脂溢性角化病、基底细胞癌和鳞状细胞癌中几种Smad蛋白质表达的检测

目的：探讨转化生长因子（TGF）-β信号转导途径中Smad1、Smad2、Smad3（Smad1／2／3）,磷酸化Smad2,磷酸化Smad3（p-Smad2／3）Smad4蛋白在脂溢性角化病、基底细胞癌和鳞状细胞癌中的表达特点及其意义。方法：采用EliVision^TMplus免疫组化技术分别检测脂溢性角化病、基底细胞癌、鳞状细胞癌以及正常对照皮肤中Smad1／2／3、p-Smad2／3、和Smad4的表达情况。结果：Smad1／2／3、p-Smad2／3和Smad4蛋白在脂溢性角化病、基底细胞癌和鳞状细胞癌中的表达较正常表皮显著降低。结论：脂溢性角化病、鳞状细胞癌和基底细胞癌中Smadl／2／3、p-Smad2／3和Smad4蛋白表达降低可能通过阻断TGF—B信号转导,有助于上述表皮肿瘤的形成和发展。     

成纤维细胞生长因子10mRNA在脂溢性角化病皮损中的表达

目的研究成纤维细胞生长因子10 mRNA在脂溢性角化病皮损中的表达,探讨其在脂溢性角化病发病中的作用机制。方法应用原位杂交法检测FGF10 mRNA正常皮肤组织和脂溢性角化病皮损中的表达和分布。结果28例脂溢性角化病皮损表皮的全层或中下层均可见FGF10 mRNA表达(100.0%);正常皮肤表皮的基底层或个别细胞内可见FGF10 mRNA的表达(3.57%);脂溢性角化病皮损表皮中FGF10 mRNA的表达明显高于正常对照组(P<0.05)。结论FGF10 mRNA在脂溢性角化病皮损中表达增高。     

Smad7在脂溢性角化病、日光性角化病及基底细胞癌中的表达

目的： 检测Smad7在脂溢性角化病、日光性角化病以及基底细胞癌中的表达。方法：对脂溢性角化病、日光性角化病及基底细胞癌标本（各30例）和30例正常标本进行免疫组化染色。结果：23例脂溢性角化病标本、23例日光性角化病标本和28例基底细胞癌标本中Smad7染色阳性,阳性细胞率分别为（31.0±23.0）%,（32.7±26.3）%和（62.6±32.1）%,均显著高于正常组织的（6.7±5.0%）。结论： Samd7可能与脂溢性角化病、日光性角化病以及基底细胞癌的发病有关。     

EGF、EGFr在脂溢性角化病组织中的表达

为探讨以皮肤衰老为特征之一的脂溢性角化病（seborrheic keratosis,SK)病变组织中角质形成细胞成熟迟缓的发病机理,采用免疫组织化学二步法对32例脂溢性角化病皮损组织及作对照的10名正常皮肤组织石蜡标本中表皮生长因子（EGF）及其受体（EGFr)进行检测。结果SK组的EGF和EGFr在阳性表达强度上均高于正常对照组（P＜0．01）,EGFr在脂溢性角化病皮损角质层,颗粒层和棘细胞上层中有广泛的表达,并且棘层肥厚伴角化过度或乳头状瘤样增殖者表达呈强阳性。提示EGF和EGFr的这种异常或超表达可能与脂溢性角化病角质形成细胞的过度增殖的发生有一定的关系。     

共聚焦激光扫描显微镜鉴别脂溢性角化病与鲍恩病

目的：探讨共聚焦激光扫描显微镜（CLSM）在脂溢性角化病与鲍恩病鉴别中的应用价值。方法选88例临床诊断为脂溢性角化病和18例临床诊断为鲍恩病的患者典型皮损做CLSM检查,然后取该处皮损行组织病理学检查。结果脂溢性角化病CLSM图像特征：全部有表皮脑回状结构,另有角蛋白充填的囊性包裹体,表皮突呈小梁状下延;基底层细胞排列呈条索状或放射状9例,基底层及真皮层可见折光性明亮的结构6例。鲍恩病CLSM图像特征：表皮中下层细胞灶状排列紊乱,体积较大,细胞形态不规则,有明显的异形,真皮浅层散在单个核细胞浸润。结论脂溢性角化病与鲍恩病在CLSM成像上有不同的特征性,CLSM可为二者的鉴别诊断提供帮助。     

