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.     

Expression of cytoskeletal components in melanocytic skin lesions. An immunohistochemical study

The cytoskeleton is considered to be important for maintaining cell shape and facilitating cell movement. In the present study, the expression of cytoskeletal components is examined in benign and malignant melanocytic skin tumors. Paraffin sections of 75 cases (25 each of nevocellular nevus, primary malignant melanoma, and cutaneous metastases of malignant melanoma) were stained with antibodies to tubulin, myosin, actin, and vimentin using a three-step immunoperoxidase method. The staining results were assessed independently for tumor cells and stroma cells in comparison to inbuilt reference structures. Vimentin is found in all melanocytic lesions in the tumor as well as in the stroma cells. In malignant lesions, the tumor cell staining intensity varies between neighboring regions; particularly in malignant melanoma the staining is pronounced in the tumor periphery (chi 2 test: p less than 0.05). Actin is only weakly positive in nevus cells and primary melanoma tumor cells, but strongly expressed in metastatic tumor cells (p less than 0.001). Nevus fibroblasts are only weakly positive, whereas the stroma fibroblasts in the malignant lesions are strongly positive (p less than 0.001). The same is true for myosin and tubulin expression in dermal fibroblasts (p less than 0.001), whereas the tumor cells are equally (weakly) positive in all melanocytic lesions. Our study shows that there are significant differences in the immunohistochemical expression of cytoskeletal components in various melanocytic tumors. There is an elevated expression of vimentin and actin in the tumor cells, particularly of metastatic lesions. However, the most pronounced differences are found in the dermal fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)     

CYLD基因与皮肤附属器肿瘤的研究进展

圆柱瘤、毛发上皮瘤、Brooke-Spiegler综合征均是临床少见的呈常染色体显性遗传的皮肤附属器肿瘤,其发生与CYLD基因突变密切相关。CYLD是一种肿瘤抑制基因,编码去泛索化蛋白酶,通过去泛素化核因子κB抑制蛋白激酶复合体的调节亚基、肿瘤坏死因子受体相关因子等信号分子负性调节核因子-κB途径,从而抑制肿瘤的发生。概述CYLD基因与皮肤附属器肿瘤的发生、基因型与表型的关系、皮肤肿瘤的治疗新进展。     

Mixed tumors of the skin. A histological and immunohistochemical study

Sixty-four specimens of mixed tumors of the skin were studied by conventional microscopy. Sections from all 64 specimens were stained by hematoxylin and eosin, and sections from 18 of those specimens were stained by immunoperoxidase techniques for the presence of S-100 protein, carcino-embryonic antigen (CEA), keratin, actin, vimentin, epithelial membrane antigen (EMA), and gross cystic disease fluid protein-15 (GCDFP-15). Two distinctive histopathological patterns of mixed tumors of the skin became apparent, namely, apocrine and eccrine. Mixed tumors with apocrine features are by far the most common. Immunoperoxidase techniques, in our experience, do not enable differentiation between apocrine and eccrine types of mixed tumors.     

An immunohistochemical study of mixed tumor of the skin.

An asymptomatic tumor developed on the upper lip of a 63-year-old man. Histologically, the tumor contained glandular and cystic structures forming many branching lumina, and many scattered single cells in an abundant mucoid to chondroid stroma. The tumor was diagnosed as mixed tumor of the skin. Histochemically, the cells composing the tubular structures contained neutral mucopolysaccharides and the stroma, acid mucopolysaccharides. Immunohistochemically, the cells of the glandular and cystic structures showed epithelial and sweat gland differentiation (EMA-, CEA-, BRST-1- and BRST-2-positive), while the cells scattered in the stroma showed a tendency toward myoepithelial differentiation (S-100 protein- and vimentin-positive).     

Expression of PGP 9.5 in granular cell nerve sheath tumors: an immunohistochemical study of six cases

BACKGROUND: Protein gene product 9.5 (PGP 9.5) is expressed in brain at 20 to 50 times the levels detected in other organs. Immunohistochemical studies reveal this protein is localized to both central and peripheral neurons. Recently, PGP 9.5 is reported to be a useful marker for cellular neurothekeomas. Herein we test whether PGP 9.5 is a new marker for granular cell nerve sheath tumors. MATERIAL AND METHODS: An immunohistochemical analysis for PGP 9.5 expression was carried out on all cases with the diagnosis of granular cell nerve sheath tumor seen over a 2-year period. In addition, we compared expression of PGP 9.5 with other accepted markers for neuroectodermal tumors including anti-S-100 protein and NKI/C3 monoclonal antibodies. RESULTS: Six granular cell nerve sheath tumors were diagnosed in over 80,000 dermatopathology specimens in the two-year period. These cases were all positive for PGP 9.5 as well as for S-100 protein and NK1/C3. CONCLUSION: These findings identify PGP 9.5 as a new immunohistochemical marker for use in the diagnosis of granular cell tumors. They also strengthen the histogenetic relationship between granular cell nerve sheath tumors and tumors of Schwann cell or perineurial origin.     

