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.
Subject(s)
Biomarkers, Tumor/biosynthesis , Carcinoma, Squamous Cell/metabolism , Keratosis, Actinic/metabolism , Metallothionein/biosynthesis , Skin Neoplasms/metabolism , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Female , Humans , Immunohistochemistry , Ki-67 Antigen/metabolism , Male , Metallothionein/metabolism , Middle AgedABSTRACT
INTRODUCTION: Psoriasis is characterized by hyperproliferation and abnormal differentiation of keratinocytes,by the presence of inflammatory cell infiltrate in both the dermis and the epidermis and by alterations of capillaries. p53 protein is an important transcription factor which plays a central role in cell cycle regulation mechanisms and cell proliferation control. OBJECTIVES: This study was performed to identify the expression and localization of p53 protein in lesional and non-lesional skin samples taken from psoriatic patients in comparison with healthy controls. MATERIAL AND METHODS: Sections of psoriatic lesional and non-lesional skin (n=18) were examined. A control group (n=10) of healthy volunteers with no personal and family history of psoriasis was also examined. The expression of p53 was demonstrated using the avidin-biotin complex immunoperoxidase method and the monoclonal antibody DO7. The count and localization of cells with stained nuclei was evaluated using a light microscope in 10 fields for every skin biopsy. RESULTS: In lesional psoriatic skin the count of p53 positive cells was significantly higher than in the skin samples taken from healthy individuals (p<0.01) and non-lesional skin taken from psoriatic patients (p=0.02). No significant difference between non-lesional psoriatic skin and normal skin was observed (p=0.1). A strong positive correlation between mean count and mean per cent of p53 positive cells was found (p<0.0001). P53 positive cells were located most commonly in the basal layer of the epidermis of both healthy skin and non-lesional psoriatic skin. In lesional psoriatic skin p53 positive cells were present in all layers of the epidermis. CONCLUSION: P53 protein appears to be an important factor in the pathogenesis of psoriasis.