Thyroid malignant nodules (TMNs) are the most common endocrine cancer and the fifth most frequently occurring type of malignancies
Besides iodine, many other ChEs have also essential physiological functions
In our previous studies the complex of in vivo and in vitro nuclear analytical and related methods was developed and used for the investigation of iodine and other ChEs contents in the normal and pathological thyroid
To date, the etiology and pathogenesis of TMNs must be considered as multifactorial. The present study was performed to find out differences in ChEs contents between the group of cancerous tissues and tissue adjacent to tumor, as well as to clarify the role of some ChEs in the etiology of TMNs. Having this in mind, the aim of this exploratory study was to examine differences in the content of silver (Ag), calcium (Ca), chlorine (Cl), cobalt (Co), chromium (Cr), cooper (Cu), iron (Fe), mercury (Hg), iodine (I), potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), rubidium (Rb), ammonium (Sb), scandium (Sc), selenium (Se), strontium (Sr), and zinc (Zn) in nodular and adjacent to nodules tissues of thyroids with TMNs using a non-destructive energy-dispersive X-Ray fluorescent analysis (EDXRF) combined with instrumental neutron activation analysis with high resolution spectrometry of short- and long-lived radionuclides (INAA-SLR and INAA-LLR, respectively), and to compare the levels of these ChEs in two groups (nodular and adjacent to nodules tissues) of the cohort of TMNs samples. Moreover, for understanding a possible role of ChEs in etiology and pathogenesis of TMNs results of the study were compared with previously obtained data for the same ChEs in “normal” thyroid tissue
All patients with TMNs (n=41, mean age M±SD was 46±15 years, range 16-75) were hospitalized in the Head and Neck Department of the Medical Radiological Research Centre (MRRC), Obninsk.. Thick-needle puncture biopsy of suspicious nodules of the thyroid was performed for every patient, to permit morphological study of thyroid tissue at these sites and to estimate their trace element contents. In all cases the diagnosis has been confirmed by clinical and morphological results obtained during studies of biopsy and resected materials. Histological conclusions for malignant tumors were: 25 papillary adenocarcinomas, 8 follicular adenocarcinomas, 7 solid carcinomas, and 1 reticulosarcoma. Tissue samples of tumor and visually intact tissue adjacent to tumor were taken from resected materials.
“Normal” thyroids for the control group samples were removed at necropsy from 105 deceased (mean age 44±21 years, range 2-87), who had died suddenly. The majority of deaths were due to trauma. A histological examination in the control group was used to control the age norm conformity, as well as to confirm the absence of micro-nodules and latent cancer.
All studies were approved by the Ethical Committees of MRRC. All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments, or with comparable ethical standards. Informed consent was obtained from all individual participants included in the study
All tissue samples obtained from tumors and visually intact tissue adjacent to tumors were divided into two portions using a titanium scalpel to prevent contamination by ChEs of stainless steel
The content of Cu, Fe, Rb, Sr, and Zn were determined by EDXRF. Details of the relevant facility for this method, source with 109Cd radionuclide, methods of analysis and the results of quality control were presented in our earlier publications concerning the EDXRF of ChE contents in human thyroid
The content of Br, Ca, Cl, I, K, Mg, Mn, and Na were determined by INAA-SLR using a horizontal channel equipped with the pneumatic rabbit system of the WWR-c research nuclear reactor (Branch of Karpov Institute, Obninsk). Details of used neutron flux, nuclear reactions, radionuclides, gamma-energies, spectrometric unit, sample preparation and measurement were presented in our earlier publications concerning the INAA-SLR of ChE contents in human thyroid
In a few days after non-destructive INAA-SLR all thyroid samples were repacked and used for INAA-LLR. A vertical channel of the WWR-c research nuclear reactor (Branch of Karpov Institute, Obninsk).was applied to determine the content of Ag, Co, Cr, Fe, Hg, Rb, Sb, Sc, Se, and Zn by INAA-LLR. Details of used neutron flux, nuclear reactions, radionuclides, gamma-energies, spectrometric unit, sample preparation and measurement were presented in our earlier publications concerning the INAA-LLR of ChE contents in human thyroid
A dedicated computer program for INAA-SLR and INAA-LLR mode optimization was used
resents 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 Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg,Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn mass fraction in “tumor” and “adjacent” groups of thyroid tissue samples.