β-连环蛋白在基底细胞癌中的表达及意义

目的：探讨β-连环蛋白（β-catenin）在基底细胞癌中的表达及意义。方法：应用免疫组化PowerVision^TM二步法检测25例基底细胞癌患者皮损中β-连环蛋白的表达情况,同时以20例脂溢性角化病患者作对照。结果：β-连环蛋白在基底细胞癌皮损中异位表达率为92％,显著高于脂溢性角化病（55％）（P〈0．05）。结论：β-连环蛋白表达异常在基底细胞癌发生、发展中可能起重要作用。     

内皮素-1、内皮素转化酶-1和 肿瘤坏死因子-α在脂溢性角化病皮损中的表达

目的: 探讨内皮素-1（ET-1）、内皮素转换酶-1( ECE-1)和肿瘤坏死因子-α（TNF-α）在脂溢性角化病(seborrheic keratosis , SK) 皮损出现色素沉着的发病机制。方法: 采用免疫组化SP 法检测30 例脂溢性角化病(SK) 皮损组织中ET-1、ECE-1和 TNF-α的表达,并选用10 例正常皮肤组织作为对照。结果:SK组中ET-1、ECE-1和 TNF-α的阳性表达程度分别显著高于对照组。结论: SK组织中存在ET-1、ECE-1和 TNF-α的过度表达,这种异常高表达的ECE-1和 TNF-α可能通过参与脂溢性角化病(SK)的自分泌生长环路而上调ET-1的表达，并且与脂溢性角化病(SK)的色素沉着有关。     

桥粒芯糖蛋白1在不同表皮肿瘤中表达的研究

目的：了解桥粒芯糖蛋白1与表皮肿瘤的病理及生物学行为之间的关系。方法：采用过氧化物酶标记的链霉卵白素免疫组织化学染色方法，检测了桥粒芯糖蛋白1(Dsgl)在鳞状细胞癌、基底细胞癌、Bowen病、日光角化病、角化棘皮瘤、脂溢性角化病及正常皮肤中的表达。结果：Dsgl在正常表皮中显著表达；在鳞状细胞癌和基底细胞癌的肿瘤组织中表达显著减弱或消失；在Bowen病和日光角化病细胞间变区域无表达；在绝大多数角化棘皮瘤、脂溢性角化病中的表达为强而连续的胞膜染色，与正常表皮中的表达相似。结论：皮肤恶性肿瘤中Dsgl的表达显著减弱或消失，可能与肿瘤的侵袭性和转移有关，Dsgl可能对表皮良、恶性肿瘤的鉴别诊断具有一定价值。     

基因工程抗角蛋白抗体在正常皮肤和几种表皮增生性皮肤病皮损中的反应定位

目的　探索一株基因工程人源性抗角蛋白Fab抗体在正常皮肤及几种表皮增生性皮肤病皮损中的反应定位。方法　利用从噬菌体抗体库中筛选到的特异表达抗角蛋白Fab片段的质粒转化大肠杆菌 ,IPTG诱导表达出Fab抗体 ,纯化鉴定后用此抗体对正常皮肤及银屑病、鳞癌、基底细胞癌和脂溢性角化病皮损进行免疫组化染色。结果　正常皮肤表皮呈阴性染色 ,毛囊呈阳性染色 ,银屑病、鳞癌、基底细胞癌和脂溢性角化病皮损均呈现明显的阳性着色 ,其中银屑病皮损基底细胞层为强阳性。所有细胞染色部位均位于胞质 ,胞核未见着色 ,真皮为阴性。结论　该株人源性抗角蛋白Fab抗体主要与表皮组织结合 ,对银屑病等表皮增生性皮肤病的损害具有较高特异性。     

