Survivin和p53在皮肤癌中的表达及其临床意义

为检测凋亡抑制基因Survivin和p53基因在皮肤鳞状细胞癌(SCC)和基底细胞癌(BCC)中的表达及临床意义.用免疫组织化学SP法对40例BCC,30例SCC,18例脂溢性角化(SK),16例正常皮肤组织石蜡标本进行Survivin和p53蛋白表达的检测和分析.(1)Survivin在BCC、SCC中的表达阳性率分别为70%和80%,明显高于正常皮肤和SK组(P＜0.01).(2)p53在BCC和SCC中的阳性表达率分别为:45%和56.67%,明显高于正常皮肤和SK组(P＜0.01).(3)BCC和SCC中Survivin与p53的表达呈正相关(r=0.373,r=0.404,P＜0.05).凋亡抑制基因Survivin可能参与BCC和SCC的发生发展,Survivin和p53的检测对BCC和SCC的诊断和进一步治疗提供有效的依据.     

Livin,Survivin和Fas在脂溢性角化病中的表达

目的观察Livin在皮肤脂溢性角化病(SK)皮损中的表达情况,探讨其与Survivin和Fas表达的相互关系及临床意义。方法采用免疫组化SP法检测40例SK组织中Livin,Survivin和Fas的表达情况,并以10例正常包皮组织作为对照。结果 Livin和Survivin在SK组织中的阳性表达率(72.50%和77.50%)均高于正常包皮组织(10.00%和20.00%),差异均有统计学意义(P均<0.05)。Fas在SK标本中的阳性表达率(97.50%)与正常包皮组织(90.00%)比较,差异性无统计学意义(P>0.05)。Livin和Survivin在SK中的表达呈正相关(P<0.05),两者表达强度差异无统计学意义(P>0.05);Livin和Fas在SK中的表达呈显著负相关(P<0.05),两者表达强度差异有统计学意义(P<0.05)。Livin和Survivin在SK组织中的表达与患者年龄、病程长短有关(P均<0.05),而与患者性别、皮损大小、发病部位、皮损数目无关(P均>0.05)。结论 SK的发生可能与Livin基因表达上调有关;Livin与Survivin两者在SK组织细胞凋亡过程中可能存在相同路径;Livin与Fas两者在SK组织细胞凋亡过程中可能存在拮抗作用。     

组织蛋白酶B,Ki67在皮肤鳞状细胞癌、基底细胞癌和脂溢性角化病的表达

目的观察组织蛋白酶B(CB)、细胞增殖核抗原(Ki67)在皮肤鳞状细胞癌(SCC)、基底细胞癌(BCC)和脂溢性角化病(SK)等组织中的表达,并分析其表达差异的意义。方法用免疫组化SP染色法检测CB,Ki67在15例SCC,15例BCC,14例SK及10例正常对照皮肤组织中的表达。结果 CB在正常皮肤组织表达为阴性,在SK,BCC,SCC瘤组织中表达依次升高,差异有显著性(P0.05);Ki67在SK,BCC和SCC三者表达差异亦有显著性(P0.05)。结论 CB,Ki67在SK,BCC和SCC瘤组织中的阳性表达率依次升高,可能与SCC侵袭和转移有关。     

