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The role of serum zinc and copper levels in predicting malignancy in differentiated thyroid cancers

Trace Elements and Electrolytes

Dustri-Verlag Dr. Karl Feistle

thyroid cancer, copper, zinc

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      Abstract

      Abstract. Objective: The incidence of papillary thyroid cancer (PTC) is rising all over the world. The trace elements copper (Cu) and zinc (Zn) are essential for many physiological functions. Concurrent exposure to Cu and Zn may result in remarkable epithelial toxicity and stress. We evaluate the serum Cu and Zn concentrations as well as the Cu/Zn ratio to predict the possible malignancy of PTC in patients who underwent thyroid fine needle aspiration biopsy (FNAB) before total thyroidectomy. Material and methods: Serum Zn and Cu concentrations as well as the Cu/Zn ratio of 111 patients (23 male and 89 female) who underwent total thyroidectomy and in whom preoperative thyroid FNAB was non-diagnostic or demonstrated atypia of undetermined significance (AUS) or was suspicious for follicular neoplasm (SFN) or showed benignity were evaluated. Postoperative pathology results were classified as benign or malignant. The amount of Cu and Zn was determined using atomic absorption spectrometry. In the malignant group, preoperative serum Cu levels correlated with tumor size, localization, and focality. Results: In the malignant group, the preoperative Cu level and Cu/Zn ratio was found higher than in the benign group; also postoperative serum Cu difference and serum Cu/Zn difference showed a significant decrease when compared to the preoperative state (p = 0.001, 0.034, 0.002, 0.003, respectively). In receiver-operating characteristics (ROC) analysis, the optimal cut-off value of preoperative Cu for differentiating malignant tumor from benign tumor was found to be 158.88 mg/dL (p = 0.001; sensitivity: 48%, specificity: 84%). In subjects in whom FNAB results were non-diagnostic or revealed benignity, AUS, or SFN, preoperative Cu levels over 158.88 µg/dL to predict malignancy were found to have a sensitivity of 24%, 67%, 54%, and 50%, respectively, and a specificity of 70%, 82%, 93%, and 100%, respectively. Conclusions: Before thyroid surgery, if FNAB was non-diagnostic or revealed indeterminate cytology like AUS and SFN, the assessment of serum Cu is considered to be a useful diagnostic tool for surgical decisions in patients with thyroid nodules and for determining PTC cases.


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      Copper and carcinogenesis.

      Metal ions play an important role in biological systems, and without their catalytic presence in trace or ultratrace amounts many essential co-factors for many biochemical reactions would not take place. However, they become toxic to cells when their concentrations surpass certain optimal (natural) levels. Copper is an essential metal. Catalytic copper, because of its mobilization and redox activity, is believed to play a central role in the formation of reactive oxygen species (ROS), such as O2-* and *OH radicals, that bind very fast to DNA, and produce damage by breaking the DNA strands or modifying the bases and/or deoxyribose leading to carcinogenesis. The chemistry and biochemistry of copper is briefly accounted together with its involvement in cancer and other diseases.
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        Serum ceruloplasmin and copper levels in patients with primary brain tumors.

        Serum copper and ceruloplasmin levels are known to increase in several malignancies such as osteosarcomas, some gastrointestinal tumors, and lung cancer. In this study serum copper and ceruloplasmin levels in 40 patients with primary brain tumors were studied. Both parameters were increased in sera of patients with tumors in comparison with healthy subjects or patients with non-tumorous neurological diseases. It is concluded that copper and ceruloplasmin represent a good complement to some other nonspecific parameters in evaluating the activity of malignancy and the therapeutic results.
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          Interleukin 7 is produced by murine and human keratinocytes

          Interleukin 7 (IL-7) was originally identified as a growth factor for B cell progenitors, and subsequently has been shown to exert proliferative effects on T cell progenitors and mature peripheral T cells as well. Constitutive IL-7 mRNA expression so far had been demonstrated in bone marrow stromal cell lines, thymus, spleen, and among nonlymphoid tissues in liver and kidney. Here we show that both murine and human keratinocytes express IL-7 mRNA and release IL-7 protein in biologically relevant amounts. The physiological or pathological relevance of keratinocyte-derived IL-7 is presently unknown. Our finding that keratinocytes can produce IL-7 in concert with reports that IL-7 is a growth factor for in vivo primed antigen- specific T cells, as well as for T lymphoma cells suggests, however, that keratinocyte-derived IL-7 is important in the pathogenesis of inflammatory skin diseases and cutaneous T cell lymphoma.
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