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.     

Immunohistochemical analysis of antimelanoma monoclonal antibodies, with special reference to fetal tissue distribution

An immunohistochemical study using 2 antihuman melanoma monoclonal antibodies designated as MoAb 225.28S and MoAb 653.40S was carried out on various human skin tumors, including malignant melanoma as well as on normal and fetal tissues by indirect immunofluorescence technique. Specific immunofluorescence was observed not only in malignant melanoma cells but also in cells of pigmented nevi, basal cell epithelioma, normal hair follicles, and some fetal tissues. Both monoclonal antibodies were revealed to be able to recognize the common antigenic determinant shared by several skin tumors, including malignant melanoma, and fetal tissues. Therefore, both monoclonal antibodies might recognize premature antigen of both melanocytic and keratinocytic cell lineage.     

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。     

Expression of transferrin receptor in normal human skin, psoriatic skin and various skin tumors

The distribution of transferrin receptor in normal human skin and its expression in psoriatic skin and various skin tumors have been investigated. Immuno-peroxidase staining was performed on biopsy specimens using monoclonal OKT 9 antibody, which reacts with transferrin receptor. Normal human skin showed positive staining with OKT 9 in eccrine glands and outer root sheaths of the hair. Sebaceous glands were also strongly positive. The basal layer stained very weakly. Psoriatic skin expressed OKT 9 strongly in the epidermis, especially in the area of the rete ridge. In squamous cell carcinoma, Bowen's disease, and malignant melanoma, a widespread and strong labelling reaction was found. Basal cell epithelioma and genital Paget's disease were partially and moderately positive in their staining pattern. No such positive staining pattern could be found in either nevus cell nevi or seborrhoic keratosis. These findings indicate that, in normal skin, transferrin receptor exists in eccrine glands, sebaceous glands, and outer root sheaths of the hair in greater amounts. High amounts of expression of this receptor in psoriatic epidermis and malignant tumors suggests that immunohistochemical demonstration of transferrin receptor parallels the proliferating activity of the tissue or tumor of the skin and may provide an useful aid for detecting such conditions.     

Detection of epidermal growth factor-like factors in various skin tumors

EGF-like factors (EGF-F) in tissue extracts make use of the EGF receptor system (EGF-R) in order to transmit biological signals. EGF-F, which partly show transforming activities, can be detected with the help of an EGF receptor assay. We measured the EGF concentrations in extracts of 25 benign, 5 semi-malignant, and 13 malignant skin tumors, as well as in 5 biopsies of normal skin. The highest amounts of EGF-F were found in malignant melanoma (10 ng/mg) and in squamous cell carcinoma (7 ng/mg). The EGF-F concentrations in benign and semi-malignant tumors, in contrast, were similar to those found in normal skin (up to 4 ng/mg). Isoelectric focusing (IEF) revealed that the activity of EGF-F malignant tumors consists of various components.     

Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell carcinoma and 174 matched controls, and 168 cases with cutaneous malignant melanoma and 176 matched controls. Controls were matched on age, gender and place of residence. Subjects indicated their hair colour before 7 years of age, and at 25 years of age and their skin phototype. Interviewers assessed the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair colour and skin type were found to be independent risk factors for cutaneous malignant melanoma; red hair vs. black/brown: OR >9.7, blond hair vs. brown/black: OR = 2.4, and skin type 11 vs. type IV: OR=2.0. There were no gender-related differences in risk factors for basal cell carcinoma and cutaneous malignant melanoma.     

Multicellular origin of tenascin in skin tumors – an in situ hybridization study

Tenascin mRNA expression was studied by an in situ hybridization method in 27 skin tumors. Tenascin synthesis was increased in all skin tumors when compared to uninvolved skin but there was variation in the site of cellular synthesis between different types of tumors. In melanocytic nevi and precancerous keratinocyte lesions, tenascin seemed to be of epidermal or stromal origin. In basal cell carcinoma, squamous cell carcinoma and malignant melanoma, there was tenascin synthesis also in tumor cells. These findings are in concordance with earlier studies which suggest a role of tenascin as an anti-adhesive and motility-promoting factor in malignant skin tumors.     