PTEN,Ki-67和CyclinD1在皮肤鳞状细胞癌中的表达及意义

目的探讨PTEN,Ki-67和CyclinD1在皮肤鳞状细胞癌发生发展中的作用及意义。方法采用免疫组化EnVision染色法检测PTEN,Ki-67和CyclinD1在30例皮肤鳞状细胞癌石蜡包埋组织、15例正常皮肤组织中的表达。结果①PTEN在皮肤鳞状细胞癌组织中的表达率较对照组低(P<0.05),与肿瘤分级无相关性(P>0.05);②Ki-67在皮肤鳞状细胞癌组织中的表达率较对照组高(P<0.01),与肿瘤分级相关(P<0.01);③CyclinD1在皮肤鳞状细胞癌组织中的表达率较对照组高(P<0.01),与肿瘤分级相关(P<0.05);④PTEN与Ki-67在皮肤鳞状细胞癌中表达呈负相关(r=-0.411,P<0.05);PTEN与CyclinD1在皮肤鳞状细胞癌中表达呈负相关(r=-0.386,P<0.05);Ki-67和CyclinD1在皮肤鳞状细胞癌中表达呈显著正相关(r=0.623,P<0.01)。结论①PTEN在抑制皮肤鳞状细胞癌的发生发展中存在一定相关性,但与该肿瘤恶性分化程度的关系尚不明确;②Ki-67在皮肤鳞状细胞癌中阳性表达上调,与该肿瘤的分级呈正相关;③CyclinD1在皮肤鳞状细胞癌中阳性表达上调,与该肿瘤的分级呈正相关;④PTEN,CyclinD1与Ki-67三者中两两之间的相互关系反应了抑癌基因与癌基因相互协调、相互促进的关系。     

性传播疾病

20072614PCNA、p53、Ki-67在尖锐湿疣中的表达和意义/林友胜(四川省卫生干部管理学院),张玉梅∥四川医学.-2007,28(3).-322~323运用免疫组化法检测PCNA、p53、Ki-67在尖锐湿疣(CA)中的表达,结果PCNA在CA组阳性表达率与正常对照组比较差异无统计学意义(P>0.05),但CA组PCNA强阳性率显著高于对照组(P<0.05)。p53在CA组阳性表达率明显高于正常对照组,差异具有统计学意义(P<0.05)。Ki-67在CA组阳性表达率与正常对照组差异无统计学意义(P>0.05),但CA组Ki-67强阳性率也显著高于对照组(P<0.05)。表3参8(惠海英)20072615CD105和p63在…     

Survivin和COX-2在鲍温病和皮肤鳞状细胞癌中的表达及意义

目的探讨鲍温病及皮肤鳞状细胞癌组织中凋亡抑制蛋白生存素(Survivin)和环氧合酶-2(COX-2)的表达及意义。方法用免疫组化SP法分别检测Survivin蛋白和COX-2蛋白在19例鲍温病组织、25例皮肤鳞状细胞癌组织及17例正常皮肤组织中的表达。结果 Survivin蛋白和COX-2蛋白在鲍温病组织及鳞癌组织中的阳性表达率明显高于正常组,二者在鳞癌组织中的阳性率与鲍温病组织中阳性率差异有统计学意义(P0.01);Survivin和COX-2的阳性表达呈正相关(r=0.764,P0.05)。结论 Survivin蛋白和COX-2蛋白参与了鲍温病及皮肤鳞状细胞癌的发生、发展,二者在抑制细胞凋亡方面可能存在协同作用。     

MIC-1和uPA蛋白在皮肤鳞状细胞癌组织中的表达及与组织学分级和发病部位的关系

目的 探讨MIC-1和uPA蛋白在皮肤鳞状细胞癌中的表达及与组织学分级和发病部位的关系。方法 应用免疫组化SP法检测42例皮肤鳞状细胞癌组织及42例正常对照皮肤中MIC-1及uPA蛋白的表达,并分析其与组织学分级及发病部位的关系。结果 皮肤鳞状细胞癌组织中MIC-1(66.67%)及uPA蛋白(78.57%)阳性表达率均显著高于正常对照皮肤组织中的阳性表达率(16.67%和28.57%),差异均有统计学意义(P均<0.05);皮肤鳞状细胞癌组织中MIC-1及uPA蛋白阳性表达率均与鳞状细胞癌病理组织学分级密切相关(P均<0.05);MIC-1与uPA蛋白的表达呈正相关(P<0.05)。结论 皮肤鳞状细胞癌组织中MIC-1和uPA蛋白的表达均显著升高,其高表达可能与皮肤鳞状细胞癌发生和发展有关。     

