HLA and β2-microglobulin Expression in Basal and Squamous Cell Carcinomas of the Skin

Histologic sections of seven squamous cell carcinomas (SCC), 13 basal cell carcinomas (BCC), and a Bowenoid actinic keratoses were examined for expression of HLA class 1 antigens (HLA-ABC) using a monoclonal antibody and an immunoperoxidase technique. Expression of beta 2-microglobulin was examined with a polyclonal antibody method. Neither cell marker was detected within the Bowenoid actinic keratoses. Squamous cell carcinomas and basal cell carcinomas exhibited decreased expression of both HLA-ABC and beta 2-microglobulin and often did not express these antigens at all. HLA-ABC was present in only two of 13 basal cell carcinomas and four of seven squamous cell carcinomas. beta 2-microglobulin was present in one of 13 basal cell carcinomas and two of seven squamous cell carcinomas. When present, these antigens often were present in a few areas of the tumor, but absent in others. In both SCC and BCC, both antigens were usually lost simultaneously. In all tumors with beta 2-microglobulin, HLA-ABC also was retained. There was no apparent relationship of anatomic site or type of tumor with retention of surface antigens. Since some tumors or portions of tumors retained HLA-ABC and beta 2-microglobulin on their surfaces, the absence of these antigens is not an absolute marker for malignancy.     

Serum β2-microglobulin levels in psoriatic patients

β₂-Microglobulin (β₂-M) is a low molecular weight protein forming the light chain of the class I major histocompatibility complex. It is found on the cell surface of all nucleated cells. Its serum concentration is found to be increased in kidney diseases, neoplasia, AIDS, chronic inflammation and autoimmune diseases. Inflammation plays an important role in the pathogenesis of psoriasis, especially psoriatic arthritis and immunological upset is one of the most implicated factors in the etiology of the disease. In this study, the sera β₂-M levels were evaluated in cases diagnosed as psoriasis vulgaris and psoriatic arthritis, and a statistically significant increase was found in cases of psoriatic arthritis compared to those of psoriasis vulgaris and the control group.     

β2-integrins in different forms of urticaria

As urticarial lesions involve tissue invasion by inflammatory cells, and as β₂-integrins play a central part in adhesion of leucocytes to endothelia, allowing their migration into the tissues, we have explored the distribution and sequential expression of these molecules in tissue sections from different forms of urticaria. Prick test weals (of 10 min duration) to common inhalant allergens showed only a minor increase of CD18, whereas in a case of cold urticaria CD11b and CD18 molecules were increasingly upregulated within the first 30 min after elicitation of the lesions. Skin test sites in delayed pressure urticaria, and urticarial esions (> 6 h duration) of acute and chronic recurrent urticaria also showed marked upregulation of CD11b and CD18, and to a lesser extent of CD11a, but this did not strongly correlate with the intensity of the mixed cellular infiltrate. Non-lesional skin showed expression of β₂-integrins in chronic urticaria, delayed pressure urticaria, and less so in acute urticaria, suggesting generalized leucocyte activation. This analysis of integrins thus suggests an early and extensive involvement of these molecules in the pathological events associated with the evolution of urticarial lesions.     

Decreased expression of α2β1 integrin in scleroderma fibroblasts

Abstract Systemic scleroderma (SSc) is a complex connective tissue disorder of unknown etiology. In early stages of the disease, libroblasts are activated to produce large amounts of collagen with subsequent fibrosis. Collagen metabolism of fibroblasts is modulated by their contact with the extracellular matrix (ECM), which involves distinct receptors on the cell surface, mainly belonging to the integrins. We investigated the expression of collagen receptor α₂β₁, in SSc and normal fibroblasts, since this receptor has been shown to be utilized by fibroblasts for adhesion to and reorganization of collagen I. 9 strains of scleroderma fibroblasts grown as monolayer cultures were first analyzed with respect to their collagen I expression. 6 of these strains were similar to controls (“low” producers) and 3 strains showed up to 2–3 × higher levels of collagen I mRNA expression (“high” producers). Northern hybridization using a cDNA probe specific for the α₂ integrin subunit revealed a decrease of the corresponding mRNA in SSc fibroblasts as compared to controls (75% versus 100%). “High” collagen producing cell strains displayed the lowest values for α₂ integrin mRNA. The decrease of α₂ integrin subunit expression at the mRNA level in selected fibroblasts was further substantiated by radioimmunoprecipitation using specific mAbs directed against α₂ integrin subunit. No significant changes in β₁ integrin expression could be observed-neither at mRNA nor at the protein level. Our data indicate a correlation between excessive synthesis of collagen and low levels of α₂ integrin subunit expression in SSc fibroblasts. Further experiments should clarify whether this observation is a phenomenon specific for scleroderma or whether it reflects an “activated” state of fibroblasts.     

The discriminatory diagnostic ability of β2-microglobulin labelling in viral warts, pseudoepitheliomatous hyperplasia and verrucous carcinoma of the skin

The value of β₂-microglobulin (B2M) labelling in discriminating between histologically similar benign and malignant lesions of the skin was assessed. It could distinguish pseudoepitheliomatous hyperplasia from verrucous carcinoma and frequently from viral warts, but could not reliably discriminate between verrucous carcinoma and viral warts. The qualitative loss of B2M seen in verrucous carcinoma and viral warts may partly be responsible for diminished immunological surveillance and hence for their clinical behaviour.     

