COX-2和Ki-67在尖锐湿疣组织中的表达及意义

目的探讨尖锐湿疣(CA)组织中环氧化酶-2(COX-2)和增殖指标K i-67的表达及意义。方法用免疫组化SP法分别检测COX-2蛋白和K i-67蛋白在38例CA组织和15例正常上皮组织中的表达。结果COX-2蛋白在CA组和正常皮肤组的阳性率分别为68.4%(26/38)和0,表达强度分别为3.921±0.254和0.883±0.088,二者在阳性率及表达强度上差异均有显著性(P均<0.01);K i-67蛋白在CA组和正常皮肤组的阳性率分别为84.2%(32/38)和60.0%(9/15),表达强度分别为0.234±0.021和0.05±0.006,二者阳性率差异无显著性(P>0.05),但表达强度差异有显著性(P<0.05);COX-2蛋白和K i-67蛋白之间的阳性表达呈正相关(r=0.497,P<0.01)。结论COX-2在CA发生、发展中起一定作用,与细胞的增殖有关。     

COX-2和Ki67在鲍恩病皮损中的表达

目的研究COX-2和Ki67在鲍恩病皮损中的表达情况,并探讨两者之间的关系。方法应用免疫组化SP染色法对27例鲍恩病患者皮损及15份正常皮肤组织进行COX-2和Ki67染色。结果 COX-2与Ki67在正常皮肤组织中表达非常低,而在鲍恩病皮损中染色强度显著增高(P0.05)。COX-2与Ki67在鲍恩病皮损中的表达水平呈显著正相关(r=0.451,P0.05)。结论 COX-2与鲍恩病的发生密切相关,过度表达的COX-2蛋白可能参与肿瘤细胞的增生过程。     

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。     

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。     

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。     

Hedgehog信号通路在皮肤鳞状细胞癌中表达

目的 探讨Hedgehog信号转导通路在皮肤鳞状细胞癌中的激活水平及抑制该信号通路对鳞状细胞癌增殖的影响。方法 免疫组化和原位杂交方法检测鳞状细胞癌皮损及正常皮肤中Hedgehog信号通路靶基因Ptch-1和Gli-1的表达水平和分布。MTT和BrdU掺入的方法,检测Hedgehog信号转导通路特异性抑制剂环巴胺对Tca鳞状细胞癌细胞生长和增殖的影响。结果 在鳞状细胞癌皮损中Ptch-1表达高于正常人皮肤（免疫组化χ2 = 5.656,P < 0.05;原位杂交χ2 = 6.787,P < 0.01）,Gli-1表达也高于正常人皮肤（免疫组化χ2 = 6.732,P < 0.01;原位杂交χ2 = 9.600,P < 0.01）,阳性颗粒主要分布于鳞状细胞癌细胞胞质中。MTT和BrdU掺入实验均显示环巴胺可以抑制Tca鳞状细胞癌细胞的生长和增殖。结论 鳞状细胞癌皮损中Hedgehog信号转导通路处于激活状态,抑制该通路可能对鳞状细胞癌起到一定的治疗作用。     

p53、Gadd45α蛋白在皮肤鳞状细胞癌、基底细胞癌中的表达

目的:检测p53和Gadd45α蛋白在皮肤鳞状细胞癌和基底细胞癌组织中的表达.方法:应用免疫组化法对30例皮肤鳞状细胞癌和25例基底细胞癌组织中的p53和Gadd45α蛋白表达进行检测.结果:p53蛋白在皮肤鳞状细胞癌和基底细胞癌组织中的表达阳性率分别为56.67%、48%,与正常皮肤组织比较差异均有显著性(P=0.006;0.025);Gadd45α在皮肤鳞状细胞癌和基底细胞癌中表达分别为43.33%、52%,均高于正常皮肤组织的表达(P=0.031;0.010).高分化皮肤鳞状细胞癌组阳性表达率为75%,高于中低分化组的22.22%(P=0.008).结论:皮肤鳞状细胞癌和基底细胞癌组织中p53、Gadd45α异常表达可能参与了发病过程.     

皮肤鳞状细胞癌组织中E-钙黏素和α-SMA的表达

目的:检测皮肤鳞状细胞癌组织中E-钙黏素和α-SMA的表达.方法:用免疫组化法检测30例皮肤鳞状细胞癌组织中E-钙黏素和α-SMA蛋白的表达.结果:与癌旁及正常皮肤组织相比,E-钙黏素在皮肤鳞状细胞癌中表达减弱或缺失(P<0.05),中低分化与高分化癌组织组间比较差异有显著性(P<0.05);皮肤鳞状细胞癌癌巢周边组织...     