The ratios of means and the comparison of mean values of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn mass fractions in pairs of sample groups such as “normal” and “tumor”, “normal” and “adjacent”, and also “adjacent” and “tumor” are presented in Table 2, 3, and 4, respectively.
As was shown before
From Table 2, it is observed that in malignant tissue the mass fraction of Ag, Cl, Co, Cr, Cu, Hg, K, Mg, Na, and Rb are approximately 13, 2.3, 1.4, 1.6, 3.4, 20, 1.6, 1.6, 1.3, and 1.5 times, respectively, higher whereas mass fraction of I is 26 times lower than in the normal thyroid. Thus, if we accept the ChEs contents in thyroid glands of the “normal” group as a norm, we have to conclude that with a malignant transformation the Ag, Cl, Co, Cr, Cu, Hg, K, Mg, Na, and Rb contents in thyroid tissue significantly changed. In a general sense Cr, Cu, Fe, K, Mg, Mn, Na, Sc, and Zn contents found in the “normal” and “adjacent” groups of thyroid tissue samples were very similar (Table 3). However, in the “adjacent” group mean mass fractions of Ag, Cl, Co, Hg, I, Rb, and Se were approximately 33, 1.6, 1.8, 52, 1.7, 2.3, and 1.3 times, respectively, higher, while mean values of Ca and Sr content were 2 and 4 times lower than in the “normal” group.
Tissue |
Element |
Mean |
SD |
SEM |
Min |
Max |
Median |
P 0.025 |
P 0.975 |
Cancer |
Ag |
0.193 |
0.215 |
0.041 |
0.0075 |
1.02 |
0.147 |
0.0080 |
0.705 |
(tumor) |
Ca |
2397 |
2368 |
558 |
452 |
8309 |
1302 |
467 |
7428 |
|
Cl |
7699 |
2900 |
703 |
4214 |
14761 |
7216 |
4240 |
13619 |
|
Co |
0.0550 |
0.0309 |
0.0060 |
0.0042 |
0.143 |
0.0497 |
0.0159 |
0.129 |
|
Cr |
0.835 |
0.859 |
0.157 |
0.0390 |
3.50 |
0.460 |
0.0941 |
3.05 |
|
Cu |
14.5 |
9.4 |
2.6 |
4.00 |
32.6 |
10.9 |
4.21 |
31.4 |
|
Fe |
243 |
177 |
29 |
55.1 |
887 |
200 |
58.2 |
679 |
|
Hg |
0.824 |
0.844 |
0.149 |
0.0685 |
3.75 |
0.475 |
0.0689 |
2.85 |
|
I |
71.8 |
62.0 |
10 |
2.00 |
261 |
62.1 |
2.93 |
192 |
|
K |
9655 |
4444 |
970 |
1660 |
19225 |
8746 |
3381 |
19035 |
|
Mg |
450 |
232 |
51 |
122 |
1033 |
408 |
126 |
931 |
|
Mn |
1.90 |
1.41 |
0.32 |
0.100 |
5.79 |
1.59 |
0.100 |
5.37 |
|
Na |
8556 |
