metallothionein and Carcinoma--Basal-Cell

Basal cell carcinoma (BCC) is the most frequent skin cancer, with many different histological subtypes. Recent studies have investigated the expression of proliferative markers, but little is known about the expression of metallothioneins (MT) in different histological subtypes of this cancer and their impact on proliferation intensity in BCC. In this study, we examined MT-I/II expression by immunohistochemistry in 58 different histological subtypes of BCC (38 nodular, six adenoid, eight infiltrative, and six metatypic cases) and correlated its expression with tumor size and Ki-67 proliferation rate. Statistical analysis revealed no significant differences in the expression of studied markers in regard to the histological subtype. A positive correlation between MT and Ki-67 expression was observed for all the studied cases (r = 0.26; p = 0.049), but was even stronger in the metatypic subtype of BCC (r = 0.85; p = 0.033). MT and Ki-67 expression did not correlate with tumor size. In conclusion, it seems that metallothioneins may have an impact on the proliferation rate of BCC,but further studies are required to determine whether MT may be a risk factor of recurrences.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Cell Nucleus; Humans; Immunohistochemistry; Ki-67 Antigen; Metallothionein; Middle Aged; Skin Neoplasms; Young Adult

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent skin cancer. Its pathogeny is linked to genotoxic effects of actinic radiation exposure, especially to ultraviolet wavelength. Metallothionein (MT) is a low-molecular weight protein with high affinity for heavy metal. Its intracellular function has been related to heavy metals and free-radical detoxification, although many studies linked MT to protective action against actinic mutagenesis. In other way, overexpression in malignant tumors has been related to worse prognosis. We aimed to evaluate MT immunohistochemical expression in skin cancer associated to actinic radiation. Twenty-six BCC cases, 20 SCC, and 6 normal skin fragments were investigated. Immunohistochemical assay were performed by streptavidin-biotin-peroxidase technique with standard monoclonal antibody (E9). In normal skin, immunostaining was observed in basal layer of the epithelium. In the epithelium adjacent to tumors, suprabasal layer was also intensely labeled. Mean MT immunostaining indices were 18.5+21.2% for BCC and 69.1+14.4% for SCC. This difference was statistically significant. Higher MT expression in SCC as compared with BCC suggests association with tumoral aggressiveness.

Topics: Aged; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Male; Metallothionein; Skin Neoplasms; Ultraviolet Rays

Epidermal changes overlying dermatofibromas (DFs) have been described as ranging from psoriasiform simple hyperplasia to basaloid hyperplasia sometimes morphologically indistinguishable from superficial basal cell carcinoma (BCC). To characterize epidermal hyperplasia overlying DFs and to determine its association with the disease process, we examined 30 cases of DF showing hyperplastic epidermis. We used nine immunohistochemical markers associated with keratinocyte proliferation or differentiation. In DFs, the dermal metallothionein (MT) expression and immunophenotypic changes with regard to epidermal differentiation varied depending on the stage of lesional evolution of the DFs. Immunostaining for epidermal growth factor receptor (EGFR), MT, and keratin 6 (K6) increased in simple hyperplastic epidermis (SHE) overlying DFs (n = 11), whereas it gradually diminished in basaloid hyperplastic epidermis (BHE) overlying DFs (n = 19). In SHE, there was a significant increase in K14 expression. Among 19 BHE cases, 12 showed premature expression of involucrin and delayed appearance of K1 along with aberrant expression of K14. Conversely, the remaining 7 BHE cases showed a pattern of involucrin and K1 similar to that of normal skin coinciding with decreased or absent dermal MT expression. Loricrin and filaggrin expression in all DFs was the same as that of normal skin. Based on the sparse positivity of Ki-67 in the hyperplastic epidermis overlying DFs, we found that the biologic ability of BHE and SHE was not apparent in the hyperproliferative state observed in psoriasis and BCC. These results suggest that the dermal fibrohistiocytic process may trigger the induction of SHE overlying DFs by an unknown mechanism and then mediate both the abnormal keratinocyte differentiation and the transformation of SHE to BHE through the evolution of the dermal lesions.

Topics: Biomarkers; Carcinoma, Basal Cell; Cell Differentiation; Cell Division; Epidermis; ErbB Receptors; Filaggrin Proteins; Histiocytoma, Benign Fibrous; Humans; Hyperplasia; Immunoenzyme Techniques; Keratinocytes; Keratins; Metallothionein; Precancerous Conditions; Psoriasis; Skin Neoplasms

Basaloid proliferations overlying dermatofibromas which morphologically resemble superficial basal cell carcinomas have been interpreted as both reactive/regressive and frankly malignant. Metallothioneins (MTs) are low-molecular-weight proteins with a selective binding affinity for heavy metal ions. MTs has been proposed to represent a biological marker of carcinogenesis and, in a variety of human tumours, a correlation between immunohistochemically overexpression of MT and aggressive clinical behaviour has been shown. In order to clarify the nature of basaloid proliferations overlying dermatofibromas, we examined, immunohistochemically, 10 dermatofibromas with overlying simple hyperplasia, 16 dermatofibromas with overlying basaloid proliferation, and 35 basal cell carcinomas, for expression of MT. In normal epidermis, the basal keratinocytes showed cytoplasmatic MT immunoreactivity. The staining intensity was stronger in the basal cells of the rete ridges, an observation which is in accordance with the high proportion of S-phase cells in this area. Simple hyperplasia showed the same MT expression pattern as normal epidermis. Basaloid proliferations stained like superficial and nodular basal cell carcinomas. Of nodular basal cell carcinomas, 92% (12 of 13) showed decreased/absent MT immunoreactivity, while 86% (six of seven) of infiltrating/morphoea-like basal cell carcinomas showed overexpression of MT (P = 0.001, Fisher's exact test). The results demonstrate that MT overexpression in basal cell carcinomas is correlated with infiltrative growth pattern. The similar expression of MT in basaloid proliferations and 'non-infiltrating' basal cell carcinomas suggests that these lesions share a common change in metabolism and/or differentiation.

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Division; Epidermis; Histiocytoma, Benign Fibrous; Humans; Hyperplasia; Immunoenzyme Techniques; Keratinocytes; Metallothionein; Skin Neoplasms