Jagged1蛋白在银屑病、基底细胞癌及皮肤鳞状细胞癌中的表达

目的探讨Jagged1蛋白在银屑病、基底细胞癌及皮肤鳞状细胞癌中的表达及意义。方法采用免疫组化Envision法检测Jagged1蛋白在银屑病、基底细胞癌及皮肤鳞状细胞癌皮损中的表达。结果 Jagged1蛋白在寻常性银屑病患者皮损中呈阴性表达,在基底细胞癌及皮肤鳞状细胞癌中的表达较正常人皮肤增强,差异有统计学意义(P<0.01);Jagged1蛋白在基底细胞癌及皮肤鳞状细胞癌中的表达较银屑病增强,差异有统计学意义(P<0.05)。结论 Jagged1蛋白在银屑病发病机制中与角质形成细胞异常增生及真皮乳头血管增生等组织病理变化可能不相关,提示此蛋白可能与皮肤恶性肿瘤的异常增生有关。     

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。     

Cyclooxygenase-2 expression and angiogenesis in squamous cell carcinoma of the skin and its precursors: a paired immunohistochemical study of 35 cases

BACKGROUND: Cyclooxygenase (COX)-2 expression and tumour-induced angiogenesis appear to be increased in squamous cell carcinoma (SCC) of the skin. In other cancers, COX-2 is a pro-angiogenic factor. The association between angiogenesis and COX-2 has not been studied in skin cancer. OBJECTIVES: To assess the onset of increased COX-2 expression and angiogenesis in the multistage carcinogenesis of SCC as well as the correlation between those two parameters. PATIENTS/METHODS: We performed a retrospective paired immunohistochemical analysis of normal skin, actinic keratosis (AK), Bowen's disease (BD) and SCC among 35 individuals. Specimens were considered COX-2 immunopositive when 5% or more of the tumour cells showed clear evidence of immunostaining. To quantify active angiogenesis, we used a Ki-67-CD34 double-labelling immunohistochemical stain and calculated the fraction of proliferating endothelial cells. The Chalkley method was used to determine the microvessel density. To detect hypoxia, a carboanhydrase IX immunostain was used. RESULTS: Compared with normal epidermis (0%), AK (31%), BD (22%) and SCC (40%) were significantly more likely to be COX-2 immunopositive (P < 0.01). The fraction of proliferating endothelial cells and the Chalkley scores paralleled multistage carcinogenesis (P < 0.05 between different stages). COX-2 immunopositivity was fairly correlated with hypoxia and higher proliferating endothelial cell fractions but not with Chalkley counts. CONCLUSIONS: Induction of COX-2 expression and angiogenesis are both early events in the development of SCC. In addition to ultraviolet light, hypoxia and COX-2 may be involved in skin tumour angiogenesis.     

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。     

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.     

CCL18在恶性黑素瘤中的表达及其与血管内皮生长因子、Ki67表达的相关性研究

目的：探讨趋化因子配体18（CCL18）在恶性黑素瘤（恶黑）组织中的表达和临床意义,与血管内皮生长因子（VEGF）、Ki67表达的相关性。方法用免疫组化方法检测58例恶黑石蜡标本中CCL18、VEGF及细胞增殖核抗原Ki67的表达,同时检测20例色素痣石蜡标本中CCL18的表达水平。对CCL18的表达与恶黑临床病理及VEGF、Ki67的表达进行相关性分析。用免疫荧光方法验证CCL18在恶黑组织中的表达。结果 CCL18在恶黑组阳性率为84.48%（49/58）,而在色素痣组均无表达,差异有统计学意义（χ2=45.46,P<0.01）。CCL18在恶黑的表达与肿瘤Clark分级、Breslow厚度呈正相关（rs值分别为0.609、0.644,均P<0.01）;在有无溃疡以及有无淋巴结转移组间差异有统计学意义（均P<0.05）。CCL18的表达在不同性别、年龄、肢端/非肢端恶黑患者组间差异无统计学意义（均P>0.05）。恶黑中CCL18阳性表达水平与VEGF表达水平呈正相关（rs=0.727,P<0.05）,与Ki67表达水平无相关（P>0.05）。免疫荧光显示,恶黑组织中肿瘤细胞胞质表达CCL18。结论 CCL18在恶黑组织中高表达,与肿瘤侵袭、转移有一定关系。     

p73蛋白在正常人皮肤和表皮肿瘤中的表达

目的 探讨p73蛋白在正常人皮肤和不同表皮肿瘤皮损中的表达及意义。方法 应用免疫组化方法检测19例脂溢性角化病、16例基底细胞癌、11例Bowen病、5例鳞状细胞癌及10例正常人皮肤p73、p53、Ki67的表达。结果 在正常人表皮基底层、毛囊外毛根鞘最外层基底样细胞和皮脂腺生发细胞有p73的表达;在基底细胞癌和脂溢性角化病的基底样细胞、Bowen病中异形性明显的瘤细胞p73呈高表达,鳞状细胞癌和脂溢性角化病中的鳞状细胞呈弱阳性或不表达。脂溢性角化病、Bowen病、基底细胞癌、鳞状细胞癌之间p73蛋白表达差异有统计学意义(H=12.71,P<0.01),其中基底细胞癌的表达最强。Ki67在皮肤肿瘤之间差异也有统计学意义(H=14.12,P<0.01),但p53差异无统计学意义(H=2.058,P>0.05)。在各组样本中,p73的表达与p53、Ki67无显著相关性(P>0.05)。结论 p73蛋白可能在皮肤分化中起重要作用。     