P16、P21WAF1/CIP1、PCNA和cyclin E在脂溢性角化病中的表达及其意义

目的：研究脂溢性角化病皮损组织中P16、P21^WAF1/CIP1、PCNA、cyclinE四种细胞周期素相关因子的表达及意义。方法：应用免疫组化PV法（改进的SP法），对50例脂溢性角化病病人和10例正常人皮肤进行P16、P21^WAF1/CIP1、PCNA、cyclinE四种细胞周期素相关因子的测定。结果：脂溢性角化病患者中这四种因子的表达阳性率分别为：78％、68％、70％、46％；而正常对照组的阳性率仅为：40％、30％、50％、10％。结论：P16、P21^WAF1/CIP1、PCNA、cyclinE四种细胞周期素相关因子在脂溢性角化病的发病中可能起重要作用。     

Clonal nature of seborrheic keratosis demonstrated by using the polymorphism of the human androgen receptor locus as a marker

We evaluated the clonality of seborrheic keratoses using a polymorphism due to the random inactivation of one of two X chromosomes in females. Thirty-eight seborrheic keratoses obtained from the skin of females with polymorphism of the human androgen receptor (HUMARA) locus were examined by a fluorescent polymerase chain reaction procedure, which allowed accurate measurement of the peak intensities of each HUMARA allele. The epithelial portion of seborrheic keratosis and normal control epidermis adjacent to the seborrheic keratosis were removed by laser capture microdissection. As biopsied specimens of seborrheic keratoses contained small amounts of normal epidermis, the effect of digestion by a restriction enzyme (HhaI) recognizing the nonmethylated active sites was compared between seborrheic keratoses and normal control epidermis in only five seborrheic keratosis cases. Disappearance or significant reduction in intensity of one of two HUMARA alleles was observed after HhaI digestion in seborrheic keratoses, but not in the normal control epidermis. Although the skewing of the polymorphism was not corrected by the normal control epidermis in the remaining 33 seborrheic keratosis cases, one of two HUMARA peaks practically disappeared after HhaI digestion in 20 of 33 seborrheic keratosis cases. In total, 25 of 38 seborrheic keratoses were considered to be monoclonal. The histologic type of seborrheic keratoses did not affect clonality.     

Differentiation disorders of keratinocytes in seborrheic keratosis (acanthotic type).

Since the differential disorder of keratinocytes in seborrheic keratosis remains to be elucidated, the differentiation of seborrheic keratosis (acanthotic type) was examined immunohistochemically using a lectin and two anti-keratin monoclonal antibodies. A lectin, peanut agglutinin (PNA), and anti-keratin monoclonal antibody, 34 beta B4, recognize the whole epidermis except for the basal layer in the normal epidermis. In seborrheic keratosis (acanthotic type), cells unstained with either PNA or 34 beta B4 were found throughout the entire tumor. In the upper part of the tumor, some cells appeared to undergo keratinization without expressing the differential markers recognized by PNA or 34 beta B4. Another anti-keratin monoclonal antibody, 34 beta E12, stained the tissues in the same way as in the normal epidermis. Thus it was indicated that, in seborrheic keratosis (acanthotic type), although differentiation was partially maintained, some cells might undergo maturation without expressing the differentiation markers recognized by PNA or 34 beta B4.     

Two Cases of Basal Cell Carcinoma Arising in Seborrheic Keratosis

The present study reports two cases of basal cell carcinoma arising in seborrheic keratosis. The first case is a seventy-three-year-old female who presented with a blackish nodule arising from a pigmented lesion on her chest. Histopathological analysis of the nodule and the pigmented lesion revealed a basal cell carcinoma with hair follicular differentiation and an acanthotic seborrheic keratosis, respectively. The second case is a seventy-year-old female with a blackish nodule arising from a pigmented lesion on her back. Histological analysis of the nodule revealed an atypical basaloid cell mass surrounded by a seborrheic keratosis lesion. In addition to the coexisting seborrheic keratosis with the basal cell carcinoma, a basaloid follicular hamartoma that showed muliple hamartomatous hair follicles or small cysts replaced by a branching cord or lace-like network of basaloid cells surrounded by fibrovascular stroma was identified. We concluded that both cases presented a rare combination of a seborrheic keratosis which underwent a malignant change to basal cell carcinoma. It appears that both basal cell carcinomas and seborrheic keratosis may derive from a similar source: pluripotential cells of either the epidermis or hair follicle epithelium.     

