皮肤鳞状细胞癌组织Syndecan-1和乙酰肝素酶表达及临床意义

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目的近期研究显示,Syndecan-1和乙酰肝素酶(heparanase,HPA-1)可能参与多种恶性肿瘤的侵袭和转移,但关于两者与皮肤鳞状细胞癌(cutaneous squamous cell carcinoma,CSCC)的关系较少报道。本研究旨在探讨Syndecan-1和HPA-1在CSCC组织中的表达及其与临床病理特征的关系。方法应用免疫组化方法、蛋白质印迹法和实时荧光定量PCR技术检测2009-09-01-2014-03-31潍坊市人民医院皮肤科93例CSCC及30名正常表皮中Syndecan-1和HPA-1蛋白及mRNA的表达水平。结果正常表皮、原位鳞癌、高分化鳞癌、中分化鳞癌和低分化鳞癌中Syndecan-1强阳性率分别为70.00%(21/30)、52.28%(11/21)、37.04%(10/27)、23.33%(7/30)和6.67%(1/15),CSCC Syndecan-1表达强度显著低于正常表皮对照组,χ2=13.17,P<0.01;在不同肿瘤厚度和分化程度的鳞癌中,SDC1表达强度随肿瘤厚度的增加(χ2=11.66,P<0.01)和分化程度的降低(χ2=12.51,P<0.01)而有下降趋势;CSCC患者中伴淋巴结转移组Syndecan-1表达强度显著低于无淋巴结转移组,χ2=5.78,P<0.05。CSCC组织Syndecan-1mRNA和蛋白表达水平显著低于正常对照组,且随着组织学分级的降低而依次降低(rs值分别为0.829和0.644,均P<0.001)。正常表皮、原位鳞癌、高分化鳞癌、中分化鳞癌和低分化鳞癌中HPA-1阳性率分别为3.33%(1/30)、38.10%(8/21)、62.96%(15/27)、66.67%(20/30)和86.67%(13/15),CSCC中HPA-1表达强度显著高于对照组,χ2=29.52,P<0.01。在不同肿瘤厚度和分化程度的鳞癌中,HPA-1表达强度随肿瘤厚度的增加(χ2=4.70,P<0.05)和分化程度的降低(χ2=9.15,P<0.05)而有增加的趋势,CSCC患者中伴淋巴转移组HPA-1表达强度(80.95%)显著高于无淋巴结转移组(54.17%),χ2=4.87,P<0.05。CSCC组织HPA-1mRNA和蛋白表达水平显著高于正常对照组,且随着组织学分级的降低而依次升高(rs值分别为-0.793和-0.718,均P<0.001)。CSCC中Syndecan-1与HPA-1表达呈负相关,rs=-0.473,P<0.01。结论 Syndecan-1表达降低与HPA-1表达增强可能促进CSCC的侵袭和转移。 Purpose Recent studies have shown that Syndecan-1 and heparanase (HPA-1) may be involved in the invasion and metastasis of many malignant tumors. However, both of them are related to the expression of cutaneous squamous cell carcinoma (CSCC) Less relationship reported. This study aimed to investigate the expression of Syndecan-1 and HPA-1 in CSCC and its relationship with clinicopathological features. Methods The expression of Syndecan-1 and HPA-1 in 93 CSCC and 30 normal epidermis from Department of Dermatology, Weifang People’s Hospital, 2009-09-01-2014-03-31 By immunohistochemistry, Western blot and real-time fluorescence quantitative PCR Protein and mRNA expression levels. Results The positive rates of Syndecan-1 in normal epidermis, in situ squamous cell carcinoma, well differentiated squamous cell carcinoma, moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma were 70.00% (21/30), 52.28% (11/21), 37.04% (10/27), 23.33% (7/30) and 6.67% (1/15) respectively. The expression of Syndecan-1 in CSCC was significantly lower than that in normal epidermis control group (χ2 = 13.17, P <0.01) (Χ2 = 11.66, P <0.01) and the degree of differentiation decreased (χ2 = 12.51, P <0.01), while the expression of SDC1 in the squamous cell carcinoma of the degree of SCC decreased with the increase of the thickness of the tumor. Syndecan -1 expression was significantly lower than the group without lymph node metastasis, χ2 = 5.78, P <0.05. The expression of Syndecan-1 mRNA and protein in CSCC was significantly lower than that in the normal control group, and decreased with the decreasing of histological grade (rs 0.829 and 0.644 respectively, P 0.001). The positive rates of HPA-1 in normal epidermis, squamous cell carcinoma in situ, well differentiated squamous cell carcinoma, well differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma were 3.33% (1/30), 38.10% (8/21), 62.96% (15) /27),66.67% (20/30) and 86.67% (13/15) respectively. The expression of HPA-1 in CSCC was significantly higher than that in control group (χ2 = 29.52, P <0.01). In squamous cell carcinoma with different thickness and degree of differentiation, the expression of HPA-1 increased with the increase of tumor thickness (χ2 = 4.70, P <0.05) and differentiation (χ2 = 9.15, P <0.05) The expression of HPA-1 in CSCC patients with lymph node metastasis (80.95%) was significantly higher than that without lymph node metastasis (54.17%) (χ2 = 4.87, P <0.05). The expression of HPA-1mRNA and protein in CSCC were significantly higher than those in normal control group, and increased with the decrease of histological grade (rs = -0.793 and -0.718, respectively, P <0.001). Syndecan-1 and HPA-1 expression in CSCC was negatively correlated, rs = -0.473, P <0.01. Conclusion The decreased expression of Syndecan-1 and the increased expression of HPA-1 may promote the invasion and metastasis of CSCC.
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