2959 |
646 |
4083 |
17284 |
7264 |
4704 |
14543 |
|
Rb |
12.6 |
4.6 |
0.7 |
5.50 |
27.4 |
11.2 |
5.84 |
19.8 |
|
Sb |
0.124 |
0.081 |
0.015 |
0.0160 |
0.381 |
0.108 |
0.0174 |
0.315 |
|
Sc |
0.0077 |
0.0129 |
0.0020 |
0.0002 |
0.0565 |
0.0023 |
0.0002 |
0.0447 |
|
Se |
2.04 |
1.02 |
0.18 |
0.143 |
4.70 |
1.80 |
0.663 |
4.33 |
|
Sr |
6.25 |
7.83 |
1.63 |
0.930 |
30.8 |
3.00 |
0.985 |
25.0 |
|
Zn |
89.7 |
57.6 |
10.8 |
36.7 |
326 |
67.7 |
37.7 |
324 |
Cancer |
Ag |
0.503 |
0.450 |
0.103 |
0.079 |
2.00 |
0.303 |
0.0984 |
1.53 |
(adjacent |
Ca |
862 |
560 |
140 |
81.0 |
1909 |
672 |
149 |
1822 |
thyroid |
Cl |
5339 |
22512 |
581 |
2526 |
11767 |
4922 |
2595 |
10201 |
tissue) |
Co |
0.0707 |
0.0581 |
0.0120 |
0.0152 |
0.205 |
0.0455 |
0.0170 |
0.201 |
|
Cr |
0.556 |
0.468 |
0.094 |
0.0512 |
1.58 |
0.457 |
0.0589 |
1.56 |
|
Cu |
8.08 |
3.15 |
1.58 |
4.90 |
12.1 |
7.65 |
5.01 |
11.9 |
|
Fe |
244 |
137 |
27 |
95.2 |
752 |
213 |
104 |
591 |
|
Hg |
2.19 |
1.92 |
0.38 |
0.0160 |
7.78 |
1.43 |
0.158 |
6.50 |
|
I |
3183 |
1673 |
301 |
563 |
8240 |
2982 |
853 |
7766 |
|
K |
5717 |
2525 |
652 |
2097 |
12681 |
5429 |
2466 |
10953 |
|
Mg |
339 |
407 |
105 |
15.0 |
1412 |
199 |
15.0 |
1287 |
|
Mn |
1.72 |
1.63 |
0.41 |
0.410 |
6.78 |
1.15 |
0.429 |
5.54 |
|
Na |
7671 |
2597 |
649 |
3865 |
14373 |
7434 |
4169 |
13009 |
|
Rb |
18.8 |
17.0 |
3.3 |
5.00 |
67.0 |
11.9 |
5.69 |
65.6 |
|
Sb |
0.247 |
0.416 |
0.085 |
0.0069 |
1.77 |
0.0634 |
0.0159 |
1.38 |
|
Sc |
0.0059 |
0.0134 |
0.0030 |
0.0002 |
0.0539 |
0.0002 |
0.0002 |
0.0442 |
|
Se |
3.08 |
1.67 |
0.33 |
0.704 |
6.91 |
2.56 |
0.942 |
6.89 |
|
Sr |
1.16 |
0.29 |
0.14 |
0.83 |
1.40 |
1.20 |
0.84 |
1.40 |
|
Zn |
109 |
55 |
11 |
20.4 |
272 |
109 |
29.1 |
213 |
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.
Significant changes were found in tumor ChEs composition in comparison with thyroid tissue adjacent to tumor. In malignant tumor Ca, Cl, Cu, K, and Sr contents were approximately 2.8, 1.4, 1.8, 1.7, and 5.4 times, respectively, higher, while Ag, Hg, I, and Se content 2.6, 2.6, 43, and 1.5 times, respectively, lower than in “adjacent” group of tissue samples (Table 4).
