostates mass fractions of Br were measured in all samples, while mass fractions of Ca, K, Mg, Mn, and Na were determined in 22 samples (11 and 11 samples, respectively).

From Table 3, it is observed that in benign hypertrophic tissues the mass fractions of Br, Ca, Mg, Mn, and Na not differ from normal levels while the mass fraction of K is significantly (p=0.0014) higher. In cancerous tissue the mass fractions of Ca (p=0.000000003), K (p=0.004), Mg p=0.000000005), and Na (p=0.0002) are significantly lower, and mass fractions of Br (p=0.000000007) and Mn (p=0.0017) are significantly higher than in normal tissues of the prostate. All these elements show similar variations in cancerous tissues when compared with benign hypertrophic tissues of the prostate. The mass fractions of Ca (p=0.000004), K (p=0.0000035), Mg p=0.00000015), and Na (p=0.0013) are significantly lower, and mass fractions of Br (p=0.000000004) and Mn (p=0.0016) are significantly higher than in benign hypertrophic tissues.

The results for all chemical element contents in the prostates of the control group (mean age 55 ± 11 years, range 41-79) are in accordance with our earlier findings in prostates of apparently healthy men aged 41-60 [15]. Values obtained for Br, Ca, K, Mg, Mn, and Na contents (Table 4) agree well with median of mean values cited by other researches for the human prostate [32-47]. Data of the literature also includes samples obtained from patients who died from different diseases.  A number of values for chemical element mass fractions were not expressed on a dry mass basis in the cited literature. Therefore, we calculated these values using published data for water - 80% [45] and ash - 1% on wet mass basis [65] contents in the prostate of adult men. Our results for for Br, Ca, K, Mg, Mn, and Na are in accordance with the medians of earlier findings in benign hypertrophic tissues of prostate (Table 4). In cancerous prostate tissues our results were comparable with published data for Mg, Mn, and Na contents, some lover for Ca, some higher for K, and almost two orders of magnitude higher for Br (Table 4).

Analysis of chemical element mass fraction in prostate tissue could become a powerful diagnostic tool. To a large extent, the resumption of the search for new methods for early diagnosis of PCa was due to experience gained in a critical assessment of the limited capacity of the prostate specific antigen (PSA) serum test [66]. In addition to the PSA serum test and morphological study of needle-biopsy cores of the prostate, the development of other highly precise testing methods seems to be very useful. Experimental conditions of the present study were approximated to the hospital conditions as closely as possible. In BPH and PCa cases we analyzed a part of the material obtained from a puncture transrectal biopsy of the indurated site in the prostate. Therefore, our data allow us to evaluate adequately the importance of chemical element mass fraction for the diagnosis of PCa. As is evident from individual data sets (Figure 1), the Br, Ca, Mg, and Mn mass fraction are the most informative for a differential diagnosis. For example, if 1060 mg/kg (M±2SD) is the value of Ca mass fraction assumed to be the upper limit for PCa (Figure 1) and an estimation is made for “PCa or intact and BPH tissue”, the following values are obtained:

Sensitivity = {True Positives (TP)/[TP + False Negatives (FN)]} ·100% = 100-9%;

Specificity = {True Negatives (TN)/[TN + False Positives (FP)]} ·100% = 100-2%;

Accuracy =  [(TP+TN)/(TP+FP+TN+FN)] ·100% = 100-2%.

The number of people (samples) examined was taken into account for calculation of confidence intervals [67].  In other words, if Ca mass fraction in a prostate biopsy sample does not exceed 1060 mg/kg, one could diagnose a malignant tumor with an accuracy 100-2%. Thus, using the Ca mass fraction-test makes it possible to diagnose cancer in 100-2%; cases (sensitivity). The same way parameters of the importance (sensitivity, specificity and accuracy) of Br, Mg, and Mn mass fraction for the diagnosis of PCa were calculated (Table 5).

It should be noted, however, that Br is a component of many tranquilizers. It is possible that the increase in Br content could be explained by uncontrolled use of tranquilizers in the group of PCa patients. Therefore, for diagnostic purposes, data for Br content should be used with caution.

Conclusion

In this work, elemental analysis was carried out in the tissue samples of normal, benign hypertrophic, and carcinomatous prostates using INAA-SLR. It was shown that INAA-SLR is an adequate analytical tool for the non-destructive determination of Br, Ca, K, Mg, Mn, and Na content in the tissue samples of human prostate, including needle-biopsy cores. It was observed that in benign hypertrophic tissues the contents of Br, Ca, K, Mg, Mn, and Na were equal to those in normal prostate tissues with the exception of higher K level. The contents of Ca, K, Mg, and Na were significantly lower and those of Br and Mn were significantly higher in cancerous tissues than in normal and BPH tissues. Finally, we propose to use the Ca, Mg, and Mn mass fraction in a needle-biopsy core as an accurate tool to diagnose prostate cancer. Further studies on larger number of samples are required to confirm our findings, to study the impact of the trace elements on prostate cancer etiology and to examine the long-term pathological outcome.

