Biomedical subjects
Publications and source records attributed to J Kanitakis.
Milia-like idiopathic calcinosis cutis is a rare entity. Only 17 cases have been reported so far. Two-thirds of these have been associated with Down syndrome. We report the fifth case occurring in a child without Down syndrome. Milia-like idiopathic calcinosis cutis has long been regarded as a peculiar subtype of idiopathic calcinosis cutis. The pathogenesis of the disorder remains unclear.
The T (Thomsen-Friedenreich) antigen and its precursor, the Tn antigen, are complex mucin-type carbohydrate antigens, the expression of which seems to be correlated with prognosis in some human cancers. We studied comparatively the immunohistochemical expression of these antigens in a series of primary and locally recurring squamous cell carcinomas developing in the skin of immunosuppressed (organ-transplanted) patients. 10/26 tumours were completely unreactive for both antigens; among the remaining cases, 10/14 (71%) of recurring and 6/12 (50%) of primary tumours showed a higher expression of the precursor (Tn antigen) as compared with the T antigen. Since recurring tumours are more likely to spread metastatically, our results upheld the contention that a higher expression of the Tn antigen is correlated with a more aggressive course of cutaneous squamous cell carcinomas.
Keratin 15 (K15) was recently shown to be a specific marker of stem cells of the hair-follicle bulge. We studied the reactivity of an antibody to the CD8 antigen (C8/144B), recognizing K15, on 66 cutaneous tumors with known or alleged pilar differentiation, in order to assess its usefulness in the diagnosis of this group of tumors. 2/2 basal cell nevi, 5/8 trichoepitheliomas and 1/3 trichofolliculomas showed substantial reactivity. Much weaker reactivity was observed in cases of trichilemmal tumors (trichilemmomas and trichilemmal cysts); by contrast, all cases of pilomatricomas, basal cell carcinomas and epidermoid cysts were completely unreactive. These results are in keeping with the admitted differentiation of the tumors studied, and suggest further that basal cell carcinomas do not differentiate towards hair bulge cells. From a practical point of view, immunostaining for K15 seems to be an additional useful adjunct for the differential diagnosis between basal cell carcinoma and trichoepithelioma.
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BACKGROUND: Basement membrane (BM) antigens and matrix metalloproteinases (MMP) are involved in tumor invasion and metastasis. Basal (BCC) and squamous cell carcinomas (SCC) differ with respect to their biological behavior since the former are only locally aggressive whereas the latter have a metastatic potential. MATERIALS AND METHODS: We studied the immunohistochemical expression of several BM antigens and of MMP2 and MMP9, in 13 BCC, 13 SCC, and 8 in situ skin carcinomas. RESULTS: The expression of most BM antigens was reduced in the tumors in comparison with normal skin. Hemidesmosome- and lamina lucida-associated antigens (plectin, NUT2, alpha 6/CD49f and laminin-5) were more decreased in BCC, whereas collagens type VII and IV were more decreased in SCC as compared with BCC; in BCC and SCC both collagens tended to be decreased on the leading edge of invasive tumor masses. In situ carcinomas showed a slightly diminished expression of alpha 6/CD49f integrin, plectin and NUT2. The expression of both MMP2 and MMP9 was increased in SCC as compared with BCC. CONCLUSION: Our findings further upheld the role of BM antigens and MMPs in the process of tumor aggressiveness. The reduced expression of collagen IV, combined with an increased expression of both MMP2 and MMP9 could account for the increased metastatic potential of SCC vs BCC through an increased invasion of the extracellular matrix and the vascular space.
BACKGROUND: The CD10 (or CALLA) antigen is a neutral endopeptidase expressed by a variety of non-hemopoietic cells, including fibroblasts in various tissues. So far little or conflicting data exist concerning the expression of CD10 in normal and pathologic skin. METHODS: We investigated the immunohistochemical expression of the CD10 antigen on formalin-fixed, paraffin-embedded tissue specimens of normal skin and 162 cutaneous proliferative lesions, mostly mesenchymal tumors. RESULTS: In normal skin CD10 immunoreactivity was found in periadnexal mesenchymal cells. In skin tumors, CD10+ cells were found mainly in dermatofibromas and, to a lesser extent, in Dermatofibrosarcoma protuberans and neurofibromas. Metastatic (and to a lesser extent primary) melanomas also occasionally expressed CD10. CONCLUSION: Our results show that the CD10 antigen is expressed by mesenchymal cells of normal human dermis, presumably encompassing a subset of CD34+ dermal dendrocytes and/or periadnexal fibroblasts. The CD10 antigen could be used as an adjunct to the diagnosis of some spindle-cell cutaneous tumors such as dermatofibromas and Dermatofibrosarcoma protuberans, but its value as a single marker is rather limited. The possible role of CD10 as a progression marker in melanoma is interesting and merits further study.