Expression of serotonergic receptors in psoriatic skin

Psoriasis appears to be influenced by stress, which causes release of adrenal hormones. Serotonin, or hormonal actions on serotonin and serotonin receptors, may have a role in psoriasis. Distribution of serotonin receptors was studied in involved and noninvolved skin in patients with psoriasis and compared to normal skin, by using immunohistochemistry and antibodies to 5-HT1A, 5-HT2A and 5-HT3 receptors (R). There was a decreased (P<0.001) number of 5-HT1AR positive cells, the majority being tryptase positive, in involved and noninvolved psoriatic papillary dermis, compared to normal skin. 5-HTlAR expression was also found in the upper part of the epidermis, on vessel walls and on melanocytes. 5-HT2AR expressing papillary mononuclear cells, CD3 positive, were increased (P<0.001 and P<0.01, respectively) in involved and noninvolved psoriatic skin, compared to normal skin, an increase (P<0.01) also being found in the involved compared to noninvolved skin. Expression of 5-HT3R could be found in the basal epidermal layer of noninvolved but not in the involved skin of psoriasis, where it was only found in the acrosyringium. The present findings are compatible with the 5-HT1A and 5-HT2A receptors having antagonistic functions, and raise the possibility of using receptor specific drugs in the treatment of psoriasis.     

Epidermal growth factor receptors in different skin tumors

Specific binding of 125I-labeled epidermal growth factor (EGF) was measured in 62 skin tumors of different severity. Within a group of 28 benign tumors, 11 of 15 condylomata acuminata were receptor positive, whereas the investigated mesenchymal tumors and normal skin as a control were receptor negative. 6 of 18 basal cell epitheliomas bound EGF specifically. In the group of precancerous and malignant skin tumors, 7 of 8 squamous cell carcinomas had the highest number of EGF binding sites and a high affinity state, whereas 5 malignant melanomas were receptor negative. The clinical relevance of these findings is not yet clear due to the short follow-up of the patients.     

Granuloma annulare: An immunohistochemical study

The monocyte/histiocytic response in granuloma annulare has not been extensively studied. We studied the immunohistochemical staining pattern in granuloma annulare by using a panel of markers for "histiocytic" cells including Ham 56, KP1, factor XIIIa, Mac 387, vimentin, and lysozyme. The infiltrate failed to stain with the histiocytic markers, except with antibodies against vimentin and lysozyme. Commonly used histiocytic markers for infectious, immunogenic, and foreign body granulomas fail to stain the infiltrate in granuloma annulare. We hypothesize that a locally derived, immunologically distinct population of histiocytes produces the reaction pattern of granuloma annulare.     

生存素和端粒酶逆转录酶在皮肤肿瘤中的表达

目的 研究皮肤肿瘤凋亡抑制基因生存素与人端粒酶逆转录酶(hTERT)的表达及相互关系.方法 免疫组化SP法检测17例鳞状细胞癌(鳞癌)、21例基底细胞癌(基癌)、19例鲍恩病、25例脂溢性角化病和13例正常人皮肤组织中生存素表达水平;原位杂交法检测上述组织中hTERT mRNA的表达水平;分析皮肤肿瘤中生存素与hTERT mRNA表达的相关性.结果 ①在鳞癌、基癌、鲍恩病中生存素及hTERT mRNA表达的阳性率均较正常人皮肤中显著增加;②脂溢性角化病中生存素表达的阳性率与正常人皮肤组织中比较差异有统计学意义,但hTERT mRNA表达的阳性率与正常人皮肤组织中比较差异无统计学意义;③鳞癌、基癌、鲍恩病中生存素阳性率及hTERT mRNA阳性率之间均呈显著正相关,脂溢性角化病中两者阳性率之间无显著相关性.结论 生存素与皮肤肿瘤发病关系密切,在鳞癌、基癌、鲍恩病中生存素与hTERT mRNA的表达具有一定的相关性.     

