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成纤维细胞激活蛋白,整合素β1在皮肤鳞状细胞癌中的表达
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摘要
目的本研究检测成纤维细胞激活蛋白和整合素β1在皮肤鳞状细胞癌组织切片和正常皮肤切片中的表达情况,比较两种蛋白表达与皮肤鳞状细胞癌病理特征的关系,分析其表达之间的相关性,初步探讨成纤维细胞激活蛋白和整合素β1在皮肤鳞状细胞癌发生发展中的作用。
     材料和方法
     收集郑州大学第一附属医院整形外科自2006年~2008年确诊存档的皮肤鳞状细胞癌石蜡固定包埋的46例病理标本。病变部位来自头皮、面部、背部、四肢。所有患者术前均有详细的病例记录,未接受放射,激光,免疫等抗肿瘤治疗。男性20例,女性26例,年龄26~92岁(平均55.2岁)。皮肤鳞状细胞癌病理学分级:高分化、中分化、低分化。20例正常对照皮肤取自整形外科全厚皮片移植剩余皮片和美容手术切除皮肤。采用免疫组织化学方法进行实验。应用SPSS13.0统计软件进行统计学分析,P<0.05为有统计学意义。
     结果
     1.成纤维细胞激活蛋白在正常皮肤组织中无明显阳性表达。在皮肤鳞状细胞癌中成纤维细胞激活蛋白可见胞膜或胞质内呈明显棕黄色颗粒,阳性反应产物主要分布于肿瘤间质成纤维细胞的胞膜或胞质内。阳性表达率为87%。高分化鳞癌与中分化鳞癌比较差异无统计学意义(P>0.05),中分化鳞癌与低分化鳞癌(P<0.05),高分化鳞癌与低分化鳞癌比较差异有统计学意义(P<0.05)
     2.整合素β1在正常皮肤组织中呈现表面均质性高表达,阳性染色主要定位在细胞膜表面,胞质有少量表达。在皮肤鳞状细胞癌的细胞膜中,肿瘤细胞及肿瘤间质细胞中均有表达。阳性表达率为52%。在高分化鳞癌中呈高表达或接近高表达,在中低分化鳞癌细胞及间质中表达降低甚至消失。高中分化鳞癌比较差异有统计学意义(P<0.05),高低分化鳞癌比较差异有统计学意义(P<0.05),中低分化鳞癌比较无统计学意义(P>0.05)
     3.成纤维细胞激活蛋白的阳性表达与整合素β1的异常表达有关。二者的表达差异有统计学意义(P<0.05)。随成纤维细胞激活蛋白的表达加强,整合素β1表达减弱。
     结论
     1.成纤维细胞激活蛋白在皮肤鳞状细胞癌中表达而在正常皮肤中不表达,且成纤维细胞激活蛋白随皮肤鳞状细胞癌恶性程度的增高表达增强,提示成纤维细胞激活蛋白表达水平与肿瘤的恶性程度相关。
     2.整合素β1在正常皮肤中呈均质表达,在皮肤鳞状细胞癌中表达率较正常皮肤阳性率降低,且整合素β1随皮肤鳞状细胞癌恶性程度的增高表达减弱。提示整合素β1的表达与肿瘤恶性程度呈负相关。
     3.成纤维细胞激活蛋白表达与整合素β1表达异常,呈负相关,提示成纤维细胞激活蛋白的过表达可伴有整合素β1表达减弱,提示两者可能有共同的调节机制。
     4.研究成纤维细胞激活蛋白与整合素β1在皮肤鳞状细胞癌间质中的表达,有望使其成为皮肤鳞状细胞癌治疗的新靶点。
Objective
     This study examined the expression of Fibroblast activation protein (FAP) and Integrinβ1 in the tissue sections of skin squamous cell carcinoma patients'lesions and normal skin,to investigate the relationship between the expression and pathological features of skin squamous cell carcinoma.With the evaluate of the correlation between these two enzymes, try to find out their role in the development and metastasis of skin squamous cell carcinoma.
     Materials and methods:
     The 46 cases of skin squamous cell carcinoma tissues were obtained from the patients under plastic surgery in the Firsit Affiliated Hospital of Zhengzhou University from 2006 to 2008.The tissues were collected from the scalpe, face, back and perineum. All the tissues were required to accord with the principles:particulaer cases history and therapy out of radiation, laser, or immunity. There were 20 males and 26 females.The age of patients range from 26 to 92 years old (average 55.2years old).Skin squamous cell carcinoma perineum classification:well-differentiated, moderately differentiated, poorly differentiated. The 20 cases of normal skin tissues were residual skin tissues, collected from the operation of skin transplantation and cosmetic surgery. The experimental using immunohistochemical staining method to reflect the positivity of skin FAP and integrinβ1 in 46 cases of skin squamous cell carcinoma. The statistical analyses were performed by SPSS13.0 values than 0.05 were considered significant.
     Results:
     1.FAP showed negative expression in nomal skin. FAP showed positive expression in cytoplasm and cell membrane as yellow or brown granules in skin squamous cell carcinoma. Positive reaction product mainly localized in fibroblastic of tumor stroma's cytoplasm and cell membrane. Positive rate of FAP was 87%.There was significant difference in intensity of expression between well-differentiated and poorly differentiated, moderately differentiated and poorly differentiated(P< 0.05),but no difference between well-differentiated and moderately differentiated (P >0.05)
     2.Integrinβ1 showed positive expression in nomal skin. Positive expression mainly in cell membrane, and a small quantity in cytoplasm. In skin squamous cell carcinoma, positive expression mainly in tumour cell and tumour stroma cell membrane. Positive rate of Integrinβ1 was 52%.There was significant difference in intensity of expression between well-differentiated and moderately differentiated, well-differentiated differentiated and poorly differentiated(P<0.05),but no difference between moderately and poorly differentiated.
     3.The positive expression of FAP and the lower expression of Integrinβ1 are associated. The difference was significant(P<0.05).With the increasing expression of FAP,the expression of Integrinβ1 are lower.
     Conclusion
     1.FAP expressed in the skin squamous cell carcinoma, but did not express in normal skin. With the increased of the malignancy degree, the expression of FAP in skin squamous cell carcinoma is increased. It suggest that the expression of FAP is associated with tumor malignancy.
     2.The expression of Integrinβ1 was homogeneous in normal skin. The expression of positive rate in skin squamous cell carcinoma is lower than normal skin.With the increased of malignancy degree, the expression of Integrinβ1 with skin squamous cell carcinoma are decreased. It suggest that the expression of Integrinβ1 is associated with tumor malignancy.
     3.The expression of FAP and Integrin (31 are aberrant and play a negative correlation. It suggest that overexpression of FAP may be associated with decreased expression of Integrinβ1.Maybe they both have a common regulatory mechanism..
     4. To study the expression of FAP and Integrinβ1 in the skin squamous cell carcinoma, can become a new target for the therapy of.skin squamous cell carcinoma
引文
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