PTEN和Survivin在鳞状细胞癌中的表达

目的探讨抑癌蛋白PTEN和凋亡抑制因子Survivin在皮肤鳞状细胞癌中的表达及其意义。方法采用免疫组化SP法检测40例皮肤鳞状细胞癌和30例正常人皮肤中PTEN、Survivin的表达和分布。结果40例鳞状细胞癌标本中,PTEN表达下调(P<0.001),分化越差下调越明显(P<0.001)。Survivin表达增高(P<0.001)。PTEN和Survivin的表达呈显著负相关(P<0.001)。结论PTEN异常低表达和Survivin异常高表达可能与鳞状细胞癌的发病有关,PTEN表达异常的程度可能对判断预后有一定意义。     

鲍温病组织中PTEN和Survivin的检测

目的探讨抑癌蛋白PTEN和凋亡抑制因子Survivin在鲍温病发病中的作用。方法采用免疫组化SP法检测30例鲍温病组织和20例正常皮肤组织中PTEN和Survivin的表达。结果30例鲍温病组织中PTEN表达下调(P<0.001),Survivin的表达增高(P<0.001)。PTEN和Survivin的表达呈负相关(P<0.001)。结论PTEN异常低表达和Survivin异常高表达可能与鲍温病的发病有关。     

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.     

皮肤鳞状细胞癌和基底细胞癌组织中β-转化生长因子1及受体1表达

目的:观察皮肤鳞状细胞癌(SCC)和基底细胞癌(BCC)组织中β-转化生长因子1(TGF-β1)及其受体1(TβR-Ⅰ)表达与临床、组织病理特征的关系。方法:应用ABC免疫组化技术检测48例皮肤SCC和41例BCC手术切除标本中TGF-β1和TβR-Ⅰ的表达。结果:SCC中TGF-β1、TβR-Ⅰ表达明显高于BCC(P<0.05);高分化SCC中TβR-Ⅰ表达明显上调(P<0.05),但TGF-β1表达与肿瘤分化程度无关(P>0.05)。SCC和BCC中TGF-β1与TβR-Ⅰ的表达呈显著正相关(r=0.739,P<0.001;r=0.716,P<0.001),但其与患者性别、年龄、病程、发病部位、病灶、淋巴结转移及BCC侵袭性无关(P>0.05)。结论:TGF-β1表达与肿瘤分化程度、侵袭性及淋巴结转移无关。     

PTEN和Endoglin在皮肤鳞状细胞癌中的表达

目的探讨PTEN在皮肤鳞状细胞癌的发生和转移中的作用,以及PTEN和Endoglin对皮肤鳞状细胞癌新生血管的作用。方法采用免疫组化EliVision法染色,对52例皮肤鳞状细胞癌、10例正常皮肤标本进行PTEN和Endoglin标记,观察并分析表达情况。结果正常对照组PTEN蛋白的阳性表达率为100.00%,皮肤鳞状细胞癌组为48.08%,两组比较,差异有统计学意义(P<0.01),且染色评分也随之降低(P<0.01)。PTEN蛋白在高分化及中-低分化皮肤鳞状细胞癌组中的阳性率分别为78.57%和36.84%,差异有统计学意义(P<0.05)。随着淋巴结转移的出现,PTEN的阳性率显著下降,由58.54%降至9.09%,差异有显著的统计学意义(P<0.01)。Endoglin标记的微血管密度(Endoglin-MVD)在皮肤鳞状细胞癌组(30.56±6.41)和正常对照组(3.00±1.63)比较,在中-低分化皮肤鳞状细胞癌组(31.95±5.74)和高分化组(26.79±6.83)比较,差异均有统计学意义(P均<0.01),在淋巴结转移组(34.73±4.50)和无转移组(29.44±6.43)比较,差异也有统计学意义(P<0.05)。PTEN阴性表达的Endoglin-MVD为33.63±5.09,PTEN阳性表达的Endoglin-MVD为27.24±6.11,两者呈负相关。结论 PTEN蛋白的表达下降参与了皮肤鳞状细胞癌的发生、恶性进展及转移;PTEN与Endoglin-MVD的表达存在相关性,影响皮肤鳞状细胞癌新生血管的生成。     

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。     

HIF-1α和Glut-1在皮肤鳞状细胞癌和基底细胞癌中的表达

目的:检测缺氧诱导因子-1α(HIF-1α)、葡萄糖转运蛋白1(Glut-1)在皮肤鳞状细胞癌(SCC)、基底细胞癌(BCC)组织中的表达.方法:采用免疫组织化学方法检测74例SCC、71例BCC及30例正常皮肤组织中HIF-1α和Glut-1的表达.结果:SCC中HIF-1α和Glut-1蛋白阳性表达率分别为68.92%和82.43%.BCC中HIF-1α和Glut-1蛋白阳性表达率分别为61.97%和56.34%.均高于正常皮肤组织0%和6.67%(P<0.05).HIF-1α和Glut-1的表达与SCC和BCC患者的年龄、性别、分化程度无关,但与SCC淋巴结转移密切相关(P<0.05).结论:HIF-1α和Glut-1的过度表达可能与SCC和BCC的发生和转移有关.     