环氧合酶-2和血管内皮生长因子mRNA在皮肤鳞状细胞癌组织中的表达

目的 探讨环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)mRNA在皮肤鳞状细胞癌(SCC)和正常人皮肤组织中的表达以及它们之间相互关系。方法 应用逆转录-聚合酶链反应(RT-PCR)方法,检测24例SCC和10例正常人皮肤组织中COX-2和VEGF mRNA的表达。结果 RT-PCR结果显示,在正常人皮肤组织中COX-2和VEGF mRNA呈较弱表达或无表达,吸光度平均值分别为(0.01±0.01)和(0.02±0.02);有79.2%(19/24)SCC组织中COX-2 mRNA表达水平增高,平均值为(0.56±0.48),与正常皮肤组织比较差异有统计学意义(P<0.05);VEGF mRNA在SCC组织中全部高表达(24/ 24,100%),平均值为(0.66±0.35),与正常人皮肤组织比较差异有统计学意义(P<0.05)。经相关性分析两者之间的表达呈明显正相关(r=0.86)。结论 COX-2可能与SCC血管形成有关,且其作用可能通过上调VEGF通道来发挥作用。     

环氧合酶-2在皮肤肿瘤组织中的表达及其临床意义

目的　探讨环氧合酶 2 (COX 2 )在皮肤肿瘤组织中的表达及其临床意义。方法　应用免疫组织化学方法分别检测 82例皮肤肿瘤组织 ( 2 1例Bowen病、2 6例基底细胞癌、3 5例鳞状细胞癌 )和 10例正常皮肤组织中COX 2的表达。结果　皮肤肿瘤组织中COX 2阳性表达率为 76.83 % ,显著高于正常皮肤组织的 10 .0 0 % ( χ2 =15 .78,P <0 .0 1) ;COX 2主要表达于肿瘤细胞胞浆与核周 ;鳞状细胞癌的阳性表达与肿瘤分期无明显相关 ( χ2 =0 .70 ,P >0 .0 5 )。结论　COX 2的高表达可能与皮肤肿瘤的发生有关     

Overexpression of phosphorylated-STAT3 correlated with the invasion and metastasis of cutaneous squamous cell carcinoma

In order to evaluate the possible effects of STAT3 phosphorylation and expression of E-cadherin on metastasis of some human epidermal non-melanoma cutaneous tumors, the expression of phosphorylated STAT3 (p-STAT3) and E-cadherin were analyzed by immunohistochemistry staining in formalin-fixed, paraffin-embedded tissue sections of human cutaneous squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and seborrhoeic keratosis (SK). An immunohistochemistry staining technique was employed to measure the expression of p-STAT3 and E-cadherin protein in 30 cases of cutaneous SCC, 20 cases of BCC, 20 cases of SK, and 20 specimens of normal skin. The results were as follows: 1) p-STAT3 protein was abnormally increased in SCC as compared to normal skin and SK (p<0.001). Expression of p-STAT3 in SCC was also significantly higher than in BCC (p<0.05). 2) Expression of p-STAT3 was higher in poorly-differentiated SCC than in well-differentiated ones (p<0.05). The positive rate of the expression of p-STAT3 correlated well with the depth of tumor invasion and with metastasis (p<0.05), but there was no correlation between the positive rate and tumor size. 3) E-cadherin was strongly expressed on the cell membranes of normal skin and SK, especially on basal cells. E-cadherin was weakly expressed on cell membranes of SCC and BCC (p<0.001), whereas its expression was significantly lower in SCC than in BCC (p<0.05). In SCC, the intensity of E-cadherin expression was correlated with the extent of tumor differentiation, but there was no correlation between the expression intensity and the depth of tumor invasion or tumor size. 4) There was a negative correlation between the expression intensity of p-STAT3 and E-cadherin in SCC (rs=-0.372, p<0.05). We concluded that the overexpression of p-STAT3 may have an important role in the development of epidermal tumors. Abnormal activation of STAT3 may be related to metastasis potential in SCC and the simultaneous detection of p-STAT3 and E-cadherin may contribute to predicating the prognosis in SCC.