P105,CD105和PTEN在皮肤鳞状细胞癌中的表达及相关性分析

目的观察皮肤鳞状细胞癌(SCC)中P105,CD105和PTEN蛋白的表达情况,探讨其表达与临床病理特征的关系。方法用免疫组化SP法检测52例皮肤鳞状细胞癌组织和10例正常皮肤组织石蜡标本中P105和PTEN蛋白的表达,按Weidner法计算CD105蛋白标记物的肿瘤组织微血管密度(MVD)。结果在SCC标本中,P105蛋白阳性表达率与CD105标记的MVD值明显高于正常皮肤组织;PTEN蛋白阳性表达率明显低于正常皮肤组织。在低分化SCC标本中,P105和CD105蛋白的阳性表达率高于高中分化组,PTEN蛋白的阳性表达率低于高中分化组;P105和CD105蛋白的阳性表达与病理分级呈明显正相关,PTEN蛋白阳性表达与病理分级呈明显负相关,差异均有统计学意义(P均<0.05)。结论在SCC组织标本中,P105和CD105强表达,PTEN蛋白低表达或不表达,这可能是细胞恶性转化和增殖的信号,也是肿瘤具有侵袭性的标志。     

蛋白激酶D1及其磷酸化位点在皮肤鳞状细胞癌、Bowen病及光线性角化病组织中的表达

目的 探讨蛋白激酶DI(PKD1)及其磷酸化位点pPKD1-tyr463和pPKD1-ser916在鳞状细胞癌(SCC)、Bowen病和光线性角化病(AK)中的表达及意义.方法 收集新鲜SCC、Bowen病、AK及正常皮肤组织各10份,RT-PCR法检测各组样本中PKD1在基因水平的表达,Western印迹法检测各组样本中PKD1及其磷酸化位点在蛋白水平的表达.另收集蜡块组织SCC 50份、Bowen病20份、AK 20份及正常表皮组织10份,免疫组化检测PKD1、pPKD1-tyr463及pPKD1-ser916的表达情况.结果 正常皮肤组织、SCC、Bowen病和AK组织中PRKD1 mRNA的表达量分别为0.64±0.09、5.37±1.06、2.69±0.72和2.43±0.46,4组间差异有统计学意义(F=21.37,P＜0.05),且SCC、Bowen病和AK组织的表达水平均显著高于正常组织(P＜0.05),SCC组织又显著高于AK和Bowen病组织(均P＜ 0.05),而Bowen病与AK组织的表达量差异无统计学意义(P＞0.05).PKD1总蛋白及pPKD1-tyr463在SCC和Bowen病组织中主要表达在棘层细胞及异形细胞的细胞质和细胞膜,且阳性表达率均显著高于正常皮肤组和AK组(均P＜0.01);pPKD1-ser916仅在部分高分化SCC癌巢中少量表达,而低分化鳞癌、AK、Bowen病及正常皮肤组织中均未见表达;SCC组中PKD1阳性表达率随鳞癌病理分级的提高而增加,且PKD1与pPKD1-tyr463的表达呈正相关(rcc=0.479,P＜0.05).Western印迹检测结果与免疫组化检测结果大致相符.结论 PKD1及其磷酸化位点Tyr463可能参与复层鳞状上皮来源的皮肤肿瘤的形成和进一步发展分化,在皮肤SCC形成进程中PKD1可能通过Tyr463位点活化而发挥促进作用.     