Pattern of skin cancer among Saudi patients attending a tertiary care center in Dhahran,Eastern Province of Saudi Arabia. A 20‐year retrospective study

Skin cancer is the ninth most common malignancy in Saudi Arabia. It represented 3.2% of all newly diagnosed cancer cases in the year 2010. The aim of this study was to determine the epidemiology of skin cancer in relation to age, sex, and anatomic location among Saudi patients attending the Johns Hopkins Aramco Healthcare center in Dhahran, Eastern province of Saudi Arabia. We retrospectively reviewed the surgical pathology records of Saudi nationals from 1995 to 2014 at the Johns Hopkins Aramco Healthcare center, which directly provides for the healthcare needs of Saudi Aramco company employees and dependents in the Eastern Province of Saudi Arabia. Tumor metastases to skin, skin involvement by primary breast carcinoma, and B‐cell leukemia/lymphoma with secondary involvement by skin were excluded. The total number of primary skin tumors was 204. The commonest cutaneous malignancies were basal cell carcinoma (36%) followed by squamous cell carcinoma (23%), with the head and neck being the commonest location for both tumors. Mycosis fungoides (MF) was the third most common malignancy (11%). Malignant melanoma was the fourth commonest skin malignancy (7%) with the lower extremities being the commonest location. The four most common skin cancers in our tertiary center in the Eastern Province of Saudi Arabia were squamous cell carcinoma, basal cell carcinoma, MF, and malignant melanoma. Other regions of Saudi Arabia report a similar pattern of skin cancers as our center, with MF having a higher frequency at our center.     

HMB-45 recognizes stimulated melanocytes

A monoclonal antibody (HMB-45) was previously reported to bind to melanoma cells, and the junctional component of nevus cells, but not to normal adult melanocytes. We have tested HMB-45 binding in several conditions under which melanocyte stimulation might be expected in adults, i.e. 3 simple lentigines, 2 solar lentigines, 7 recent surgical scars (from re-excision of non-melanocytic tumors), 2 surgical scars from re-excisions of melanomas (after complete primary excisions), 9 hemangiomas from non-sun-exposed skin, 1 basal cell carcinoma, 1 acute ecchymosis, 1 keloid, and 1 dermatofibroma. Positive controls included 6 malignant melanomas and 1 fetal skin sample. Melanocytes were strongly positively stained overlying hemangiomas, within or near recent surgical scars of melanocytic and non-melanocytic tumor re-excisions, near basal cell carcinoma, and in fetal skin. Melanocytes either were not stained or were stained only focally for trace amounts in the normal skin near the new margins of the wide re-excision specimens for melanoma, i.e., at a distance from the scar, in the simple lentigines and in the fibrotic lesions. Thus, HMB-45 is staining an antigen which appears in adult melanocytes during stimulation and in fetal skin, as well as in melanomas. This stimulation is associated with conditions that would have increased vascularity, suggesting a melanocyte response to a plasma factor, or other endothelial cell derived factor. HMB-45 would not be a useful marker for residual melanoma cells in melanoma re-excision specimens.     

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。     

炎性小体在皮肤肿瘤中的研究进展

【摘要】 炎性小体是一种细胞内多蛋白复合物,是固有免疫应答的组成部分。炎性小体的功能异常可以导致机体免疫失衡,并与许多疾病密切相关。研究表明,炎性小体与基底细胞癌、鳞状细胞癌、Kaposi肉瘤及恶性黑素瘤等皮肤肿瘤有一定相关性,提示炎性小体异常活化造成的持续炎症反应及免疫应答失衡是皮肤肿瘤发生、发展、侵袭及转移的重要环节。本文概述炎性小体在皮肤肿瘤发病机理中的研究进展。     

Tubulin expression in melanocytic skin tumors. An immunohistochemical study

The microtubulus system as a part of the cellular cytoskeleton contributes to cell movement. Microtubulus assembly and disassembly is considered to be essential for tumor invasion and serves as a target for tumor chemotherapy. Using immunohistochemical methods, we investigated the distribution of tubulin in normal skin and 34 melanocytic skin tumors. In normal skin, tubulin was strongly expressed in dermal nerves, melanocytes, fibroblasts within the papillary dermis and in myoepithelial cells. In melanocytic skin tumors, nevus cells and melanoma cells stained positive, particularly at the periphery of the lesions, where there were single cells and small nests. The main difference between benign and malignant melanocytic tumors was found in the stromal cells: In melanocytic nevi, the stromal fibroblasts were entirely tubulin negative; whereas, adjacent to the invasive edge in primary and metastatic malignant melanoma, the stroma fibroblasts were strongly positive. Our results show that tubulin is regularly expressed in melanocytic skin tumors and may serve as a prerequisite for cell movement. The pronounced expression of tubulin in fibroblasts surrounding malignant melanocytic skin lesions reflects a stromal alteration that might contribute to tumor invasion.     

