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Zaichick et al. J Cancer Metastasis Treat 2018;4:60 I http://dx.doi.org/10.20517/2394-4722.2018.52 Page 9 of 15

we found a significant age-related increase of Br content in human thyroid [23,26-28] . Therefore, a goitrogenic
and, probably, carcinogenic effect of excessive Br levels in the thyroid of old females was assumed. On the
one hand, elevated levels of Br in TC tissues, observed in the present study, support this conclusion. But, on
the other hand, bromide compounds, especially KBr, NaBr, and NH Br are frequently used as sedatives in
4
[83]
Russia . It may be the reason for elevated levels of Br in specimens of patients with TC. Nevertheless, the
accumulation of Br in neoplastic thyroid tissues could possibly be explored for diagnosis of TC.
Ca
In addition to the elevated Br level, an excess in Ca mass fractions in thyroid tissue may contribute to
harmful effects on the gland. Many reviews and numerous papers raise the concern about role of Ca in the
prostate, breast, lung and other organ malignant transformation [84-94] .

Cl
Cl is a ubiquitous, extracellular electrolyte essential to more than one metabolic pathway. Cl exists in the
form of chloride in the human body. In the body, it is mostly present as sodium chloride. Therefore, as usual,
there is a correlation between Na and Cl contents in tissues and fluids of human body. It is well known
that Cl mass fractions in samples depend mainly on the extracellular water volume, including the blood
[95]
volumes, in tissues . Cancerous tissues are predominantly highly vascularized lesions. Thus, it is possible to
speculate that thyroid malignant tumors are characterized by an increase of the mean value of the Cl mass
fraction because the level of tumor vascularization is higher than that in normal thyroid tissue. Overall, the
elevated levels of Cl in neoplastic thyroids could possibly be explored for diagnosis of TC.

Cu
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 SOD, lysyl oxidase, peptidylglycineamidating monoxygenase, Cu/Zn SOD, 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 [96-98] . Thus, Cu accumulation in thyroid parenchyma with age may be involved in oxidative stress,
dwindling gland function, and increasing risk of goiter or cancer [26,28] . The significantly elevated level of Cu
in thyroid malignant tumors, observed in the present study, supports this speculation. However, an overall
comprehension of Cu homeostasis and physiology, which is not yet acquired, is mandatory to establish the
exact role of Cuin the thyroid malignant tumors etiology and metabolism. Anyway, the accumulation of Cu
in neoplastic thyroids could possibly be explored for diagnosis of TC.

I
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. Malignant transformation is accompanied by a loss of tissue-
specific functional features, which leads to a significant reduction in I content associated with functional
characteristics of the human thyroid tissue. Drastically low level of I content in neoplastic thyroids could
possibly be explored for diagnosis of TC.

K
An uncontrollable cell proliferation characterizes the malignant tumors. Therefore, morphological structures
of TC tissue differ from the structure of normal thyroid parenchyma. Because K is mainly an intracellular
electrolyte, an elevated level of K content in the TC tissue might reflect the increase of ratio “mass of