Element |
Thyroid tissue |
Ratio |
|||
Normal thyroid |
Cancer (tumor) |
Student’s t-test p |
U-test p |
Tumor/Normal |
|
Ag |
0.0151±0.0016 |
0.193±0.041 |
|
|
12.8 |
Ca |
1711±109 |
2397±558 |
0.243 |
>0.05 |
1.40 |
Cl |
3400±174 |
7699±703 |
|
|
2.26 |
Co |
0.0399±0.0030 |
0.0550±0.0060 |
|
|
1.38 |
Cr |
0.539±0.032 |
0.835±0.157 |
0.073 |
|
1.55 |
Cu |
4.23±0.18 |
14.5±2.6 |
|
|
3.43 |
Fe |
223±10 |
243±29 |
0.519 |
>0.05 |
1.09 |
Hg |
0.0421±0.0041 |
0.824±0.149 |
|
|
19.6 |
I |
1841±107 |
71.8±10.0 |
|
|
0.039 |
K |
6071±306 |
9655±970 |
|
|
1.59 |
Mg |
285±17 |
450±51 |
|
|
1.58 |
Mn |
1.35±0.07 |
1.90±0.32 |
0.107 |
>0.05 |
1.41 |
Na |
6702±178 |
8556±646 |
|
|
1.28 |
Rb |
8.16±0.49 |
12.6±0.7 |
|
|
1.54 |
Sb |
0.111±0.008 |
0.124±0.015 |
0.423 |
>0.05 |
1.12 |
Sc |
0.0046±0.0008 |
0.0077±0.0020 |
0.223 |
>0.05 |
1.67 |
Se |
2.32±0.14 |
2.04±0.18 |
0.235 |
>0.05 |
0.88 |
Sr |
4.55±0.37 |
6.25±1.63 |
0.319 |
>0.05 |
1.37 |
Zn |
105.1±4.3 |
89.7±10.8 |
0.191 |
>0.05 |
0.85 |
M – arithmetic mean, SEM – standard error of mean, Statistically significant values are in
Characteristically, elevated or reduced levels of ChEs observed in thyroid nodules are discussed in terms of their potential role in the initiation and promotion of these thyroid lesions. In other words, using the low or high levels of the ChEs in affected thyroid tissues researchers try to determine the role of the deficiency or excess of each ChE in the etiology and pathogenesis of thyroid diseases. In our opinion, abnormal levels of many ChEs in TMNs could be and cause, and also effect of thyroid tissue transformation. From the results of such kind studies, it is not always possible to decide whether the measured decrease or increase in ChEs level in pathologically altered tissue is the reason for alterations or vice versa. According to our opinion, investigation of ChEs contents in thyroid tissue adjacent to malignant nodules and comparison obtained results with ChEs levels typical of “normal” thyroid gland may give additional useful information on the topic because these data show conditions of tissue in which TMNs were originated and developed.
Thus, from results obtained, it was possible to conclude that the common characteristics of TMNs in comparison with “normal” thyroid and visually “intact” thyroid tissue adjacent to malignant tumors were elevated levels of Cl and K, as well as drastically reduced level of I. (Tables 2 and 4) . The last finding meant that thyroid tissue adjacent to malignant nodules kept the main function of thyroid gland, while malignantly transformed thyroid cells lost its capacity to accumulate I. Furthermore, the ChEs composition of thyroid tissue adjacent to tumor did not equal ChEs contents of “normal” thyroid (Table 3). Moreover, contents of such elements as Ag, Hg, I, and Se in adjacent tissue were higher than in tumor (Table 4). From here, the excessive accumulation of Ag, Hg, I, and Se by thyroid tissue is likely to precede the TMNs origination and development.
