Increased tenascin expression in melanocytic tumors

Tenascin is a large extracellular matrix glycoprotein which is widely distributed in normal, hyperplastic and neoplastic tissues. Its function is unknown but it has been associated with the epithelial-stromal interactions, such as cell adhesion and movement which take place, e.g. in morphogenesis, cellular proliferation and neoplasia. In this study, we investigated tenascin expression in 70 benign, dysplastic and malignant melanocytic tumors by using immunohistochemistry and monoclonal anti-tenascin L43DB7C8 antibody on paraffin sections. In all types of benign nevi, both intradermal, compound and functional, there was a moderate expression of tenascin at the dermoepidermal junction and in the papillary dermis. In dysplastic nevi, the fibrotic areas in the papillary clermis also showed a moderate staining for tenascin. Invasive malignant melanomas showed the strongest expression of tenascin. In addition to the staining at the dermo-epidermal junction and in the papillary clermis, there was a variable expression of tenascin in the reticular dermis. Intracyloplasmic tenascin was detected both in primary melanomas and melanoma metastases. In conclusion, we have shown that tenascin expression is moderately increased in benign and dysplastic melanocytic tumors and greatly increased in malignant melanomas and melanoma metastases. The function of tenascin may be related to the cellular-stromal interactions and it is possibly associated with the proliferation and spread of the melanocytic tumors.     

Tenascin expression in hyperproliferative skin diseases

The expression of tenascin, a recently discovered extracellular matrix glycoprotein, was studied by immunohistochemistry in normal human skin and in a number of skin diseases with epidermal hyperproliferation such as psoriasis, basal cell carcinoma, Bowen's disease and solar keratosis. Tenascin expression in the upper dermis of normal skin was found to vary from almost absent to patchy along the basal membrane. Staining was continuous and intense around blood vessels, hair follicles and eccrine sweat ducts. In basal cell carcinoma a marked expression of tenascin was found in the tumour stroma, especially adjacent to the basal membrane surrounding the tumour cell nests. In Bowen's disease and solar keratosis, tenascin expression was found in the dermis next to the keratinocytes. In psoriasis the dermal papillae of clinically involved skin were intensely stained and a continuous band of tenascin was present in the upper dermis along the basal membrane. The distribution of tenascin differed from other known extracellular matrix components.     

Tenascin expression in basal cell carcinoma

Tenascin (hexabrachion, cytotactin) is an extracellular matrix glycoprotein whose expression is strongly increased in hyperproliferative skin diseases, as shown by immunohistochemistry with polyclonal sera. In this study we describe a new monoclonal antibody (T2H5) against human tenascin. The specificity of T2H5 was validated by sequential immunoprecipitation of tenascin with polyclonal sera. T2H5 was used to analyse the presence of tenascin in basal cell carcinoma. Using Western blotting, at least two forms of tenascin were found, with approximate molecular weights of 210 and 300 kDa. In cultured human skin fibroblasts only the high molecular weight form was found.     

Coordinate upregulation of tenascin C expression with degree of photodamage in human skin

Tenascin C is a large extracellular matrix glycoprotein involved in morphogenesis and wound healing. The distribution and expression levels of tenascin were examined in photodamaged skin to investigate the hypothesis that photoaged skin displays characteristics of wound repair. In situ hybridization and semiquantitative immunohistochemistry were performed on paired skin biopsies from patients with varying levels of photodamage, using monoclonal antibodies and cRNA probes for tenascin and its large isoform. In sun-protected skin, tenascin protein was distributed adjacent to the dermoepidermal junction, usually sparsely and discontinuously; tenascin mRNA was detected in dermal fibroblasts and some keratinocytes. In photodamaged skin, tenascin protein was increased in proportion to the clinical level of photodamage (analysis of variance: P < 0.0001, n = 29). With increased photodamage, tenascin protein expression became continuous along the dermoepidermal junction, extending deeper into and sometimes throughout the papillary dermis; tenascin mRNA was detected throughout the epidermis. Large tenascin isoform protein and mRNA distribution mirrored that of pantenascin, suggesting that it may be the predominant species in photodamaged skin. There was no correlation between tenascin expression levels and age or sex, and no seasonal variation was noted. The results indicate that photodamaged skin demonstrates tenascin increases consistent with an early wound healing response. However, tenascin increases in photodamage appear to be permanent and may therefore interfere with effective repair of ultraviolet-induced damage. In conclusion, this study has shown that dermal tenascin expression increases in proportion to the degree of photodamage. In normal skin, the temporal and spatial patterns of tenascin expression during morphogenesis and tissue remodelling are crucial to their correct progression. In photoageing, the 'normal' control of tenascin expression seems to be abrogated.     

