人端粒酶逆转录酶在外阴白斑和外阴鳞癌中的表达

目的　研究人端粒酶逆转录酶 (hTERT)在外阴白斑和外阴鳞癌中的表达 ,探讨其在外阴白斑和外阴鳞癌发生、发展中的意义。方法　采用原位杂交法检测 80例外阴白斑、3 3例外阴鳞癌和 2 3例正常皮肤组织中hTERT的表达。结果　hTERT在外阴白斑各分型中阳性率分别为 :增生型 3 6.3 6% ,硬化萎缩型 4.17% ,混合型 2 3 .81% ,不典型增生型 46.15% ;在正常皮肤组织中阳性率为 13 .0 4% ;在外阴鳞癌中阳性率为 87.88% ,与外阴白斑和正常组织表达率相比差异有非常显著性 (P <0 .0 1)。hTERT在Ⅰ级、Ⅱ级、Ⅲ级外阴鳞癌中阳性表达率分别为 84.62 % (11/ 13 )、88.89%(8/ 9) ,90 .91% (10 / 11) ;鳞癌各级之间比较差异无显著性 (P >0 .0 5)。结论　原位杂交检测hTERT能够间接反映端粒酶活性 ,hTERT的异常表达可能与外阴白斑和外阴鳞癌的发生、发展有关     

外阴白斑和鳞癌细胞中P53和P21ras基因的检测

Ｐ５３和Ｐ２１ｒａｓ基因在正常细胞增殖调控过程中起着重要作用，已有研究证实，癌基因ｒａｓＰ２１和Ｐ５３的表达与肿瘤的生物学行为有密切关系［１，２］。本研究应用免疫组化方法，同时检测ｒａｓＰ２１及Ｐ５３在外阴白斑及鳞癌中的表达，旨在探讨其表达与外阴白斑的生物学行为的关系。材料和方法材料　１０２份标本来自西安市５家医院１９７０年～１９９１年病理ＨＥ染色确诊标本，根据Ｆｒｉｄｒｉｃｈ命名［３］，其中外阴白斑增生型２０例，硬化萎缩型２８例，混合型２３例，不典型增生８例，鳞癌２３例，并以２１例手术病人胸腹…     

外阴鳞癌皮损中HIF-1α蛋白的检测

目的探讨HIF—1α与外阴鳞癌的关系。方法用免疫组化SABC法检测HIF-1α在30例外阴鳞癌10例外阴正常皮肤中的表达情况。结果外阴鳞癌中Ⅰ-Ⅱ期HIF-1α阳性细胞数与Ⅲ-Ⅳ期相比差异有统计学意义(P<0.05);高分化与中分化和低分化相比差异有统计学意义(P<0.05)。无淋巴结转移与有淋巴结转移的相比差异有统计学意义(P<0.05)。结论HIF-1α的表达与外阴鳞癌的恶性进展有关,临床分期晚,分化程度差,有淋巴结转移的外阴鳞癌HIF-1α表达增高。     

黏膜疾病

20052492 外阴白斑和外阴鳞癌中基底膜蛋白的研究，20052493 长丝状疣样表现的假性湿疣1例，20052494 辨证治疗复发性口腔溃疡82例，20052495 加味六味地黄汤治疗复发性口腔溃疡疗效分析，20052496 酸甘化阴法治疗产后复发性口疮68例。     

基质金属蛋白酶10、金属蛋白酶组织抑制因子2等在皮肤鳞状细胞癌中的表达

目的 了解皮肤鳞状细胞癌(简称鳞癌)中基质金属蛋白酶10(MMP-10)、金属蛋白酶组织抑制因子2(TIMP-2)、Ⅳ型胶原(ColⅣ)和层粘连蛋白(LN)的表达及其与癌分化、淋巴结转移的关系。方法 用ABC免疫组化技术观察皮肤鳞癌患者的手术切除标本48例(高分化鳞癌34例,低分化鳞癌14例),其中伴淋巴结转移者12例。结果 MMP-10在低分化鳞癌中的表达明显高于高分化组(P<0.05),但其表达在淋巴结转移组与无转移组之间的差异无显着性(P>0.05).TIMP-2、ColⅣ和LN在高分化或无淋巴结转移的鳞癌中的表达明显高于低分化或有淋巴结转移者(P<0.05-0.01).结论 皮肤鳞癌中TIMP-2、ColⅣ和LN的表达与癌分化、淋巴结转移有关,而MMP-10表达仅与癌分化有关。     