Element |
Thyroid tissue |
Ratio |
|||
Normal thyroid |
Cancer (adjacent) |
Student’s t-test p� |
U-test p |
Adjacent/Normal |
|
Ag |
0.0151±0.0016 |
0.503±0.103 |
|
|
33.3 |
Ca |
1711±109 |
862±140 |
|
|
0.50 |
Cl |
3400±174 |
5339±581 |
|
|
1.57 |
Co |
0.0399±0.0030 |
0.0707±0.0120 |
|
|
1.77 |
Cr |
0.539±0.032 |
0.556±0.094 |
0.860 |
>0.05 |
1.03 |
Cu |
4.23±0.18 |
8.08±1.58 |
0.092 |
>0.05 |
1.91 |
Fe |
223±10 |
244±27 |
0.473 |
>0.05 |
1.09 |
Hg |
0.0421±0.0041 |
2.19±0.38 |
|
|
52.0 |
I |
1841±107 |
3183±301 |
|
|
1.73 |
K |
6071±306 |
5717±652 |
0.629 |
>0.05 |
0.94 |
Mg |
285±17 |
339±105 |
0.617 |
>0.05 |
1.19 |
Mn |
1.35±0.07 |
1.72±0.41 |
0.391 |
>0.05 |
1.27 |
Na |
6702±178 |
7671±649 |
0.168 |
>0.05 |
1.14 |
Rb |
8.16±0.49 |
18.8±3.3 |
|
|
2.30 |
Sb |
0.111±0.008 |
0.247±0.085 |
0.122 |
>0.05 |
2.23 |
Sc |
0.0046±0.0008 |
0.0059±0.0030 |
0.628 |
>0.05 |
1.28 |
Se |
2.32±0.14 |
3.08±0.33 |
|
|
1.33 |
Sr |
4.55±0.37 |
1.16±0.14 |
|
|
0.25 |
Zn |
105.1±4.3 |
109±11 |
0.731 |
>0.05 |
1.04 |
M – arithmetic mean, SEM – standard error of mean, Statistically significant values are in
Ag is a TE with no recognized trace metal value in the human body
Cl and Na are ubiquitous, extracellular electrolytes essential to more than one metabolic pathway. In the body, Cl and Na mostly present as sodium chloride. Therefore, as usual, there is a correlation between Na and Cl contents in tissues and fluids of human body. Because Cl is halogen like I, in the thyroid gland the biological behavior of chloride has to be similar to the biological behavior of iodide. The main source of natural Cl for human body is salt in food and chlorinated drinking water. Environment (air, water and food) polluted by artificial nonorganic Cl-contained compounds, for example such as sodium chlorate (NaClO3), and organic Cl-contained compounds, for example such as polychlorinated biphenyls (PCBs) and dioxin, is other source. There is a clear association between using chlorinated drinking water, levels NaClO3, PCBs and dioxin in environment and thyroid disorders, including cancer
Element |
Thyroid tissue |
Ratio |
|||
Cancer (adjacent) |
Cancer (tumor) |
Student’s t-test p� |
U-test p |
Adjacent/Tumor |
|
Ag |
0.503±0.103 |
0.193±0.041 |
|
|
0.38 |
Ca |
862±140 |
2397±558 |
|
|
2.78 |
Cl |
5339±581 |
7699±703 |
|
|
1.44 |
Co |
0.0707±0.0120 |
0.0550±0.0060 |
0.232 |
>0.05 |
0.78 |
Cr |
0.556±0.094 |
0.835±0.157 |
0.133 |
>0.05 |
1.50 |
Cu |
8.08±1.58 |
14.5±2.6 |
0.051 |
|
1.79 |
Fe |
244±27 |
243±29 |
0.983 |
>0.05 |
1.00 |
Hg |
2.19±0.38 |
0.824±0.149 |
|
|
0.38 |
I |
3183±301 |
71.8±10.0 |
|
|
0.023 |
K |
5717±652 |
9655±970 |
|
|
1.69 |
Mg |
339±105 |
450±51 |
0.351 |
>0.05 |
1.33 |
Mn |
1.72±0.41 |
1.90±0.32 |
0.729 |
>0.05 |
1.10 |
Na |
7671±649 |
8556±646 |
0.340 |
>0.05 |
1.12 |
Rb |
18.8±3.3 |
12.6±0.7 |
0.082 |
>0.05 |
0.67 |
Sb |
0.247±0.085 |
0.124±0.015 |
0.166 |
>0.05 |
0.50 |
Sc |
0.0059±0.0030 |
0.0077±0.0020 |
0.624 |
>0.05 |
1.31 |
Se |
3.08±0.33 |
2.04±0.18 |
|
|
0.66 |
Sr |
1.16±0.14 |
6.25±1.63 |
|
|
5.39 |
Zn |
109±11 |
89.7±10.8 |
0.206 |
>0.05 |
0.82 |
M – arithmetic mean, SEM – standard error of mean, Statistically significant values are in