表皮生长因子受体和PTEN蛋白在尖锐湿疣皮损中的检测及意义

目的探讨表皮生长因子受体(EGFR)和PTEN蛋白在尖锐湿疣、正常皮肤、皮肤恶性肿瘤中的分布及在尖锐湿疣发病中的作用及意义。方法采用免疫组化SP法分别检测EGFR和PTEN蛋白在正常皮肤、尖锐湿疣、基底细胞癌(BCC)、鳞状细胞癌(SCC)中的分布。比较二者在三组标本中的分布差异。结果EGFR在尖锐湿疣组织除角质层外的表皮全层细胞均为强阳性,在正常皮肤多为中等阳性,且多分布在基底层和棘层下部。在BCC和SCC中,EGFR强阳性(χ2=37.07,P<0.01)。PTEN蛋白主要分布在正常皮肤表皮层的棘层上方,在尖锐湿疣全层的细胞膜和细胞浆中呈中等阳性;在BCC和SCC中,PTEN蛋白减弱或缺失,角珠中PTEN蛋白多呈强阳性(χ2=59.191,P<0.01)。结论EG-FR和PTEN蛋白在尖锐湿疣,BCC,SCC及正常皮肤组织中,其分布的范围和阳性的强度有所不同,检测EGFR和PTEN蛋白可以作为判断尖锐湿疣转归的一种方法。     

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。     

Fas/FasL在基底细胞癌和鳞状细胞癌中的表达

目的:检测Fas/FasL在基底细胞癌(BCC)和鳞状细胞癌(SCC)中的表达.方法:采用SABC技术分别检测Fas/FasL在BCC、SCC及正常人对照皮肤中的表达.结果:Fas/FasL在BCC组不表达或弱表达,较正常人组无显著差异(P＞0.05);SCC组Fas和FasL的表达均高于对照皮肤(P＜0.05和＜0.01).Fasl染色主要集中于肿瘤细胞,弥漫染色,在肿瘤团块边缘表达更强;Fas在角珠处表达较强.结论:FasL在基底细胞癌不表达或弱表达,表明BCC侵袭扩散能力低,而在鳞状细胞癌中高表达可能与肿瘤的侵袭扩散能力高有关.     

Survivin和Ki-67在皮肤鳞癌和基底细胞上皮瘤的表达及相关性分析

目的观察Survivin和Ki-67在皮肤鳞癌(SCC)及基底细胞上皮瘤(BCE)的表达,并探讨其意义。方法采用免疫组化法检测15例皮肤SCC,20例BCE中Survivin和Ki-67的表达情况,并以16份整形手术切除的正常组织作为对照。结果Survivin在皮肤SCC和BCE中的阳性表达率显著高于正常对照组,且在皮肤SCC的阳性表达率也显著高于BCE,差异均有统计学意义(P均<0.05)。Ki-67在皮肤SCC和BCE中的阳性表达也显著高于正常对照组(P<0.05),但在皮肤SCC和BCE组织中的表达比较,差异无统计学意义(P>0.05)。皮肤SCC和BCE组织中Survivin和Ki-67的阳性细胞表达呈正相关(r=0.77,P<0.05)。结论Survivin与Ki-67在皮肤SCC和BCE组织中的表达均升高,且呈正相关,提示两基因有可能共同参与肿瘤的发生和发展。     

P62和Caspase-8在皮肤基底细胞癌组织中的表达

目的：比较基底细胞癌（BCC）及正常皮肤组织中Caspase-8和P62的表达水平,探讨Casepase-8和P62在BCC发病中的作用。方法：利用免疫组织化学染色法检测45例BCC病理组织及10例正常皮肤上皮组织中Caspase-8和P62蛋白的表达。结果：44%(20/45) BCC和90%(9/10)正常皮肤组织中Caspase-8阳性表达,两组Caspase-8阳性率差异有统计学意义（Z=-2.711,P<0.01）; 87%（39/45）BCC中和40%(4/10)正常皮肤组织中P62呈阳性,两组P62阳性率差异有统计学意义（Z=-2.951,P<0.01）。Caspase-8和 P62在BCC中的表达水平呈现负相关（r= -0.322,P<0.05）。结论：Caspase-8 和P62在BCC组织中低表达,可能与BCC的发病机制有关。     