β2 Microglobulin expression in keratoacanthomas and squamous cell carcinoma

The cell surface expression of beta-2-microglobulin (beta 2 M) was investigated in 33 keratoacanthomas (KA) and 58 squamous cell carcinomas (SCC) to determine whether this antigen was expressed to a different extent in these two conditions and, thus, whether this constitutes a reliable and practical test for distinguishing them. Loss of beta 2 M expression was not a reliable feature for distinguishing between KA and SCC and seemed to be related more to the degree of cellular differentiation and maturation, than to malignancy as such.     

α1-Antitrypsin Deficiency and Skin Abnormalities

A 19-year-old Moroccan male was found to have total absence of serum alpha₁-antitrypsin, a major inhibitor of elastase. This patient had chronic obstructive lung disease, hyperextensibility of the skin over the cheeks and wrists, and hyperlaxity of the hand joints. Microscopic sections of the skin revealed a thickened dermis with shortened and rarefied clastic fibers. Ultrastructural study showed collagen fibers with variable and irregular diameters. Elastic fibers were scarce and their relatively poor matrix was surrounded by numerous microfibrils. The outline of the fibers was irregular with deep recesses filled with microfibrils. The ergastoplasm of the fibroblasts was well developed. The differential diagnosis with other connective dystrophies showed the original characteristic of this case. Clinically and histopathologically, the skin abnormalities are probably related to the deficiency in elastase inhibitor.     

Serum β2 microglobulin in recurrent aphthous stomatitis and Behçet's syndrome

β₂Microglobulin (β₂m), a constituent of cell surface histocompatibility antigens, was measured in scrum from twenty-eight patients with recurrent aphthous stomatitis, twenty-four patients with Behçet's syndrome and twenty-eight matched controls. Serum β₂m concentrations were significantly greater in recurrent aphthous stomatitis and in Behçet's syndrome than controls, but failed to differentiate the two diseases.     

Radioligand binding characteristics of β2–adrenoceptors of cultured melanoma cells

The existence of beta-adrenoceptors on intact cells of the human malignant melanoma cell line A-375 was investigated using the binding properties of the tritiated radioligand (-)-[3H]CGP-12177, a hydrophilic non-selective beta-adrenoceptor antagonist. Displacement experiments of the radioligand from its binding site were performed with antagonists and agonists to determine the beta-adrenoceptor subtype selectivity. The binding of (-)-[3H]CGP-12177 was saturable, of high affinity (KD = 0.025 nmol/l, n = 12) and was rapid and readily reversible. The maximal number of binding sites (Bmax) was 33.5 +/- 1.9 fmol/10(7) cells or 2018 +/- 114 receptors per cell. beta-adrenoceptor antagonists inhibited binding of the radioligand with monophasic displacement curves. IC50 values were (nmol/l): propranolol (non-selective) 2.82, alprenolol (non-selective) 2.0, ICI 118,551 (beta 2-selective) 3.5 and bisoprolol (beta 1-selective) 2200. Agonists inhibited binding in the order of potency of isoprenaline greater than adrenaline greater than noradrenaline. It is concluded that cells of the melanoma cell line A-375 contain a homogeneous population of beta 2-adrenoceptors.     

Loss of β2 microglobulin from the cell surface of cutaneous malignant and premalignant lesions

Biopsies from twenty-three patients with malignant skin lesions and from twenty-two patients with premalignant or benign skin lesions were stained for beta2 microglobulin by use of the immunoperoxidase technique. The results showed a significant loss of demonstrable surface beta2 microglobulin from the surface of malignant cells compared to benign, and a partial loss in the premalignant cases. This difference could prove to be a useful tool in the histological diagnosis of malignant skin lesions, and in assessing whether or not the lesion has been completely excised.     

埃兹蛋白在皮肤鳞癌、基底细胞癌中的表达及相关研究

目的 探讨埃兹（Ezrin）蛋白在皮肤基底细胞癌（BCC）和鳞状细胞癌（SCC）中的表达及在肿瘤侵袭转移过程中的作用.方法 采用免疫组化SP法检测Ezrin蛋白在皮肤BCC（30例）、SCC（32例）及正常皮肤对照组（10例）中的表达情况.结果 Ezrin蛋白在BCC、SCC及正常皮肤对照组中阳性表达率分别为60.0％、84.4％和10％.Ezrin蛋白在各组之间表达差异有统计学意义（P＜0.05）.Ezrin蛋白阳性表达与SCC的分化程度和淋巴结转移密切相关,各组间表达差异有统计学意义（P＜0.05）.结论 Ezrin蛋白的检测可能成为预测皮肤恶性肿瘤转移和预后的一项指标.     