环氧合酶-2在外阴上皮内非瘤样病变和外阴鳞癌中的表达

目的: 检测环氧合酶-2(COX-2)在外阴上皮内非瘤样病变和外阴鳞癌(VSCC)中的表达.方法: 采用免疫组化SABC方法检测COX-2在外阴上皮内非瘤样病变和VSCC及正常皮肤中的表达,用CD34标记测微血管密度(microvascular density, MVD)值.结果: COX-2在正常外阴皮肤中不表达,在两种上皮内非瘤样病变外阴鳞状上皮增生(SH)和外阴萎缩硬化性苔藓(LS)中表达,二者无显著性差异(P>0.05);在VSCC中表达明显升高,与外阴正常皮肤比较有显著性差异(P<0.05).在LS中MVD值与正常皮肤比较有显著差异(P<0.05);COX-2在有淋巴结转移组表达高于无淋巴结转移组(P<0.05);而在不同年龄组之间、临床分期和病理分级中,COX-2的表达差异无显著性(P>0.05).在VSCC中COX-2与MVD值呈正相关.结论: 在外阴鳞癌中,COX-2促进血管生成并增加外阴癌侵袭和转移的活性.     

外阴癌和外阴白斑的增殖细胞核抗原表达

外阴癌和外阴白斑之间的关系受到普遍关注，外阴白斑是否为癌前病变尚无定论。我们对外阴癌和外阴白斑患者皮损中增殖细胞核抗原（ＰＣＮＡ）的表达进行观察，现将结果报告如下。一、病例和方法１．所有病例均来自本院皮肤科和妇科的活检标本，其中现症病人４２例，以往诊断的石蜡组织块筛选出３８例，石蜡组织块作５ｕｍ切片，ＨＥ染色进行分级和分型。２．免疫组织化学染色采用抗增殖细胞核抗原的单克隆抗体ＰＣ１０，用ＡＢＣ法显示增殖细胞核抗原的表达。第一抗体为ＰＣＮＡ抗血清（Ｄａｋｏ公司生产），工作浓度１：５０，生物素标记的…     

C-erbB-1及C-erbB-2癌基因蛋白在外阴鳞癌及癌前病变中的表达

目的：探讨原癌基因Ｃ ｅｒｂＢ １、Ｃ ｅｒｂＢ ２和外阴癌发生的关系。方法：应用免疫组化ＡＢＣ法检测了１３２例外阴病变中原癌基因Ｃ ｅｒｂＢ １和Ｃ ｅｒｂＢ ２的表达。结果：两种癌基因在正常皮肤、外阴各型营养不良、不典型增生和鳞癌中的表达不同（Ｐ＜０．０５）。在各级鳞癌中表达则相反。结论：提示Ｃ ｅｒｂＢ １和Ｃ ｅｒｂＢ ２在外阴鳞状上皮增生、癌变和鳞癌生长的不同阶段均有不同作用。     

外阴白色病变36例分析

长期以来对外阴粘膜白斑的看法比较混乱，往往把外阴皮肤、粘膜变白、肥厚、萎缩都当作外阴白斑，但许多皮肤病都能引起外阴皮肤及粘膜的色素减少，现将我们１９９３年———１９９６年诊治的３６例回顾分析如下：一、临床资料：３６例均为门诊病人，其中男性１１例，女性...     

Survivin及p63蛋白在鳞状细胞癌皮损中的表达及其意义

目的：研究皮肤鳞癌组织中Survivin蛋白和p63蛋白的表达及其意义：方法：采用免疫组化法检测60例皮肤鳞癌组织中Survivin蛋白和p63蛋白的表达，探讨两者与鳞癌组织分化程度的关系。结果：Survivin蛋白在皮肤鳞癌组织中阳性表达率为73．3％，其表达越强，组织分化程度越低。p63在高分化鳞癌中呈环状分布于癌巢周围，低分化鳞癌中阳性细胞增多，分布紊乱，其表达在癌的不同分化中差异有显著性。结论：皮肤鳞癌中Survivin蛋白的表达与分化程度有密切关系，它的高表达提示肿瘤预后不良，也可能成为治疗皮肤鳞癌的重要新靶点。p63过度表达的癌细胞是获得了更具增殖、侵袭和间变能力的细胞。     

Basement membranes in experimentally induced skin tumors

Basement membrane changes in the epidermis and hair follicle apparatus resulting from topical 9,10-dimethylbenzanthracene applications were studied in mice, rats, and hamsters by light and electron microscopy and using antibodies to human collagen type IV and laminin. The basement membrane was distinct in epidermal hyperplasia, dysplasia, and papillomas, as well as around most of the keratoacanthomas and squamous cell carcinomas, which showed basement membrane irregularities, thickening, and reduplication in some areas. The invading edges of the squamous cell carcinomas with inflammatory infiltrates were devoid of laminin and collagen. Collagen IV and laminin-positive structures were observed around preserved follicular structures in rat: hair nevi and hair-follicle nevi, but partly absent around trichoepitheliomas and trichofolliculomas. Basal cell tumors were usually surrounded by a distinct basement membrane, which was lacking around some tumor cells.     