Health effects of high Co occupational, environmental, dietary and medical exposure are characterized by a complex clinical syndrome, mainly including neurological, cardiovascular and endocrine deficits, including hypothyroidism
The general population can be exposed to low levels of Cr primarily through consumption of food and to a lesser degree through inhalation of ambient air and ingestion of drinking water
Cu is a ubiquitous element in the human body which plays many roles at different levels. Various Cu-enzymes (such as amine oxidase, ceruloplasmin, cytochrome-c oxidase, dopamine-monooxygenase, extracellular superoxide dismutase, lysyl oxidase, peptidylglycineamidating monoxygenase, Cu/Zn superoxide dismutase, and tyrosinase) mediate the effects of Cu deficiency or excess. Cu excess can have severe negative impacts. Cu generates oxygen radicals and many investigators have hypothesized that excess copper might cause cellular injury via an oxidative pathway, giving rise to enhanced lipid peroxidation, thiol oxidation, and, ultimately, DNA damage
In the general population, potential sources of Hg exposure include the inhalation of this metal vapor in the air, ingestion of contaminated foods and drinking water, and exposure to dental amalgam through dental care
Nowadays it was well established that iodine deficiency or excess has severe consequences on human health and associated with the presence of TMNs
Compared to other soft tissues, the human thyroid gland has higher levels of I, because this element plays an important role in its normal functions, through the production of thyroid hormones (thyroxin and triiodothyronine) which are essential for cellular oxidation, growth, reproduction, and the activity of the central and autonomic nervous system. As was shown in present study, malignant transformation is accompanied by a significant loss of tissue-specific functional features, which leads to a drastically reduction in I content associated with functional characteristics of the human thyroid tissue. Because the malignant part of gland stopped to produce thyroid hormones, the rest “intact” part of thyroid tries to compensate thyroid hormones deficiency and work more intensive than usual. The intensive work may explain elevated level of I in thyroid tissue adjacent to malignant tumor.
Drastically reduced level of I content in cancerous tissue could possibly be explored for differential diagnosis of benign and malignant thyroid nodules, because, as was found in our ealier studies, thyroid benign trasformation (goiter, thyroiditis, and adenoma) is accompanied by a little loss of I accumulation
An uncontrollable cell proliferation characterize the malignant tumors. Therefore, morphological structures of TMNs differ from the structure of normal thyroid parenchyma. Because K is mainly an intracellular electrolyte, an elevated level of K content in cancerous tissue in comparison with “normal” and “adjacent” tissue might reflect increase of ratio “mass of transformed thyroid cell – mass of follicular colloid” in the malignant tumors. Nevertheless, the accumulation of K in neoplastic thyroids could possibly be explored for diagnosis of TMNs.