The presence of β2 microglobulin on the membrane of the keratinocyte in premalignant skin disorders

Beta2 Microglobulin, the invariable light chain of the histocompatibility antigen, has proved to be absent on the cell surface of basal cell carcinoma. In actinically damaged skin and in patients with a past history of arsenic ingestion changes can be observed on the epidermal cell membrane which can predict malignancy before cell dysregulation is visible. The epidermis in the basal cell naevus syndrome behaves in this respect as normal epidermis and the spontaneous tumour growth cannot be explained by a predisposing defect in the HLA-antigens of the epidermal cell surface.     

Lack of intrinsic polarity in the ligandbinding ability of keratinocyte β1 integrins

Abstract: Within the basal layer of the epidermis the β1 integrins have a pericellular distribution. Two monoclonal antibodies, 15/7 and 12G10, that detect a conformation of the β1 integrin subunit that is induced following cation or ligand occupancy selectively recognized β1 integrins at the basement membrane zone in vivo and in focal adhesions of cultured keratinocytes; they did not recognize integrins on the apical and upper lateral membranes of basal keratinocytes nor integrins on the suprabasal keratinocytes of hyperproliferative epidermis. Inhibition of intercellular adhesion did not induce the 15/7 epitope on the lateral and apical membrane domains. The surface distribution of the epitopes was consistent with the antibodies acting as reporters of ligand-binding; in addition, the 15/7 epitope was exposed on unglycosylated, immature β1 integrins. Although the apical membrane of basal keratinocytes is not normally in contact with extracellular matrix proteins, we found that it was capable of binding fibronectin-coated beads and that the 15/7 epitope was exposed on plasma membrane in contact with the beads. When a chimeric molecule consisting of the extracellular domain of CD8 and the cytoplasmic domain of the β1 integrin subunit, used to mimic a constitutively active β1 heterodimer, was introduced into keratinocytes it localized to the basal, lateral and apical membrane domains. We conclude that although the conformation of the keratinocyte β1 integrins differs between the basal and the lateral/apical membrane domains there is no intrinsic polarity in the ligand binding potential of the receptors.     

Lichenoid skin lesions as a sign of β2-microglobulin-induced amyloidosis in a long-term haemodialysis patient

We report a case of β₂-microglobulin-induced amyloidosis. The patient was a 40-year-old man suffering from non-amyloid nephropathy, who had been treated by haemodialysis for 20 years. Lichenoid skin lesions, consisting of groups of pin-head-sized shiny papules, were present on the arms and trunk. On histological examination, amyloid deposits were present, principally in the dermal papillae, hut also around the sweat ducts and hair follicles. The amyloid displayed potassium-permanganate-resistant Congo red affinity, and green birefringence under polarized light, Immuno-histochemically, β₂-microglobulin was demonstrated in the lesions, confirming that they were a manifestation of β₂-microglobulin-associated amyloidosis. Skin lesions of this type have not been reported previously in β₂-microglobulin-associated amyloidosis.     

Basal Cell and Squamous Cell Carcinoma of the Skin in Finland

Long-term survival of patients with basal cell (BCC) and squamous cell carcinoma (SCC) of the skin and site distribution of the lesions were studied using ample nationwide cancer registry data. The material consisted of 23,975 patients with BCC and 2,927 patients with SCC diagnosed in Finland from 1967 to 1981. The proportion of patients with lesions in the head and neck region was 77.5% in men and 81.4% in women for BCC and, 75.7% in men and 75.8% in women for SCC. The 5- and 10-year relative survival rates (RSRs) of patients with BCC were very close to 100%. The 5-year RSR of patients with SCC diagnosed from 1974 to 1981 was 87.7% in men and 84.0% in women. In patients with SCC the worst prognosis was for lesions of the scalp and neck in men (80.2%) and for those of the ears in women (73.2%).     

皮肤鳞状细胞癌和基底细胞癌中细胞凋亡及c-fos、BNIP1表达

目的观察皮肤鳞状细胞癌(鳞癌)和基底细胞癌(基癌)中细胞凋亡及其与c-fos、BNIP1表达的关系。方法应用原位末端标记和原位杂交技术检测48例皮肤鳞癌和41例基癌标本中细胞凋亡及C-fos、BNIP1 mRNA表达。结果鳞癌中凋亡指数(AI)、c-fos mRNA表达明显高于基癌(P＜0．01),但BNIP1 mRNA表达在二者间的差异无显著性(P＞0．05)。AI在高分化鳞癌中明显增多(P＜0．05),但C-fos表达以低分化鳞癌更为明显(P＜0．05)。鳞癌中AI与c-fos、BNIP1表达呈显著正相关(P＜0．05)。结论鱗癌中细胞凋亡增多与c-fos表达上调相关,BNIP1在鳞癌和基癌中可能起促凋亡作用。     

α1-Antitrypsin deficiency in severe psoriasis

alpha 1-Antitrypsin phenotypes and trypsin-inhibitory capacities were measured in fifty-one patients with psoriasis. An increased number of variant phenotypes (MS, MZ, and SS) were found only in those patients with severe psoriasis (20% or more skin involvement) and not in those with lesser involvement. The psoriatic patients with variant phenotypes had an earlier disease onset than those psoriatic individuals (both mild and severe) without this association. Protease inhibitors may play a role in modifying disease activity in psoriasis.