Loss of bullous pemphigoid antigen in peritumoral lacunas of basal cell carcinomas

Peritumoral lacunas of basal cell carcinoma (BCC) were for a long time misinterpreted as fixation artifacts. However, recent studies showed that they might be considered as a dynamic process related to degenerescence for the palisade cells. We studied three antigens of the epidermal basement membrane zone--type IV collagen, laminin, and bullous pemphigoid antigen--by indirect immunofluorescence in six cases of basal cell carcinoma. We could observe that type IV collagen as well as laminin were expressed as a linear continuous staining pattern surrounding each of the BCC buds. When there was a peritumoral lacuna, only the stroma side of the lacuna was stained. Bullous pemphigoid antigen showed either a linear continuous or discontinuous staining pattern along the basement membrane zone of the carcinomatous buds. At the site of a peritumoral lacuna bullous pemphigoid antigen abruptly disappeared. The loss of bullous pemphigoid antigen might be related to the lacuna formation.     

Immunohistochemical alterations in basement membrane components in skin cancer

To investigate alterations in the basement membrane (BM) components around tumor nests, Bowen's disease (BD), actinic keratosis (AK), basal cell epithelioma (BCE), squamous cell carcinoma (SCC) were studied by double immunofluorescent staining with antibodies to laminin (LN), type IV collagen (CIV), heparan sulfate proteoglycan (HSPG), and chondroitin 6-sulfate glycosaminoglycan (C6S). In BD, all BM components were continuous on the dermo-epidermal junction. In AK, C6S was partially disrupted, but the other components were continuous. In BCE, LN and CIV were continuous around the tumor nests, but HSPG and C6S were varied. SCCs were divided into two groups by the patterns of LN, CIV, and HSPG; SCC with continuous BM components or disrupted ones. The former SCC had a tendency to show the more infiltrative growth. C6S was detected partially on the BMs of SCCs which have cytological characteristics of BD, while it was absent on those of other SCCs. The difference in the patterns of the BM components suggests variation of tumor invasion.     

Occurrence of basement membranes in pigment cell tumors of the skin, relation to cell type and clinical behavior

The occurrence, location and intensity of the basement membrane (BM) components collagen IV and laminin in benign and malignant pigment cell tumors was studied by immunohistochemical methods. The results seemed to establish the following findings: junctional nevi display varying continuity of BM; nevus cells in the dermis display more continuous and thicker BM superficially (associated with epithelial type nevus cells); superficial spreading melanoma displays discontinuity of BM, and nodular melanoma and metastatic melanoma display variable BM around tumor aggregates. The variable expression of BM components in this study showed an apparent relationship to tumor cell type and laminin and collagen IV production, partly related to clinical behaviour.     

Immunofluorescent localization of type IV collagen and laminin in human skin and its application in junctional zone pathology

Purified antibodies against type IV collagen and laminin were used to localize basement membranes by indirect immunofluorescence in various anatomical regions of normal and diseased human skin. The two proteins showed extensive codistribution. A continuous linear staining was found along the epidermal-dermal junction and around hair follicles, sebaceous gland acini and small capillaries. The same proteins also surrounded individual cells such as those found in vessels, hair erector muscles and subcutaneous tissue. Blister formation in bullous pemphigoid left type IV collagen and laminin on the floor of the blister, while the bullous pemphigoid antigen as detected by human autoantibodies was found on both sides of the blister. In solid basal cell carcinoma a strong staining was found around all tumour islands as well as focally within the cell clusters. This suggests that the tumour cells produce these basement membrane proteins but have lost, at least in part, control of polar deposition.     

皮肤鳞状细胞癌中细胞外基质的分布形式与意义

目的 观察细胞外基质中纤连蛋白、层粘连蛋白在皮肤鳞状细胞癌(鳞癌)中的分布形式,探讨其与癌生物学行为的关系.方法 用纤连蛋白、层粘连蛋白、增殖细胞核抗原、p53抗体对50例皮肤鳞癌作免疫组化染色.结果 纤连蛋白、层粘连蛋白在皮肤鳞癌中显示3种分布形式,不连续巢周型、碎片型、血管间质型,这3种分布形式与癌生长、分化、增殖密切相关,3例分化好的膨胀巢状生长,在癌巢周有连续线状纤连蛋白、层粘连蛋白分布.结论 皮肤鳞癌中纤连蛋白、层粘连蛋白明显减少,浸润性癌中不一定均有基膜缺乏,癌浸润后可能需经过灶性组织分化,再进一步浸润与转移,纤连蛋白、层粘连蛋白的分布形式反应了癌的恶性程度.     

