Abstract

Metallothioneins (MT) are low-molecular weight proteins implicated in heavy metal detoxification, zinc and cooper homeostasis and cell protection against free radicals. In variety of cancers MT-overexpression was shown, but there are just a few studies on the role of MT in skin carcinogenesis. Current study was undertaken to evaluate MT and Ki-67 expression in pre-cancerous skin lesions as well as in fully developed skin cancers. 73 squamous cell carcinomas (SCC), 23 actinic keratoses (AK) and 20 normal skin samples were included in the study. In obtained paraffin sections immunohistochemical reactions were performed. MT-expression in SCC (mean 2.89 ± 1.83) was significantly higher than in AK (mean 1.69 ± 1.26)(p = 0.006) and higher than in normal skin (mean 2 ± 0.79) (p = 0.0075). The MT-expression positively correlated with Ki-67 expression (R = 0.28; p = 0.017) in SCC and in AK (R = 0.49; p = 0.018). Various clinico-pathological variables, e.g. morphology, size of lesions and the depth of neoplastic infiltration were not associated to MT-expression in both SCC and AK. The grade of histological differentiation of SCC correlated positively with Ki-67 antigen (p < 0.001) and did not correlate with MT-expression (p = 0.06). Ki-67 expression was higher in SCC and in AK than in healthy skin (p = 0,003). In SCC and in AK expression of Ki-67 antigen correlated positively with MT-expression (respectively p = 0.017 and p = 0.018). MT may serve as a good markers of proliferation in SCC and AK. MT-overexpression in SCC may suggest a potential role of MT in skin carcinogenesis.

Highlights

  • Metallothioneins (MT I-IV), small cysteine-rich, metalbinding proteins, have been described in number of organs, including the skin [1, 2]

  • Significant differences were observed in localization of MTpositive cells in normal skin, in actinic keratoses (AK) and in squamous cell carcinomas (SCC) (p

  • In healthy skin MT-expression was revealed in epidermal basal layer, hair matrix cells and outer hair root sheath, some cells of sebaceous and eccrine glands

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Summary

Introduction

Metallothioneins (MT I-IV), small cysteine-rich, metalbinding proteins, have been described in number of organs, including the skin [1, 2]. High levels of MT-I and II, the most widely expressed isoforms, are found in liver, kidneys and skin, MT-III is predominantly expressed in brain, while MT-IV has been identified in squamous epithelia of alimentary tract [3,4,5]. The main function of MT is their contribution in zinc and copper homeostasis in cells and tissues. These metallic ions, being the part of proteins and enzymes (e.g. zinc-dependent transcription factors or p53 protein), are crucial for proper cell metabolism and differentiation [2, 6]. Some researchers [15, 17, 18] suggested that less differentiated, anaplastic tumor cells were linked to higher MT expression, indicating for MT as a potential and important prognostic factor. It was proved that the overexpression of MT in tumor cells was responsible for the development of resistance to anticancer drugs and radiotherapy [9, 22]

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