Melanocytes express 3G5 surface antigen

The 3G5-reactive ganglioside antigen (3G5 antigen) is expressed on the surface of various cell types including pericytes, pancreatic islet cells, thyroid follicular cells, and cells of the pituitary and the adrenal medulla. Expression on melanocytes has not yet been reported. We examined 148 5-microm cryosections of 12 normal skin samples and 45 skin tumors (21 melanocytic nevi, 8 malignant melanoma primaries, 4 metastases of malignant melanoma, 3 basal cell carcinomas, and 9 pigmented seborrheic keratoses) by triple fluorescence technique with the monoclonal antibody 3G5, DNA fluorochrome, and the anti-melanocytic antibody A103 (Anti-Melan-A). In normal skin, 3G5 reactivity was detected in epidermal melanocytes of 4 of 12 cases with 14.8 +/- 24.1% positive melanocytes; 20 of 21 nevi (72.2 +/- 29.1% positive nevus cells, mean +/- SD), 8 of 8 primary melanomas (83.9 +/- 12.3% positive melanoma cells), and 4 of 4 melanoma metastases (82.5 +/- 6.5% positive melanoma cells) expressed the 3G5 antigen. All tumor cells of investigated basal cell carcinoma or seborrheic keratosis were 3G5 negative. This is the first report of 3G5 antigen expression in melanocytes. The data demonstrate high expression of this ganglioside in the aggregated melanocytes of malignant or benign tumors but low or absent expression in singular melanocytes (normal epidermis, seborrheic keratoses) reflecting a different biologic state.     

Electron microscopic examination of cutaneous lesions by the quick re-embedding method from paraffin-embedded blocks

We attempted to evaluate whether Widéhn's quick re-embedding method from paraffin blocks is useful for dermatopathological diagnosis. Regarding fine preservation of nuclei, tonofibrils and desmosomes of keratinocytes in normal skin, we could recognize no difference between the quick re-embedding method and traditional re-embedding methods. However, preservation of mitochondria and Birbeck granules in Langerhans cells was poor regardless of the method used. Furthermore, we studied the ultrastructural features of some viral skin diseases including mollscum contagiosnm, herpes simplex, varicella-zoster and verruca vulgaris, and some skin tumors, including angioleiomyoma, angiosarcoma, Merkel cell carcinoma and amelanotic melanoma using the quick re-embedding method. We determined that all viral structures were sufficiently preserved by the quick method to observe the virions and developement of the virus. Myolilaments and dense bodies of angioleiomyoma, Wcibel-Palacle bodies of angiosarcoma, neurosecretory granules of Merkel cell carcinoma and melanosomes of amelanotic melanoma were recognized by the quick method. From these results, we concluded that the quick re-embedding method is useful for the diagnosis of skin diseases, especially viral skin diseases and some skin tumors.     

Dermatologische Radiotherapie

Dermatologic radiotherapy is based on the standard physical and radiobiological parameters. The radiation quality most often used in dermatology lies between 10 and 50 kV. Another important parameter is the half-value depth which should correspond to the depth of the tumor below the skin surface. In this way the skin is not over-exposed to radiation treatment. Indications for radiotherapy of malignant skin tumors include basal cell carcinoma, squamous cell carcinoma, severe actinic keratoses, lentigo maligna, lentigo maligna melanoma, Merkel cell carcinoma, and Kaposi sarcoma, as well as T- and B-cell lymphomas. Most patients with malignant skin tumors require life-long monitoring after radiotherapy. The most common benign lesions where radiotherapy may be indicated are eczemas, psoriasis, and keloids, but its use should be carefully weighed in these settings.     