Dermo-epidermal separation is associated with induced tenascin expression in human skin

Tenascin, a large glycoprotein of the extracellular matrix, shows a site-restricted distribution during embryogenesis. and can be found in adults in a variety of pathological conditions. In normal skin, tenascin is expressed at low levels, but it is upregulated in skin tumours, in a number of skin diseases with epidermal hyperproliferatkm and during wound healing. Several tenascin variants have been described, and these arise by alternative splicing. Using a monoclonal antibody recognizing all tenascin variants, and polyclonal antibodies specific for the large tenascin variants, we have investigated tenascin expression in bullous diseases such as epidermolysis bullosa, pemphigus, bullous pemphigoid and pemphigoid gestationis. By immunohistochemistry, we have found increased tenascin staining in ail patient skin samples, with a more pronounced tenascin expression in samples of autoimmune bullous diseases. The large tenascin variants seem to be major forms of tenascin occurring in healthy skin. In patients with blistering diseases, however, these large variants appear to represent a subpopulation of the induced tenascin accumulation. These findings suggest different functions for the tenascin variants in normal and diseased skin.     

Increased expression of tenascin C by keloids in vivo and in vitro

Tenascin C, undulin, collagen XIV and fibronectin are extracellular matrix glycoproteins with a partial DNA sequence homology. During embryogenesis, tenascin C is abundant in mesenchymal tissues but its distribution in human adult tissue is severely restricted. The levels of tenascin C expression are enhanced with skin inflammation, wound healing and hyperproliferative skin diseases and return to normal in normal scar tissue after wound contraction is completed. Undulin/collagen XIV is associated with collagen fibrils and fibronectin is present throughout the dermis in adult skin but it is produced by keloidal fibroblasts in an increased amount. In this study we investigated by immunohistochemistry the expression of the three extracellular matrix proteins in keloids and normal skin as well as in keloidal and normal fibroblasts in vitro. In keloids, increased tenascin C expression was observed especially in the reticular dermis associated with collagen fibrils sharply demarcating the limit of the lesion. In normal tissue, tenascin C was only expressed beneath the basal lamina and dermal-epidermal junction. Corresponding to the in vivo findings, tenascin C expression was increased in keloidal fibroblasts compared with normal fibroblasts in vitro (P < 0.003), whereas undulin/collagen XIV and fibronectin expression in keloids and keloidal fibroblasts was similar to that in normal tissue and normal fibroblasts, respectively. Therefore, tenascin C is a marker associated with keloids and we suggest that keloidal fibroblasts, once stimulated, continue to produce tenascin C independently from circulating factors.     

端粒酶逆转录酶在皮肤肿瘤原位表达水平的比较

目的　研究端粒酶在皮肤恶性肿瘤发病机制中的作用。方法　采用人端粒酶逆转录酶 (hTERT)cRNA探针与石蜡标本进行原位杂交的方法检测 3 0例皮肤基底细胞癌、15例皮肤鳞状细胞癌、19例脂溢性角化、14例正常皮肤中hTERTmRNA的表达水平 ,并进行比较。结果　hTERT阳性率基底细胞癌为 73 .3 5 %(2 2 /3 0 ) ,鳞状细胞癌为80 .0 0 %(12 /15 ) ,均明显高于脂溢性角化 3 6.84%(7/19)和正常皮肤 2 8.5 7%(4 /14 ) ,并具有统计学意义。结论　hTERT在恶性皮肤肿瘤中的阳性表达率明显高于良性肿瘤和正常皮肤 ,提示端粒酶在皮肤恶性肿瘤发病机制中起着重要作用。原位杂交检测hTERT表达水平的方法有可能成为鉴别皮肤良恶性肿瘤的辅助检查手段。     

Tenascin expression in actinic keratosis

BACKGROUND: Tenascin is an extracellular matrix protein frequently expressed around neoplastic and non-neoplastic lesions of the skin. Actinic keratoses (AKs) are intraepidermal neoplastic lesions of the sun-exposed skin. They are classified according to the extension of dysplasia in four stages; they also present different histological varieties. METHODS: We performed an immunohistochemical study using tenascin monoclonal antibody diluted 1 : 50 on 150 cases of AKs classified, respectively, in histotypes (38 hypertrophic, 18 atrophic, 21 bowenoid, 19 acantolytic, and 40 mixed) and in stages (27 stage I, 46 stage II, 42 stage III, and 35 stage IV; 14 in tumoral progression). RESULTS: Tenascin positivity was observed in all cases at the dermal level close to the epithelial lesion. The intensity of reaction increased from stage I to stage IV and, of course, also in tumoral progression. Its expression was not related to the histotypes. In very few cases, the atypical keratinocytes were positive. CONCLUSIONS: Tenascin expression in AKs is related to the stages of dysplasia. In fact, the immunostaining intensity corresponds to the degree of the dysplasia rather than the thickness of the involved epidermis. Tenascin plays a role in neoplastic progression working as an anti-adhesive factor.     