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The immunohistochemical expression of neuron-specific enolase (gamma/gamma) (NSE) was studied comparatively with S100 protein in a group of Langerhans-cell-type ("X") (n = 8) and non-Langerhans-cell-type ("non X") (n = 24) cutaneous histiocytoses. NSE was expressed by the majority (70-90%) of histiocytic cells in all cases of Langerhans-cell histiocytoses, whereas it was absent from non-Langerhans-cell histiocytoses. S100 protein was expressed by the majority of Langerhans-cell histiocytosis cells but also by a small percentage (1-5%) of cells in non Langerhans-cell histiocytoses. These results show that NSE is almost as sensitive as, but more specific than, S100 protein in discriminating Langerhans-cell from non-Langerhans cell cutaneous histiocytoses, and that it consequently represents a useful adjunct in the immunohistochemical diagnosis of histiocytic skin diseases.
Cyclosporin A, a potent immunosuppressive drug currently used in organ transplant recipients, has been shown to exert in vitro a direct antiproliferative effect on a number of cell types present in the skin, including keratinocytes, fibroblasts, and endothelial cells. Although in vitro studies suggest that cyclosporin A may interfere with the functional capacities of epidermal Langerhans cells, there is no evidence that the treatment influences the distribution or number of Langerhans cells in vivo. We used a model of normal human skin graft to "nude" mice, which is free of the human systemic control mechanisms, for studies on the DNA synthesis of human Langerhans cells under the influence of cyclosporin A. The grafted animals were given daily subcutaneous (50 mg/kg) or intraperitoneal (5, 12.5, and 25 mg/kg) drug injections during three weeks, which resulted in mean blood levels comparable to those observed in treated patients with organ transplants or psoriasis, respectively. BrdU administered during the last week of the experiment was incorporated by all cells synthesizing DNA, including those passing through S-phase. Langerhans cells were detected on deparaffinized or frozen tissue sections of xenografts with anti-CD1a and anti-HLA DR monoclonal antibodies, and the number of BrdU-positive cells was determined by double labeling. Our results indicate that the Langerhans cell DNA synthesis is impaired by therapeutic levels of cyclosporin A.
Ciclosporin A (CsA) is a cyclic undecapeptide of fungal origin endowed with immunosuppressive properties but also active on cells outside the immune system, especially epidermal and hair-follicle keratinocytes. Its wide clinical use for the prevention of organ graft rejection has led to the discovery of its beneficial effect in some dermatoses, mainly psoriasis, by a mechanism that still remains largely speculative. Treatment with CsA induces cutaneous and extracutaneous side-effects; whereas some of these are relatively benign and regressive upon treatment discontinuation, others (notably nephrotoxicity) are potentially serious and may require CsA withdrawal. The topical use of CsA has generally proven ineffective, but ongoing studies will hopefully result in the discovery of forms (or analogues) that are active in local applications.
Bullous pemphigoid (BP) is an auto-immune blistering skin disease associated with the presence of autoantibodies directed to BP antigens located at the basement membrane zone of the dermal-epidermal junction. The present study was designed to test for the involvement of cellular immune mechanisms in the pathogenesis of blister formation. An immunohistochemical analysis of the lesional, peri-lesional, and pre-lesional mononuclear cell infiltrates, performed in 7 BP patients, revealed the following observations: 1) all the skin biopsies contained a high percentage of mononuclear cells within the inflammatory cellular infiltrate; 2) T cells (CD3+, CD45RO+), with a phenotype of activated helper T cell (CD4+, CD25+) were consistently found; 3) T cells were found beneath the bullae but, more importantly, also at the dermal-epidermal junction in close contact with the basement membrane zone in pre- and peri-bullous lesions. These results show that activated T cells are found at the early phase of the onset of BP lesions and suggest that they could play a role, in association with autoantibodies, in the pathogenesis of bulla formation.
p53 is a tumour-suppressor gene, mutations of which are found in malignant skin lesions. We studied the immunohistochemical expression of the (mutated) p53 protein in 17 cases of Paget's disease (12 mammary and 5 extramammary). Four of the mammary specimens (33.3%) expressed p53 within Paget's cells; in one of these an underlying ductal adenocarcinoma was present and this was also p53-positive. All extramammary cases proved p53-negative. These results underline the differences that exist between mammary and extramammary Paget's disease and favour the origin of the former from the underlying adenocarcinoma rather than the surface epithelium.
Peripherin is a neuronal intermediate filament reportedly expressed in neuroendocrine skin carcinomas and some melanocytic tumors. In order to assess the diagnostic usefulness of antibodies to peripherin in dermatopathology, we studied its expression in 68 skin tumors mostly of neural origin, and compared this expression with that of neurofilaments, a well-established neuronal marker. Antibodies to peripherin and neurofilaments both labeled dermal neurons present in normal skin and within the tumors. Specific labeling of tumor cells for peripherin was seen in only 2/5 neuroendocrine skin carcinomas, 3/18 benign nevi and 7/19 melanomas; even in these cases the percentage of tumor cells did not exceed 20%. We conclude that antibodies to peripherin may be used for the demonstration of cutaneous neurons in normal and diseased skin; however their diagnostic usefulness appears limited, less than that of antibodies to neurofilaments.
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