Acknowledgements

We are grateful to Dr. Tatyana Sviridova, Medical Radiological Research Center, Obninsk, and to the late Prof. A.A. Zhavoronkov, Institute of Human Morphology, Russian Academy of Medical Sciences, Moscow, for supplying prostate samples.

Competing interests

All other authors declare no competing interests.

Authors’ contributions

VZ was responsible for the study design, INAA-LLR analyses, and manuscript preparation. SZ was responsible for data collection, data entry, statistical analyses and assistance with manuscript preparation. Both authors read and approved of the final manuscript.

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Editorial Information

Editor-in-Chief

Ivan Gout
University College London

Article Type

Research Article

Publication history

Received date: July 28, 2016
Accepted date: August 08, 2016
Published date: August 10, 2016

Copyright

©2016 Zaichick V. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Zaichick V, Zaichick S (2016) Distinguishing malignant from benign prostate using Br, Ca, K, Mg, Mn, and Na content in prostatic tissue. Integr Mol Med 3: DOI: 10.15761/IMM.1000234.

Corresponding author

Vladimir Zaichick

Professor, Radionuclide Diagnostics Department, Medical Radiological Research Centre Koroleva Str.- 4, Obninsk 249036 Kaluga Region, Russia, Tel: +7 (48439) 60289, Fax: +7 (495) 956 1440

E-mail : vezai@obninsk.com

Table 1. NAA-SLR data of chemical element contents in reference material IAEA H-4 (animal muscle) compared to certified values (mg/kg, dry mass basis)

Element

 

IAEA H-4 (animal muscle)

 

This work results

 

95% confidence interval

 

Mean ± SD

Br

 

3.5 – 4.7a

 

5.0 ± 0.9

Ca

 

163 – 213a

 

238 ± 59

K

 

15300 – 16400a

 

16200 ± 3800

Mg

 

990 – 1110a

 

1100 ± 190

Mn

 

0.48 – 0.55b

 

0.55 ± 0.11

Na

 

1930 – 2180a

 

2190 ± 140

Mean – arithmetical mean, SD – standard deviation, a- certified values, b – non-certified values.

Table 2. Some statistical parameters of Br, Ca, K, Mg, Mn, and Na mass fractions (mg/kg, dry mass basis) in normal, benign hyperplastic (BPH), and cancerous (PCa) prostate

Tissue

Parameter

Mean

SD

SEM

Min

Max

Median

P 0.025

P 0.975

Normal

Br

32.9

17.7

3.6

12.5

80.7

28.2

12.6

70.9

n=37

Ca

2280

874

178

1205

4908

2082

1340

4386

K

11211

2071

414

7100

14328

11399

7100

13998

Mg

1118

396

76

604

2060

1062

626

1963

Mn

1.24

0.32

0.07

0.40

1.80

1.30

0.65

1.75

Na

11100

2159

408

6834

15300

11071

6879

15161

BPH

Br

30.4

18.4

3.6

5.5

77

25.6

5.75

66.7

n=27

Ca

2032

547

165

1168

2762

1898

1173

2757

K

14472

2454

740

11683

20519

13552

12025

19744

Mg

1201

276

83

687

1585

1263

749

1552

Mn

1.19

0.31

0.09

0.80

1.80

1.20

0.80

1.73

Na

11612

2882

869

7762

15503

10564

7893

15400

PCa

Br

115

45

9.5

11.3

193

115

13.1

184

n=23

Ca

674

193

58

382

952

751

411

931

K

8542

1672

504

6047

11833

8784

6270

11402

Mg

346

193

61

136

632

313

138

624

Mn

7.0

4.5

1.4

1.00

16.2

5.80

1.33

15.0

Na

7511

2133

643

3913

12239

7228

4420

11539

M – arithmetic mean, SD – standard deviation, SEM – standard error of mean, Min – minimum value, Max – maximum value, P 0.025 – percentile with 0.025 level, P 0.975 – percentile with 0.975 level.