Investigation of the expression of the extracellular matrix glycoproteins tenascin and fibronectin during acne vulgaris

Summary Tenascin and fibronectin are extracellular matrix glycoproteins which can interact with cells and alter their capacity to adhere, migrate and proliferate. In contrast with fibronectin, tenascin has a restricted distribution in normal skin, but is induced during epidermal proliferation, and in wound healing. Because acne involves hyperproliferation of ductal keratinocytes, and rupture of the duct may occur during inflammation, the distribution of tenascin and fibronectin was investigated in acne lesions, and also in acne keloids. Biopsies obtained from patients a ending the acne clinics were cryostat-sectioned and stained with tenascin antiserum. The extent of tenascin staining in the dermis around the pilosebaceous unit was measured. Tenascin was continually expressed around normal control pilosebaceous ducts: it was maximal around the acroinfundibulum, extending 20·83±9·32 μm [ n = 14) into the dermis, compared with staining around the infrainfundibulum (11·88± 3·70 μm. N = 14). This was not significantly different from staining around normal pilosebaceous ducts obtained from acne patients. In non-inflamed lesions tenascin staining increased significantly around the infrainfundibulum to 76·88±29·97 μm ( n = 12), compared with this region in the normal follicles. The staining around the acroinfundibulum did not change significantly. Around inflamed lesions the whole of the dermis was positive for tenascin. No changes were detected in the staining pattern for fibronectin, which stained the whole dermis in all the sections tested. The keloid samples stained strongly for both extracellular matrix glycoproteins. Thus, increased tenascin expression appears to be associated with the development of acne lesions. Tenascin production may be induced by hyperproliferation of ductal keratinocytes and localized loss of control in this process may contribute to the production of acne keloids.     

Radiation therapy induces tenascin expression and angiogenesis in human skin.

In analysing radiation-induced connective tissue changes, we studied tenascin expression, elastic fibres, angiogenesis and physio-mechanical properties in irradiated and contralateral healthy skin of radiotherapy-treated breast cancer patients. Skin biopsies were obtained from a radiotherapy-treated skin area and a corresponding non-treated skin area. Haematoxylin-eosin and Verhoeff stainings as well as immunohistochemical stainings for tenascin and factor VIII were performed. Epidermal and total skin thickness, together with the amount of elastic tissue calculated by computerized digital image analysis, were measured. Suction blisters were induced on both skin areas. Transepidermal water loss was analysed. Skin elasticity was also measured. Tenascin expression was found to be increased in irradiated human skin. In haematoxylin-eosin and factor VIlI-stained sections, an increase in the number of blood vessels was detected. Although skin stiffness measured by an elastometer was increased in irradiated skin, no marked difference in the elastic fibres could be found between treated and non-treated skin. The increased tenascin expression could be due to activation of cytokines as a result of irradiation. An increase in angiogenesis could be caused by an activation of angiogenetic factors by irradiation or due to direct radiation damage on blood vessel walls. Our findings suggest that the effects of irradiation tend to accumulate in the dermal parts of skin. The higher skin stiffness values measured by elastometer in irradiated skin could be due to an accumulation of dermal connective tissue as a result of irradiation.     

Expression of tenascin, biglycan and decorin in disorders of keratinization

Summary The distribution of three (recently discovered) extracellular matrix components (tenascin, biglycan and decorin) was studied in normal adult human skin and in a number of monogenic disorders of keratinization, using immunohistology. The expression of tenascin, which is sparsely distributed in normal human dermis, was found to be grossly increased in epidermolytic hyperkeratoses and in Darier's disease. Tenascin expression in three types of ichthyosis (X-linked recessive ichthyosis. autosomal dominant ichthyosis vulgaris. non-erythrodermic lamellar ichthyosis) was similar to that of normal skin. The presence of biglycan and decorin did not show a marked variation between the different disorders studied, suggesting that their expression is subject to regulatory mechanisms distinct from those of tenascin.
The increased expression of tenascin in two disorders of keratinization with a hyperproliferative phenotype, lends further support to the hypothesis that dermal tenascin expression is increased as a result of epidermal hyperproliferation.     

