Metallothionein expression in basaloid proliferations overlying dermatofibromas and in basal cell carcinomas

Abstract

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.

Metallothionein – overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients

“…In the last decade, several reports disclosed MT overexpression as a useful prognostic factor for tumour progression and drug resistance in a variety of cancers such as ovarian cancer (Surowiak et al, 2005), renal cell carcinoma (Mitropoulos et al, 2005), breast cancer (Jin et al, 2004), non-small-cell lung carcinomas (Dziegiel et al, 2004), acute lymphoblastic leukaemia (Sauerbrey et al, 1994), pancreatic carcinoma (Ohshio et al, 1996) or carcinoma of the gallbladder (Shukla et al, 1998). Similar results could be found in smaller retrospective studies in melanoma and nonmelanoma skin cancers (Zelger et al, 1993(Zelger et al, , 1994Rossen et al, 1997;Goldmann et al, 1998;Sugita et al, 2001). In some other tumours such as colorectal and bladder cancer, MT overexpression was not correlated with increased malignancy Jasani and Schmid, 1997).…”

Expression of metallothionein I/II and Ki-67 antigen in various histological types of basal cell carcinoma

“…A similar form of MT expression was demonstrated in a hypertrophic epidermis. Basaloidal proliferations, as well as superficial and nodular forms of BCC, demonstrated a decreased MT-I/II expression (in approximately 92% of the cases) [20]. Nevertheless, in 86% of cases of infiltrating BCC, increased expression of MT-I/II was demonstrated in neoplastic cells [20].…”

“…Rossen et al analyzed levels of expression of MT-I/II isoforms in BCC compared to normal epidermis and benign epidermal hypertrophy, including basaloidal hypertrophy, covering solid fibromas [20]. Within normal epidermis, the expression of MT-I/II was documented in cytoplasm of basal cells.…”

“…Until now, only individual studies have been published in which MT expression was studied in skin cancers [20,21]. The studies showed an increased expression of MT in spinocellular carcinoma and a less typical increased expression of MT in aggressive varieties of BCC, but none of the investigations dealt with the relationship between expressions of MT and Ki-67 antigen in various histological types of BCC.…”

Histologic Mimics of Basal Cell Carcinoma

“…Studies have had mixed results regarding the utility of Ki-67 and p53 for distinguishing BCC from FI. 25,28,[39][40][41] Similar to benign follicular tumors, FI will demonstrate colonization by CK20…”