A unique epithelial basement membrane antigen defined by a monoclonal antibody (KF-1)

The basement membrane zone (BMZ) of human skin is a complex structure which contains several well-defined components including bullous pemphigoid antigen, laminin, type IV collagen, and proteoglycan. Characterization of additional basement membrane (BM) constituents has been limited by their relative inaccessibility, insolubility, and low tissue concentration. We have produced a murine monoclonal antibody that has enabled us to define a unique constituent of the BMZ of human stratified squamous epithelia. The monoclonal antibody (KF-1) was raised by standard techniques using suction blister-derived trypsinized human epidermal cells as the antigen. Indirect immunofluorescence and immunoperoxidase staining of human and rhesus monkey tissues with KF-1 produced linear BMZ staining of stratified squamous epithelia. Glandular and vascular BMs were not stained. Immunoelectron microscopic studies of normal human skin and esophagus showed specific binding of KF-1 to the lamina densa of the BMZ, a localization identical to that of type IV collagen. However, unlike type IV collagen, which is not species specific and is found in all BMs, the antigen defined by KF-1 is collagenase-resistant and is specific for primate stratified squamous epithelia. These findings confirm the existence of regional variation in BM composition, and demonstrate for the first time that the lamina densa of stratified squamous epithelial BMs contains a constituent other than type IV collagen.     

Immunohistochemical alterations in basement membrane components of squamous cell carcinoma

To investigate alterations in the basement membrane (BM) in squamous cell carcinoma (SCC), we investigated 20 tumors. Four had the cytologic characteristics of Bowen's disease (SCC-BD) and 16 did not have them (SCC-NB). Tumors were studied immunohistochemically by double immunofluorescent staining by using mouse monoclonal antibodies to the core protein of heparan sulfate proteoglycan (HSPG) and chondroitin 6-sulfate glycosaminoglycan (Ch6S) as well as rabbit antiserum to laminin (LN) and type IV collagen (C-4). In well-differentiated and highly keratinized SCC-NB, LN, C-4, and HSPG could be detected in the tumor nest BM and showed no loss of continuity, but they were largely lost in poorly differentiated and poorly keratinized SCC-NB. This suggests that poorly differentiated SCC-NB cause greater enzymatic degradation of BM components than well-differentiated SCC-NB. Ch6S was detected in parts of the BM of SCC-BD, but it was absent in all SCC-NB examined. It appears that SCC-NB have lost the ability to synthesize Ch6S, and that SCC-BD degrade Ch6S although they continue to produce it. Thus, it appears that in SCC the BM is qualitatively different from that of normal epidermis, and that SCC-BD can be distinguished from SCC-NB by the Ch6S content of the BM.     

Expression of basement membrane proteins and interstitial collagens in dermal papillae of human hair follicles

The expression of basement membrane molecules and interstitial collagens in human hair follicle mesenchyme was studied by immunohistochemical staining of tissue sections and of cells cultured from dermal papillae. Type I and type III collagens were found in the dermal sheath and in the dermal papilla throughout the hair cycle. Laminin and type IV collagen were expressed at the outer root sheath basement membrane and in the extracellular matrix of the dermal papilla of anagen and catagen follicles. In telogen follicles, where the volume of the dermal papilla extracellular matrix is much reduced, outline staining of dermal papilla cells for laminin and type IV collagen was still apparent. Staining for bullous pemphigoid antigen was also seen at the outer root sheath basement membrane extending to the lower tip of the hair bulb. In anagen follicles, there was no staining for bullous pemphigoid antigen at the interface between hair bulb epithelium and the dermal papilla and no staining within the dermal papilla. However, linear staining for bullous pemphigoid antigen became continuous around hair follicle epithelium during catagen and telogen. Cells cultured from human dermal papillae also stained for interstitial collagens, type IV collagen and laminin. However, similar results were obtained when cultured dermal fibroblasts were stained with the same antibodies. The expression of basement membrane proteins in human dermal papillae resembles that seen in follicles from other mammalian species and suggests that this is relevant to dermal papilla function. Cultured dermal papilla cells express a similar pattern of interstitial collagens and basement membrane proteins to those seen in tissue sections but this finding is not specific to dermal papilla cells.     

Immunoelectron microscopic study of the basement membrane in oral lichen planus

The present study investigated the nature of basement membrane changes in oral lichen planus. For this purpose antibodies to type IV collagen, laminin and fibronectin were applied in avidin-biotin peroxidase complex staining using a pre-embedding immunoelectron microscopy technique. Immunoreactivity to type IV collagen and laminin was restricted to the sub-basal basement membrane and the basement membrane branches extending into the lamina propria. Immunoreactivity to fibronectin was noted also in the connective tissue as a network-like arrangement of thin strands. Although local activated CDB+ cytotoxic lymphocytes and tissue macrophages may be involved in the local pathogenetic process, these findings suggest that the basement membrane alterations are secondary to pathologic changes in the basal cells.