Nodular Scleroderma: Focally Increased Tenascin Expression Differing from That in the Surrounding Scleroderma Skin

Nodular scleroderma is a rare variant of the disease, whose pathogenesis is uncertain. Tenascin is a recently cloned extracellular matrix protein which is thought to be a marker for tissue remodelling. To further investigate the pathogenesis of nodular scleroderma, we have followed up a case of this disease and studied tenascin expression in the nodular lesions and surrounding progressive systemic sclerosis skin. Previously, we demonstrated a long-lasting intermediate level of dermal tenascin expression in progressive systemic sclerosis; morphea and hypertrophic scar lesions showed strong but short-lived tenascin expression. In our current patient, high levels of tenascin were found in the nodules, which rapidly resolved. Thus, the time course of the clinical and histopathological findings together with the tenascin expression were more suggestive of hypertrophic scar than progressive systemic sclerosis. These findings imply that nodular scleroderma has a supplementary pathogenesis, such as itching, in addition to the proceeding systemic sclerosis.     

An Immunohistochemical Study of BCA-225 in Various Skin Cancers

We performed an immunohistochemical study of BCA-225, which is a glycoprotein secreted by the T47D breast carcinoma cell line and recognized by monoclonal antibody BRST-1 (clone name: CU-18), in normal skin and various skin cancers. In normal skin, BCA-225 was positive only in the secretory portion of both eccrine and apocrine glands and in mature cells of the sebaceous gland. We observed 10 cases of squamous cell carcinoma of the skin, 10 cases of basal cell carcinoma without sebaceous differentiation, 3 cases of basal cell carcinoma with sebaceous differentiation, 6 cases of malignant trichilemmoma, 8 cases of eccrine porocarcinoma, 3 cases of ductal carcinoma, 1 case of malignant clear cell hidradenoma, 1 case of apocrine adenocarcinoma, 6 cases of extra-ocular sebaceous carcinoma, 5 cases of extramammary Paget's disease with underlying adenocarcinoma, and 11 cases of extramammary Paget's disease without underlying adenocarcinoma. Most of the cases of sweat gland carcinoma, basal cell carcinoma with sebaceous differentiation, sebaceous carcinoma, and extramammary Paget's disease were positive for BCA-225, while none of the cases of squamous cell carcinoma, basal cell carcinoma without sebaceous differentiation, or malignant trichilemoma were positive. Based on these findings, we believe that BCA-225 is useful in distinguishing tumors with sweat gland and sebaceous differentiation and extramammary Paget's disease from tumors without such differentiation.     

Expression of glutathione S-transferase-pi in malignant skin tumors.

GST-pi has been known to be markedly increased in human (pre) neoplasms of several organs. In this paper, the significance of immunohistochemical detection of GST-pi in human malignant tumors of the skin was studied. In specimens from 40 patients with various skin cancers, malignant melanoma, Paget's disease and undifferentiated squamous cell carcinoma showed strong reactivity in GST-pi staining. The reactions were negative or weak in Bowen's disease, basal cell epithelioma and solar keratosis. In normal melanocytes, eccrine, apocrine, and breast gland cells stained positively but not in keratinocytes, sebaceus gland and fibroblasts. While immunohistochemical detection of GST-pi in the skin was not specific for malignancies, it contributed to aid the distinction of squamous cell carcinoma from other keratinocytic tumors. GST-pi might provide potentially useful information on chemosensitivity of skin cancer, and might serve as a biomarker of disease activity.     

CD44在某些皮肤肿瘤中表达的初步研究

目的：探讨CD44在皮肤肿瘤中的表达情况。方法：免疫组化法。结果：在鳞癌和基癌中,癌巢距表皮越近,CD44的表达越强;反之,CD44的表达越弱。在痣细胞痣和恶性黑素瘤（恶黑）标本中,CD44标准型（CD44S）均表达。在其它皮肤肿瘤中,CD44的表达同正常皮肤。结论：在鳞癌和基癌中,CD44的表达与癌巢距表皮的远近有关。CD44S的表达与痣细胞的良性或恶性无关。     

Electron microscopic microanalysis of prickle cell carcinoma, basaloma, malignant melanoma and normal skin

EMMA has been used in Dermatology since 10 years. In 1981, Fisher established the Cu/Zn index as a parameter for the prognosis of malignant melanoma. We tested the EMMA technique as a means to determine the Cu/Zn index in basal cell carcinoma, squamous cell carcinoma, malignant melanoma, and normal skin. Our preliminary conclusions are: EMMA may be useful to determine the Cu/Zn index in skin tumors; it is possible to obtain useful data from tumors already fixed in paraffin; (c) the highest Cu/Zn index was found in normal skin, the lowest one in malignant melanoma.     

