Expression of Stromelysin 3 in Keratoacanthoma and Squamous Cell Carcinoma

Abstract

Stromelysin 3 (ST3) is a member of the metalloproteinase family, which is expressed in the skin during wound healing and in the stroma of basal cell carcinoma. A high level of expression of ST3 has been observed in carcinomas of poor prognosis. In benign tumors, though, ST3 is not expressed or is at a low level. We have immunohistochemically studied the expression of ST3 in 89 randomly selected cases of squamous cell carcinomas (SCCs), 104 of keratoacanthomas (KA), and 23 cases of metastatic SCC. Stromelysin 3 was expressed only by fibroblasts surrounding the tumors and not by epithelial cells. The proportion of tumors positively stained was 22% of KA, 47% of randomly selected SCC, and 70% of metastatic SCC. In areas of poorly demarcated neoplastic cells, a reinforcement of the staining was observed in the stroma. The intensity and dispersion of staining were used to determine the level of expression. There were significantly more SCC in the groups of high expression levels, and both parameters were significantly higher in SCC than in KA. Expression of ST3 in benign tumors is unusual. Its expression in the the stroma of keratoacanthomas can be related to the high tissue remodeling activity observed in these tumors. It also could be interpreted as in favor of the neoplastic nature of KA. Nevertheless, the level of expression was higher in SCC than in KA and seemed to be related to the prognosis of these tumors. These results correlate well with those obtained in breast cancers and in noncutaneous SCC.

Transformation-specific matrix metalloproteinases, MMP-7 and MMP-13, are present in epithelial cells of keratoacanthomas

“…Furthermore, MMP-11 was detected in fibroblasts surrounding 22% of examined keratoacanthomas. 30 We have recently shown that also MMP-26 is present in the pushing border of keratoacanthomas. 11 As the expression of MMP-2, -7, -8, and -13 has previously been detected in malignantly transformed human keratinocytes 10,17,31,32 in SCCs, but not in normal migrating keratinocytes, we chose them to begin with.…”

Differential molecular profiling between skin carcinomas reveals four newly reported genes potentially implicated in squamous cell carcinoma development

“…A number of them (i.e. fibronectin, biglycan, stromelysin 3, tenascin) have already been reported as overexpressed during carcinogenesis and/or metastasis including skin carcinogenesis (Asch et al, 1999;Thomas et al, 2001), which again comforts our gene selection procedure. Genes involved in cell adhesion are known to be modulated in different tumors.…”

Differentiating Squamous Cell Carcinoma from Keratoacanthoma Using Histopathological Criteria

“…The following criteria were then determined in all samples (answer: presence/absence): rounded shape (arciform disposition) of the lower part of the tumor [25]; sharp outline between the stroma and the proliferating epithelium; central crater filled with keratin [1, 26]; presence of at least one epithelial ‘lip’ at the lateral part of the tumor [[; clear]; intraepithelial elastic fibers (visible with standard staining) [27, 28, 29, 30]; intraepithelial polymorphonuclear abscesses [5]; ulceration [5]; extension more lateral than downward [24]; extension beyond sweat glands [4]; marked pleomorphism or anaplasia [22]; parakeratosis; dyskeratosis [23]; more than 2 mitoses per high-power field (×40) [23, 24, 30]. …”

“…DNA image cytometry [19]or flow cytometry [20, 21]was also proposed to differentiate the two tumors. We have recently shown that stromelysin 3 expression is more intense in SCC than in KA and could be a marker of the biological behavior, since staining was even stronger in those cases of SCC which led to metastasis [22]. …”