MEL4B3, a novel mRNA is induced in skin tumors and regulated by TGF-beta and pro-inflammatory cytokines

Tumor-stroma interactions play a decisive role in the growth and metastasis of solid tumors, and involve signalling either by soluble mediators or direct cell-cell interaction. Here, we report the isolation and characterisation of a novel cDNA (MEL4B3), which is induced in cultured dermal fibroblasts exposed to supernatants of melanoma cell lines. MEL4B3 shares high homology with two predicted cDNA sequences for which no activity has so far been described. In situ hybridisation revealed the expression of MEL4B3 in malignant melanoma increasing with tumor depth; in basal cell carcinoma and in squamous cell carcinoma. MEL4B3 was barely detectable in normal skin or non-malignant melanocytic naevi. Furthermore, MEL4B3 was expressed at high level in the epidermis of psoriatic skin. In vitro, the expression of MEL4B3 was found to be induced by the exposure of human dermal fibroblasts to melanoma cell culture supernatants or to transforming growth factor-beta, interleukin-1 and tumor necrosis factor-alpha. The expression MEL4B3 therefore reflects closely cell activation occurring during tumor growth, metastasis and inflammation.     

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.     

Dermatologic radiotherapy

Dermatologic radiotherapy is based on the standard physical and radiobiological parameters. The radiation quality most often used in dermatology lies between 10 and 50 kV. Another important parameter is the half-value depth which should correspond to the depth of the tumor below the skin surface. In this way the skin is not over-exposed to radiation treatment. Indications for radiotherapy of malignant skin tumors include basal cell carcinoma, squamous cell carcinoma, severe actinic keratoses, lentigo maligna, lentigo maligna melanoma, Merkel cell carcinoma, and Kaposi sarcoma, as well as T- and B-cell lymphomas. Most patients with malignant skin tumors require life-long monitoring after radiotherapy. The most common benign lesions where radiotherapy may be indicated are eczemas, psoriasis, and keloids, but its use should be carefully weighed in these settings.     

The influence of painful sunburns and lifetime sun exposure on the risk of actinic keratoses,seborrheic warts,melanocytic nevi,atypical nevi,and skin cancer

Painful sunburns are implicated in the pathogenesis of squamous cell carcinoma, basal cell carcinoma, and malignant melanoma. Chronic exposure to ultraviolet radiation is known as the most important risk factor for the development of actinic keratoses and squamous cell carcinoma. The purpose of the study was to assess the effect of painful sunburns and lifetime sun exposure on the development of actinic keratoses and seborrheic warts in relation to the development of squamous cell carcinoma and basal cell carcinoma, and on the development of melanocytic nevi and atypical nevi in relation to the development of malignant melanoma. We made use of a cohort of 966 individuals who participated in a case-control study to investigate environmental and genetic risk factors for skin cancer. Exposure measurements for sunlight were collected and actinic keratoses, seborrheic warts, melanocytic nevi, and atypical nevi were counted. Relative risks were estimated using exposure odds ratios from cross-tabulation. Multivariate logistic regression was used to adjust for potential confounders. The recall of painful sunburns before the age of 20 y was associated with an increased risk of squamous cell carcinoma, nodular basal cell carcinoma, and multifocal superficial basal cell carcinoma as well as actinic keratoses. Odds ratios with 95% confidence intervals adjusted for age, sex, and skin type were 1.5 (0.97; 2.3); 1.6 (1.1; 2.2); 2.6 (1.7; 3.8); and 1.9 (1.4; 2.6) for the three types of nonmelanoma skin cancer and actinic keratoses, respectively. Painful sunburns before the age of 20 y were also associated with an increased risk of malignant melanoma and the development of its precursors, melanocytic nevi and atypical nevi. Odds ratios with 95% confidence intervals adjusted for age, sex, and skin type were 1.4 (0.86; 2.1); 1.5 (1.1; 2.0); and 1.4 (0.88; 2.3) for malignant melanoma and the two types of precursors, respectively. Lifetime sun exposure was predominantly associated with an increased risk of squamous cell carcinoma (p-value for trend=0.03) and actinic keratoses (p-value for trend <0.0001) and to a lesser degree with the two types of basal cell carcinoma. By contrast, lifetime sun exposure appeared to be associated with a lower risk of malignant melanoma, despite the fact that lifetime sun exposure did not diminish the number of melanocytic nevi or atypical nevi. Neither painful sunburns nor lifetime sun exposure were associated with an increased risk of seborrheic warts.