Mg is abundant in the human body. This element is essential for the functions of more than 300 enzymes (e.g. alkaline phosphatases, ATP-ases, phosphokinases, the oxidative phosphorylation pathway). It plays a crucial role in many cell functions such as energy metabolism, protein and DNA syntheses, and cytoskeleton activation. Moreover, Mg plays a central role in determining the clinical picture associated with thyroid disease
There is very little information about Rb effects on thyroid function. Rb as a monovalent cation Rb+ is transfered through membrane by the Na+K+-ATPase pump like K+ and concentrated in the intracellular space of cells. Thus, Rb seems to be more intensivly concentrated in the intracellular space of cells. The sourse of Rb elevated level in tumor and adjacent to tumor tissue may be Rb environment overload. The excessive Rb intake may result a replacement of medium potassium by Rb, which effects on iodide transport and iodoaminoacid synthesis by thyroid
It was reported that around 40% of TMNs have some type of calcification
The high level of Se content found just in thyroid tissue adjacent to malignant tumor cannot be regarded as pure chance. The seleno-protein characterized as Se-dependent glutathione peroxidase (Se-GSH-Px) is involved in protecting cells from peroxidative damage. This enzyme may reduce tissue concentration of free radicals and hydroperoxides. It is particular important for the thyroid gland, because thyroidal functions involve oxidation of iodide, which is incorporated into thyreoglobulin, the precursor of the thyroid hormones. For oxidation of iodide thyroidal cells produce a specific thyroid peroxidase using of physiologically generated hydrogen-peroxide (H2O2) as a cofactor
This study has several limitations. Firstly, analytical techniques employed in this study measure only nineteen ChE (Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn) mass fractions. Future studies should be directed toward using other analytical methods which will extend the list of ChE investigated in “normal” thyroid and in pathologically altered tissue. Secondly, the sample size of TMNs group was relatively small and prevented investigations of ChEs contents in this group using differentials like gender, histological types of TMNs, tumor functional activity, stage of disease, and dietary habits of patients with TMNs. Lastly, generalization of our results may be limited to Russian population. Despite these limitations, this study provides evidence on many ChEs level alteration in malignant tumor and thyroid tissue adjacent to tumor and shows the necessity to continue ChEs research of TMNs.
In this work, ChEs analysis was carried out in the tissue samples of TBNs using a combination of three non-destructive methods: EDXRF, INAA-SLR and INAA-LLR. It was shown that this combination is an adequate analytical tool for the non-destructive determination of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn content in the tissue samples of human thyroid in norm and pathology, including needle-biopsy specimens. It was observed that in malignant tissue the mass fraction of Ag, Cl, Co, Cr, Cu, Hg, K, Mg, Na, and Rb are approximately 13, 2.3, 1.4, 1.6, 3.4, 20, 1.6, 1.6, 1.3, and 1.5 times, respectively, higher whereas mass fraction of I is 26 times lower than in the normal thyroid. In a general sense Cr, Cu, Fe, K, Mg, Mn, Na, Sc, and Zn contents found in the “normal” and “adjacent” groups of thyroid tissue samples were very similar. However, in the “adjacent” group mean mass fractions of Ag, Cl, Co, Hg, I, Rb, and Se were approximately 33, 1.6, 1.8, 52, 1.7, 2.3, and 1.3 times, respectively, higher, while mean values of Ca and Sr content were 2 and 4 times lower than in the “normal” group. Significant changes were found in tumor ChEs composition in comparison with thyroid tissue adjacent to tumor. In malignant tumor Ca, Cl, Cu, K, and Sr contents were approximately 2.8, 1.4, 1.8, 1.7, and 5.4 times, respectively, higher, while Ag, Hg, I, and Se content 2.6, 2.6, 43, and 1.5 times, respectively, lower than in “adjacent” group of tissue samples.
Thus, from results obtained, it was possible to conclude that the common characteristics of TMNs in comparison with “normal” thyroid and visually “intact” thyroid tissue adjacent to malignant tumors were elevated levels of Cl and K, as well as drastically reduced level of I. Furthermore, the ChEs composition of thyroid tissue adjacent to tumor did not equal ChEs contents of “normal” thyroid. Moreover, contents of such elements as Ag, Hg, I, and Se in adjacent tissue were higher than in tumor. From here, the excessive accumulation of Ag, Hg, I, and Se by thyroid tissue is likely to precede the TMNs origination and development
It was supposed that elevated levels of Cl and K, as well as drastically reduced level of I in cancerous tissue could possibly be explored for differential diagnosis of benign and malignant thyroid nodules
The author has not declared any conflict of interests.
The author received no financial support for this study and for publication of this article.
The author is extremely grateful to Profs. B.M. Vtyurin and V.S. Medvedev, Medical Radiological Research Center, Obninsk, as well as to Dr. Yu. Choporov, former Head of the Forensic Medicine Department of City Hospital, Obninsk, for supplying thyroid samples.