ARID1A､PIK3CA､Ki-67在不同病变级别､浸润性膀胱尿路上皮癌中的表达及对肿瘤复发的影响

目的探讨AT丰富结合域1 A(ARID1 A)?磷脂酰肌醇激酶-3催化亚单位α基因(PIK3 CA)?细胞增殖核抗原67(Ki-67)在不同病变级别?浸润性膀胱尿路上皮癌(BUC)中的表达情况及对肿瘤复发的影响。方法选取2018年5月至2019年8月保定市第二医院收治的107例BUC患者作为研究对象。均通过手术或膀胱镜活检取癌组织,并取其中28例患者的癌旁正常组织标本(距癌旁>2cm)作为对照。对比不同组织中ARID1 A?PIK3 CA?Ki-67蛋白表达。治疗后随访6个月,根据是否复发将患者分为复发组(n=27)和未复发组(n=80),分析BUC复发的影响因素,以及ARID1 A?PIK3 CA?Ki-67蛋白表达与病变分级?临床分期的关系。结果BUC患者癌组织ARID1 A蛋白阳性率低于癌旁正常组织,PIK3 CA?Ki-67蛋白阳性率高于癌旁正常组织,差异具有统计学意义(P<0.05);复发组年龄?病变级别?临床分期?病灶个数?PIK3 CA蛋白阳性表达率与未复发组比较,差异具有统计学意义(P<0.05);两组ARID1 A?Ki-67蛋白阳性表达率比较,差异无统计学意义(P>0.05);随着年龄?病变级别?临床分期?病灶个数?PIK3 CA蛋白阳性表达率升高,BUC患者复发风险增加(P<0.05);BUC患者病变级别?临床分期越高,PIK3 CA?Ki-67蛋白阳性表达率越高,ARID1 A蛋白阳性表达率越低(P<0.05)。结论BUC患者癌组织中ARID1 A?PIK3 CA?Ki-67蛋白表达明显异常,且与病变级别?临床分期密切相关,其中PIK3 CA蛋白阳性表达可明显增加复发率。     

Survivin和COX-2在皮肤基底细胞癌和鳞状细胞癌组织中的表达及相关性

目的了解皮肤基底细胞癌和皮肤鳞状细胞癌中Survivin和COX-2的表达情况及两者的关系。方法采用免疫组化法检测10例正常对照组、23例基底细胞癌、18例鳞状细胞癌组织中Survivin和COX-2的表达情况。结果 Survivin蛋白在正常组织中不表达,基底细胞癌和鳞状细胞癌中Survivin蛋白的表达率分别为60.87%和66.67%。COX-2在正常组织中的表达率为10%,基底细胞癌和鳞状细胞癌中COX-2的表达率分别为65.22%和66.67%,且明显高于其在正常组织中的表达率。Survivin的表达和COX-2的表达呈显著正相关(P0.05)。结论 Survivin蛋白和COX-2在皮肤基底细胞癌和皮肤鳞状细胞癌中高表达,两者呈正相关。     

表皮肿瘤中COX-2与P53的检测

目的了解表皮肿瘤组织环氧合酶-2(COX-2)与P53的表达情况。方法免疫组化法检测脂溢性角化病(SK)15例、Bowen’s病(BD)15例、基底细胞上皮瘤(BCE)20例、鳞癌(SCC)20例COX-2和P53的表达。结果所检测的各肿瘤组织标本均有COX-2的表达,分别为SCC95%,BD73.3%,SK46.6%,BCE68.0%,表达强度以SCC最为显著,周围正常组织未见表达。突变型P53在SCC(80.0%),BCE(75.0%),BD(33.3%)肿瘤组织的阳性率较高,而在SK(13.3%)中基本不表达。SCC和BCECOX-2表达阳性者其突变型P53表达的阳性率较COX-2表达阴性者高(P<0.05)。结论表皮肿瘤存在COX-2的过表达;P53的突变与COX-2的过表达有关,p53突变可能是通过上调COX-2水平发挥抗凋亡作用,从而促进SCC,BCE的形成和发展。     