P16 is overexpressed in cutaneous carcinomas located on sun-exposed areas

BACKGROUND: Recently, an increased expression of P16, a cell cycle regulatory tumor suppressor protein, has been demonstrated in cervical squamous neoplasms as a marker of malignancy. In contrast, studies performed in skin carcinomas led to contradictory results. OBJECTIVES: Our first aim was to evaluate P16 expression in different types of non-melanoma skin cancers compared with normal skin and benign tumors. The second aim was to evaluate the relationship between P16 expression and the location of skin tumors (i.e. exposed versus non exposed sites). Finally, we also studied Ki67 expression in skin carcinomas and control biopsies. METHODS: Skin biopsy specimens with typical histologic features of squamous cell carcinoma (SCC; n = 30), Bowen's disease (BD; n = 17), basal cell carcinoma (BCC; n = 10), seborrheic keratosis (SK; n = 10) and normal human skin (NHS; n = 9) were obtained from 76 patients seen at our institution between 2001 and 2003. In all cases, P16 and Ki67 expression were evaluated by immunohistochemistry and image analysis. RESULTS: P16 overexpression was observed in 58% of cutaneous carcinomas (SCC: 60%; BD: 58%; BCC: 50%) versus 0% of SK or NHS (0%) (p = 0.006). Ki67 expression in over 5% of tumour cells was observed in 69% of cutaneous carcinomas (SCC: 54%; BD: 76%; BCC: 80%) versus 16% in the group including SK (30%) and NHS (0%) (p = 0.04). Overexpression of P16 was associated with a high rate of Ki67 positive tumour cells in 23/57 malignant skin tumors (40%). Both P16 was associated and Ki-67 were negative in 7/57 cases (12%). Sixty-eight percent of tumors located on sun-exposed areas versus 23% of those located on non sun-exposed areas overexpressed P16 (p = 0.02). CONCLUSION: Our study demonstrated that the expression of P16 and Ki67 is associated with skin carcinomas. No difference was observed according to histological types of carcinomas, suggesting that P16 and Ki67 expression did not correlate with the degree of proliferation and malignancy. Within cutaneous carcinoma specimens, P16 overexpression was significantly associated with the location on sun-exposed areas, suggesting a possible induction of P16 overexpression by UV radiation.     

Downregulation of the inhibitor of apoptosis protein survivin in keratinocytes and endothelial cells in psoriasis skin following infliximab therapy

BACKGROUND: Survivin, an inhibitor of apoptosis protein (IAP), has been implicated in endothelial cell stability, through inhibition of apoptosis and in cell proliferation. OBJECTIVES: To evaluate the effect of antitumour necrosis factor (TNF)-alpha therapy on survivin expression in psoriasis skin at 0, 2 and 12 weeks after infliximab therapy. METHODS: Skin biopsies were obtained from 16 patients; 11 also had arthritis with active skin/joint disease. Clinical scores [Psoriasis Area and Severity Index (PASI), involved body surface area (BSA), Disease Activity Score (DAS28) and Health Assessment Questionnaire] were recorded. Inflammatory infiltration and survivin protein expression were examined and graded by immunohistochemical staining, and mRNA levels were determined by real-time polymerase chain reaction. RESULTS: Survivin mRNA and protein were demonstrated in all baseline lesional biopsies. Survivin mRNA and protein expression was significantly greater in lesional compared with nonlesional baseline skin (P < 0.05). Differential cellular localization of survivin was demonstrated with cytoplasmic survivin protein expression localized to the perivascular/endothelial regions and strong nuclear staining localized in the basal layer of the epidermis. Infliximab produced a dramatic clinical response in skin and joints (P < 0.05), paralleled by significant reduction in the inflammatory infiltrate and survivin protein expression (P < 0.05) which was reflected at the mRNA level where expression was significantly reduced by week 12 (P < 0.01). Survivin protein levels before and after treatment significantly correlated with PASI (r = 0.478, P < 0.05) and BSA scores (r = 0.528, P < 0.024). PASI strongly correlated with BSA (r = 0.949, P < 0.0001) and DAS28 (r = 0.717, P < 0.002) scores. CONCLUSIONS: Survivin correlates with disease activity in patients with psoriasis and is significantly downregulated following anti-TNF-alpha treatment. Understanding the role of IAPs in cell survival/antiapoptosis and proliferation mechanisms may provide important insights into downstream therapeutic targeting in inflammation.     

热休克蛋白10、60在皮肤鳞状细胞癌、基底细胞癌、日光性角化病中的表达

目的 探讨热休克蛋白（HSP）10、60在皮肤鳞状细胞癌（SCC）、基底细胞癌（BCC）和日光性角化病（AK）中的表达水平。方法 采用免疫组化EnVision两步法测定HSP10、60在皮肤SCC、BCC、AK中的阳性表达水平,并与正常组对照。结果 与对照组比较,HSP10组只有BCC组的阳性表达高于正常组（Z = 3.24,P < 0.01）,AK组（Z = 0.74,P > 0.05）和SCC组（Z = 0.52,P > 0.05）与对照组比较差异无统计学意义;HSP10组中AK与BCC,AK与SCC的差异有统计学意义（P < 0.05）,但SCC与BCC组间差异无统计学意义（P > 0.05）。HSP60组三组的阳性表达均高于正常组,其中AK（Z = -2.90,P < 0.01）、BCC（Z = -2.15,P < 0.05）、SCC（Z = -2.78,P < 0.01）;三组间两两比较结果为AK = SCC > BCC（P < 0.05）。结论 HSP60的高表达可能与鳞状细胞癌、日光性角化病的生物行为有关。     

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。