Elastic fibres in normal and sun-damaged skin: an immunohistochemical study

Sun-exposed and sun-protected skin obtained at post mortem from the nape of the neck in 14 subjects was immunostained using antisera to elastin, lysozyme, amyloid P component, and the plasma protease inhibitors alpha-I antitrypsin, alpha-I antichymotrypsin and alpha-2 macroglobulin. Both the normal elastic fibres in sun-protected skin, and elastosis in sun-exposed skin were positively immunostained for elastin, lysozyme and amyloid P component. Collagen fibres were unstained. No immunostaining of normal elastic fibres or elastosis in the skin was obtained with antisera to alpha-I antitrypsin, alpha-I antichymotrypsin or alpha-2 macroglobulin. It was concluded that the elastosis in sun-exposed skin does contain elastic fibres. The absence of immunostaining for plasma protease inhibitors probably indicates that the elastic material is mature, and not newly-formed.     

Hormonal interaction of androgen and estrogen receptors in normal skin and in acne

Hormone metabolism in skin affected with acne has been investigated by determination of androgen and estrogen receptors with the help of saturation analysis. The results have been compared with data of an age-corresponding control group. The investigation has been performed on 55 male and 11 female volunteers with acne in their lesions as well as unaffected areas. Androgen and estrogen serum levels have been determined as additional endocrine parameters. Testosterone serum levels were slightly elevated in about 11 percent of the male patients, while the percentage for the female patients might be higher as far as can be judged on account of small number of patients. The lack of correlation between estrogen/androgen receptors and their corresponding serum levels leads to the conclusion that the hormone metabolism is situated in the periphery, being independent of the central endocrine regulation. Similar findings for distribution and receptor levels in both healthy and involved skin of acne patients revealed a significant discrepancy in comparison to corresponding evaluations found in healthy patients. There results point out to an elevated dependency on hormonal influences of the entire integument of acne patients. Estrogen receptors could be found in both acne patients and controls.     

Basement membrane laminin and type IV collagen in various benign and malignant adnexal tumors of the skin: an immunohistochemical study

Thirty benign and seven malignant adnexal tumors of the skin and one lymph node metastasis were stained for laminin and type IV collagen with rabbit antibodies against the human basement membrane (BM) proteins using the immunoperoxidase technique. Fifteen of the benign sweat gland, sebaceous gland, and hair follicle tumors showed a continuous and distinct BM around the tumor aggregates. The cylindromas and eccrine spiradenomas seemed to produce excessive amounts of BM material, part of which was seen as amorphic patches within the tumor cell clusters, whereas the trichofolliculomas, trichoepitheliomas, and pilomatrixomas showed an absence of BM from many areas. In syringomas, in addition to the tubular structures surrounded by a continuous BM, undifferentiated cell nests containing granular BM material were present. They probably represent primitive structures obtaining during early development into tubules. The seven malignant tumors and the only metastasis studied here all contained small, narrow strips of BM material extracellularly between the infiltrating tumor clusters. Only in two cases was faint staining for laminin found within the cells. The pepsin pretreatment of the formalin-fixed, paraffin-embedded samples had most probably degraded the intracytoplasmic BM material in most cases. The BM defects were found to be associated with malignancy and low differentiation of the adnexal skin tumors, as reported previously for other tumor types, but a partial loss of BM was also associated with high differentiation in some benign adnexal tumors.     

Vascular structures in skin tumors: a dermoscopy study

OBJECTIVES: To describe the different vascular structures seen by dermoscopy and to evaluate their association with various melanocytic and nonmelanocytic skin tumors in a large series of cases. DESIGN: Digital dermoscopic images of the lesions were evaluated for the presence of various morphologic types of vessels. SETTING: Specialized university clinic. PATIENTS: From a larger database, 531 excised lesions (from 517 patients) dermoscopically showing any type of vascular structures were included. MAIN OUTCOME MEASURES: The frequency and positive predictive value of the different vascular structures seen in various tumors were calculated, and the differences were evaluated by the chi2 or Fisher exact test. RESULTS: Arborizing vessels were seen in 82.1% of basal cell carcinomas, with a 94.1% positive predictive value (P<.001). Dotted vessels were generally predictive for a melanocytic lesion (90.0%, P<.001), and were especially seen in Spitz nevi (77.8% of lesions). In melanoma, linear-irregular, dotted, and polymorphous/atypical vessels were the most frequent vascular structures, whereas milky-red globules/areas were the most predictive ones (77.8%, P = .003). The presence of erythema was most predictive for Clark nevus, whereas comma, glomerular, crown, and hairpin vessels were significantly associated with dermal/congenital nevi, Bowen disease, sebaceous hyperplasia, and seborrheic keratosis, respectively (P<.001 for all). CONCLUSIONS: Different morphologic types of vessels are associated with different melanocytic or nonmelanocytic skin tumors. Therefore, the recognition of distinctive vascular structures may be helpful for diagnostic purposes, especially when the classic pigmented dermoscopic structures are lacking.