EGFR、PTEN、c-Jun和MMP-1在面部脂溢性角化病中的表达及意义

目的:检测皮肤光老化传导通路中的4个关键因子表皮生长因子受体(EGFR)、10号染色体同源丢失性磷酸酶-张力蛋白(PTEN)、转录因子活化蛋白-1(AP-1)的主要组分c-Jun、以及基质金属蛋白酶-1(MMP-1)蛋白在面部脂溢性角化病(SK)及面部正常皮肤组织中的表达,探讨SK的发病与皮肤光老化的相关性。方法:应用免疫组织化学染色及EVG染色技术检测54例面部SK患者皮损标本和20例面部正常者皮肤标本(对照组)中EGFR、PTEN、c-Jun和MMP-1的蛋白表达及弹力纤维的含量变化情况。结果:SK组中的EGFR、c-Jun和MMP-1表达均高于对照组(Z值分别为-4.45,-2.33,-2.37,P值均<0.05),PTEN的表达略低于对照组(Z=-1.55,P>0.05);Spearman等级相关分析表明SK皮损中EGFR、c-Jun与MMP-1表达呈正相关(r值分别为0.71、0.69,P值均<0.05),PTEN与MMP-1的表达呈负相关(r=-0.31,P<0.05);SK皮损下方真皮中弹力纤维变性情况较对照组明显,且皮损下方弹力变性组织堆积随年龄增长而增加(P<0.05),而胶原蛋白减少。结论:与皮肤老化有关的生物学指标EGFR、c-Jun、PTEN、MMP-1表达的变化及真皮中弹力纤维变性增加,提示皮肤光老化与SK的发生相关,面部SK可能是在光老化的基础上产生。     

共聚焦激光扫描显微镜在不典型汗管瘤中的应用

目的探讨皮肤共聚焦激光扫描显微镜(CISM)诊断汗管瘤的应用价值。方法对24例临床诊断为扁平疣、脂溢性角化病但不排除汗管瘤的患者,选定典型皮损做CLSM检查,后取该处皮损行组织病理学检查。结果 CLSM图像显示表皮大致正常,真皮浅层或中层可见圆形、卵圆形的高折光性结构,组织病理检查结果提示表皮大致正常,真皮内可见多数导管、小的囊腔及由上皮细胞所组成的小细胞巢及索,这与CLSM图像下的高折光性结构一致。结论 CLSM是诊断汗管瘤及鉴别扁平疣、脂溢性角化病等皮肤病非常有用的辅助工具。     

Trichilemmal tumor arising in a seborrheic keratosis: analysis of cell kinetics by BrdU staining.

We report a case of a 74-year-old male with a trichilemmal tumor arising in a seborrheic keratosis on the buttock and the results of a cell kinetic study of this tumor using a BrdU staining method. The incidence of trichilemmal tumor arising in a seborrheic keratosis seems to be extremely rare. The labeling index of this tumor was 12.0%; this was a level intermediate between normal epidermis and a variety of hyperproliferative skin diseases such as squamous cell carcinoma, Bowen's disease, and psoriasis vulgaris. DNA replicating cells were present in the germinative layers in normal epidermis and the benign hyperproliferative skin diseases, psoriasis vulgaris. In contrast, DNA replicating cells were found throughout the entire epidermis in premalignant and malignant tumors such as in Bowen's disease and squamous cell carcinoma. In this case, DNA replicating cells were localized mainly in the basal and parabasal cell layers, but also seen in the upper squamous layers. These findings suggest that this trichilemmal tumor had a malignant tendency, though it was slow-growing and relatively benign in nature.     

脂溢性角化病皮损Survivin表达的免疫组化观察

目的观察脂溢性角化症的各病理分型对Survivin染色的表达情况。方法脂溢性角化症患者63例,组织病理分型,免疫组化ABC法进行Sunrivin染色观察。结果脂溢性角化症的各病理分型染色结果显示①棘层肥厚型14/21例阳性,7/21例弱阳性;②角化过度型:16/20例染色阳性,4/20例显示较弱染色;③腺样型:9/13例染色阳性,4/13弱染色;④刺激型:1/9例弱染色,其余染色阴性。结论脂溢性角化病普遍表达Survivin,提示其发病可能与凋亡抑制相关。