皮肤鳞状细胞癌和基底细胞上皮瘤膜型基质金属蛋白酶-1、基质金属蛋白酶-2表达

目的 探讨皮肤鳞状细胞癌(简称鳞癌)和基底细胞上皮瘤(简称BCE)膜型基质金属蛋白酶-1(MT1-MMP)、基质金属蛋白酶-2(MMP-2)表达及其与临床病理特征的关系。方法 应用原位杂交和ABC免疫组化技术检测48例皮肤鳞癌和41例BCE手术切除标本中MT1-MMP、MMP-2表达。结果 鳞癌中MT1-MMP、MMP-2表达明显高于BCE(P<0.05),且二者的表达呈显著正相关(r=0.370,P<0.05)。MT1-MMP表达在高分化或伴有淋巴结转移的鳞癌中明显上调(P<0.05),而MMP-2表达增加仅见于伴有淋巴结转移的鳞癌(P<0.05)。鳞癌和BCE中MT1-MMP、MMP-2表达与患者性别、年龄、病程、发病部位、原发/转移病灶及BCE侵袭性无关(P>0.05)。结论 MT1-MMP、MMP-2表达上调与皮肤鳞癌的淋巴结转移有关。MT1-MMP、MMP-2表达水平不能区别BCE是否具有侵袭性。     

Lamin expression in normal human skin,actinic keratosis,squamous cell carcinoma and basal cell carcinoma

BACKGROUND: Aberrant expression patterns of nuclear lamins have been described in various types of cancer depending on the subtype of cancer, its aggressiveness, proliferative capacity and degree of differentiation. In general, the expression of A-type lamins (lamins A and C) has been correlated with a non-proliferating, differentiated state of cells and tissues. OBJECTIVES: To establish and compare the expression patterns of lamins in normal human skin, actinic keratosis (AK), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). METHODS: Expression patterns of the individual lamin subtypes were studied immunohistochemically. The proliferation capacity of the tumour cells was detected using a specific antibody to Ki-67, and was related to the A-type lamin expression patterns. RESULTS: In normal skin, lamin A was expressed in the suprabasal cell compartment of the epidermis, whereas the basal cells were mostly unstained. BCCs and SCCs stained positive in most cells, while the epidermis overlying BCC and SCC and the epidermis in AK stained homogeneously and strongly in the basal cells in addition to the suprabasal cells. Lamin C was expressed in some basal cells of normal epidermis while the suprabasal cells stained strongly positive. Both BCCs and SCCs stained strongly positive for lamin C, with the difference that in BCC the staining was predominantly present in nucleolar structures with occasional staining of the nuclear envelope. The epidermis overlying SCC showed strong positivity in the lamina of virtually all cells. The expression of lamin C in the basal cells of AK resembled the expression pattern seen in the epidermis overlying BCC, i.e. a nucleolar staining next to nuclear envelope staining. Lamin B1 and B2 were found in virtually all cells in normal epidermis, AK, BCC, SCC and the epidermis overlying cancer. The percentage of Ki-67-expressing cells was highest in BCC (45%), and gradually decreased via epidermis overlying BCC, AK, SCC, and epidermis overlying SCC, to normal skin (11%). Simultaneous expression of A-type lamins and Ki-67 occurred in approximately 50% of the proliferating (Ki-67 positive) cells in BCC and SCC. CONCLUSIONS: Significant changes occur in the expression patterns of A-type lamins in both premalignant and malignant lesions of the skin. The profound overlap of lamin A and Ki-67 staining patterns indicates that the proliferating tumour cells may obtain a certain degree of differentiation. Finally, lamin A expression in the basal cell layer of the apparently normal epidermis overlying BCC may suggest its involvement in the primary process.     

GLUT-1、Ki-67在皮肤肿瘤中的表达及意义

目的：探讨葡萄糖转运蛋白-1（GLUT-1）在脂溢性角化病（SK）、日光性角化病（AK）、Bowen病（BD）、鳞状细胞癌（SCC）中的表达及其与细胞增殖因子Ki-67之间的关系。方法：采用免疫组化法检测了95例不同皮肤肿瘤GLUT-1及Ki-67的表达。结果：GLUT-1及Ki-67在SK及正常皮肤都不表达,在AK、BD及SCC表达上调,并且二者的阳性表达强度间具有正相关性。结论：GLUT-1在恶性皮肤肿瘤中表达上调,与肿瘤的侵袭和转移有关。其表达强度可作为判断皮肤肿瘤恶性程度的检测指标,对诊断及鉴别诊断具有参考价值。     