水通道蛋白3在四种皮肤肿瘤中的表达

目的 探讨水通道蛋白3（AQP3）在四种皮肤肿瘤组织中的表达及意义。方法 应用免疫组织化学方法检测30例脂溢性角化病、15例Bowen病、32例鳞状细胞癌、17例恶性黑素瘤及15例正常人皮肤组织中AQP3的表达。结果 脂溢性角化病、Bowen病、鳞状细胞癌、恶性黑素瘤及正常人表皮组织中均存在AQP3蛋白的表达;脂溢性角化病皮损中AQP3表达水平与正常人对照组差异无统计学意义（P > 0.05）;Bowen病、鳞状细胞癌及恶性黑素瘤皮损中AQP3蛋白表达显著高于正常人对照组（P < 0.01）,其中鳞状细胞癌与恶性黑素瘤的表达最强,均显著高于Bowen病（P < 0.01）,但鳞状细胞癌与恶性黑素瘤比较差异无统计学意义（P > 0.05）。此外,在鳞状细胞癌中AQP3的表达与肿瘤的分化有显著相关性（P < 0.01）;在已转移恶性黑素瘤中AQP3的表达显著高于未转移恶性黑素瘤（P < 0.05）。结论 AQP3在皮肤恶性肿瘤中表达上调。     

CD44 Expression in Normal Human Skin and Skin Tumors

CD44 is thought to be a principal cell surface receptor for hyaluronic acid. Although the distribution of hyalulonic acid has been studied, little is known about the distribution of the CD44 molecule in the human skin and skin tumors. This study was undertaken to investigate the distribution of the CD44 molecule in normal human skin as well as in benign and malignant skin tumors. In normal skin, CD44 was expressed on 1) keratinocyte cell surfaces throughout the epidermis except for the granular and horny layers, 2) hair follicular cells, 3) eccrine sweat gland cells, and 4) cell surfaces of dendritic cells in the dermis. In skin tumors, although CD44 was expressed on the tumor cell surface of seborreic keratosis, Bowen's disease, and squamous cell carcinoma as in normal skin, we could not detect any CD44 expression on the cell surface of the tumor cells of basal cell carcinoma. However, CD44 positive dendritic cells were observed in the tumor islands of basal cell carcinoma. Phenotypic analysis suggested that these CD44 positive cells were melanocytes.     

Greater expression of TC21/R-ras2 in highly aggressive malignant skin cancer

Background TC21 plays an important role in highly aggressive tumor formation, and it was overexpressed in several human cancers, including breast cancer, oral squamous cell carcinoma (SCC), and esophageal SCC. In light of this, we explored the expression of TC21 in overall skin cancers in order to evaluate the relationship between TC21 and malignant skin tumors. Methods We examined six normal skin tissues and 18 malignant skin tumor tissues, including six malignant melanomas (MM), six SCCs, and six basal cell carcinomas (BCCs) using western blotting for the expression of TC21. In another set, 16 specimens of MM, 16 SCC, and 16 BCC were analyzed for the expression of TC21 using immunohistochemical staining. To evaluate the amount of expression of TC21, the Raytest TINA software was used for western blotting and a histochemical score (HSCORE) was used for immunohistochemical evaluation. Results The western blotting and immunohistochemistry showed that TC21 was expressed in all malignant skin tumors and not in normal skin tissues. The relative protein expression was an average of 0.004 in normal skin, 1.042 in MM, 0.621 in SCC, and 0.485 in BCC. In immunohistochemistry, HSCORE for normal skin was an average of 0.05, MM was 2.42, SCC was 2.11, and BCC was 1.22. Conclusions This article is the first study demonstrating expression of TC21 in human skin malignant tumors and suggests that TC21 is more expressed in highly aggressive skin tumors.     

Sozialrechtliche Bewertung UV-induzierter Hauttumoren

The present work deals with insurance and legal issues on the prevention of UV-induced skin tumors. We are convinced that squamous cell carcinoma of the skin fulfils the socio-legally required conditions according to paragraph 9 Abs. 2 SGB VII for approval as an occupational disease. In malignant melanoma evidence also exists for its induction through UV exposure and increased risk for occupational UV exposure, thus, making approval as an occupational disease possible in individual cases. According to the currently available medical knowledge on basal cell carcinoma and malignant melanoma, there is no sufficient basis for the approval of these as occupational disorders. Therefore, significant actions should not only be taken in the context of primary disease prevention, but also within the framework of secondary and tertiary disease prevention in occupational UV exposure.