 

Table 3. Comparison of mean values (M ± SEM) of Br, Ca, K, Mg, Mn, and Na mass fractions (mg/kg, dry mass basis) in normal, benign hyperplastic (BPH), and cancerous (PCa) prostate

Element

Prostatic tissue

Ratios, p (Student’s t-test)

Normal

41-79 year

n=37

BPH

56-78 year

n=27

Cancer

51-78 year

n=23

BPH

 to

Normal

Cancer

 to

Normal

Cancer

 to

BPH

Br

32.9 ± 3.6

30.4 ± 3.6

115 ± 10

0.92

3.50b

3.78b

Ca

2280 ± 178

2032 ± 165

674 ± 58

0.89

0.30b

0.33b

K

11211 ± 414

14472 ± 740

8542 ± 504

1.29b

0.76b

0.59b

Mg

1118 ± 76

1201 ± 83

346 ± 61

1.07

0.31b

0.29b

Mn

1.24 ± 0.07

1.19 ± 0.09

7.0 ± 1.4

0.96

5.65a

5.88a

Na

11100 ± 408

11612 ± 869

7511 ± 643

1.05

0.68b

0.65a

M arithmetic mean, SEM standard error of mean,

Statistically significant difference: ap<0.01, bp<0.001.

 

Table 4 Median, minimum and maximum value of means of chemical element contents (mg/kg, dry mass basis) in normal, benign hyperplastic (BPH), and cancerous (PCa) prostate according to data from the literature in comparison with our results

Prostate

tissue

(year)

Element

Published data [Reference]

This work

results

Median

of means

(n)*

Minimum

of means

M or M ± SD, (n)**

Maximum

of means

M or M ± SD, (n)**

M ± SD

 

 

Normal

Br

14 (3)

12 ± 8 (4) [32]

21 (12) [33]

32.9 ± 17.7

Ca

1870(14)

430 ± 120 (21) [34]

7500 ± 12300 (57) [35]

2280 ± 874

K

9900(12)

3840 (8) [36]

12200 ± 1500 (8) [37]

11211 ± 2071

Mg

900(12)

498 ± 172 (13) [35]

2056 ± 476 (21) [38]

1118 ± 396

Mn

6.0 (11)

<0.47 (12) [33]

106 ± 18 (5) [39]

1.24 ± 0.32

Na

6100(7)

23 ± 26 (13) [35]

13700 ± 3500 (4) [40]

11100 ± 2159

BPH

Br

19.8 (2)

18.0 ± 9.5 (27) [41]

21.5 ± 13.0 (9) [42]

30.4 ± 18.4

Ca

2100 (7)

600 ± 120 (2) [43]

5100 ± 3200(9) [42]

2032 ± 547

K

7400 (6)

1010 ± 95 (27) [41]

12800 ± 1900 (43) [37]

14472 ± 2454

Mg

820 (6)

566 ± 130 (25) [44]

1560 ± 50 (10) [45]

1201 ± 276

Mn

10.8 (4)

6.5 (-) [43]

23 ± 13 (27) [41]

1.19 ± 0.31

Na

7800 (1)

7800 (34) [46]

7800 (34) [46]

11612 ± 2882

PCa

Br

1.5 (1)

1.5 ± 6.0 (27) [41]

1.5 ± 6.0 (27) [41]

115 ± 45

Ca

2940 (7)

1100 (4) [46]

410000 ± 43000 (1) [43]

674 ± 193

K

3620 (4)

740 ± 90 (27) [41]

5600 (4) [46]

8542 ± 1672

Mg

935 (5)

361 ± 174 (25) [44]

1050 ± 720 (11) [47]

346 ± 193

Mn

8.0 (4)

2.74 ± 0.27 (1) [43]

160 ± 22 (1) [39]

7.0 ± 4.5

Na

5100 (1)

5100 (4) [46]

5100 (4) [46]

7511 ± 2133

M arithmetic mean, SD standard deviation, (n)* number of all references, (n)** number of samples

 

Table 5. Parameters of the importance (sensitivity, specificity and accuracy) of some chemical element mass fractions for the diagnosis of PCa (an estimation is made for “PCa or intact and BPH tissue”)

Element

 

 

Limit for PCa (M ± SD)

mg/kg, dry mass basis

 

Sensitivity

%

 

 

Specificity

%

Accuracy

%

Br

 

70 mg/kg - Lower limit (M-SD)

 

91 ± 6

 

97 ± 2

95 ± 2

Ca

 

1060 mg/kg - Upper limit (M+2SD)

 

100-9

 

100-2

100-2

Mg

 

730 mg/kg - Upper limit (M+2SD)

 

100-9

 

92 ± 4

93 ± 3

Mn

 

2.2 mg/kg - Lower limit (~M-SD)

 

91 ± 9

 

100-2

98 ± 2

M - arithmetic mean, SD – standard deviation.

Figure 1. Individual data sets for Br, Ca, K, Mg, Mn, and Na mass fractions in samples of normal (1), benign hypertrophic (2) and cancerous prostate (3).