Livin和Caspase-3在皮肤基底细胞癌和皮肤鳞状细胞癌组织中的表达及相关性分析

目的了解皮肤基底细胞癌和皮肤鳞状细胞癌组织中Livin和Caspase-3的表达情况及二者的关系。方法采用免疫组化法检测25例基底细胞癌、18例鳞状细胞癌组织中Livin和Caspase-3的表达情况。结果①Livin蛋白在正常皮肤组织中不表达,基底细胞癌和鳞状细胞癌组织中Livin蛋白的阳性表达率分别为64.00%和72.22%。②Caspase-3在正常皮肤组织中表达,且明显高于基底细胞癌和鳞状细胞癌组织中Caspase-3的表达。③Caspase-3的表达与Livin的表达呈显著负相关。结论Livin在基底细胞癌和鳞状细胞癌组织中高表达,Caspase-3蛋白在基底细胞癌和鳞状细胞癌组织中低表达,且与Livn的表达呈负相关,提示二者可能共同参与基底细胞癌和鳞状细胞癌发病过程。     

Apoptosis and cellular proliferation in human epidermal squamous cell neoplasia

We examined cell loss (apoptosis) and proliferation in a histopathological spectrum of epidermal squamous cell neoplasia, including 11 cases of solar keratosis (SK), 18 Bowen's diseases (BD) and 19 invasive squamous cell carcinomas (SCC). Apoptotic and proliferative cells were determined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) and by the detection of nuclear antigen Ki-67, respectively. Few apoptotic cells were observed in normal epidermis, while TUNEL index (TI; percentage of TUNEL-positive cells) was highest for SCCs, followed by BDs and SKs, in the order given. Although the mean Ki-67 index did not differ between SCCs and BDs. both disease types showed a significantly higher index than the SKs. Of SCCs, both TI and Ki-67 index values were significantly higher in poorly than in well differentiated carcinomas. TI was significantly higher in SCCs without P53 immunohistochemical expression than in SCCs with P53 expression, while TI and Ki-67 indices did not correlate with P53 expression in the SKs and BDs. These results suggest that apoptosis reflects not only cell loss, but also proliferative activity in the epidermal neoplastic lesions.     

Expression of bcl-2, p53 and Ki-67 in arsenical skin cancers

To investigate the regulation of apoptosis and proliferation in arsenic-induced skin cancers, we examined the expression of bcl-2. p53, and Ki-67 using immunohistochemical staining. Thirty patients with Bowen's disease (BD), ten with basal cell carcinoma (BCC), eight with squamous cell carcinoma (SCC) and eleven of perilesional normal skin (PLN) of the non-sun exposure sites from endemic area were examined. The results showed that: 1) bcl-2 was expressed in all of the BCC homogeneously, in none of the SCC, and in 12/30 of the BD focally or homogeneously; 2) p53 was expressed in all of the arsenical skin cancers with a labelling index of 75±14% of BD, 50±17% of BCC. 61±15% of SCC, and also in all of the perilesional normal skin with a labelling index of 55±24%; 3) Ki-67 was expressed in all of the skin cancers with labelling index of 58±17% of BD. 12±7% of BCC, 47±21% of SCC, and in 9/11 of PLN with a labelling index of 41±24%. Expression of bcl-2 in BCC or BD is related to the phenotype of germinative basal cell. The constant expression of bcl-2 i early dysplastic cells of BD and the earliest expression of P53 in the basal cells of perilesional normal skin indicate that the initial step of arsenic-induced carcinogenesis is from the basal germinative cells. There is no mutual relationship between bcl-2, p53 or Ki-67 expression in any type of the arsenical skin cancers, but there is a positive correlation between p53 and Ki-67 expression identified in perilesional normal skin. BD had the highest labelling index of p53 and Ki-67.