Fascin及VEGF在膀胱移行细胞癌中的表达及意义
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摘要
研究背景与目的：膀胱癌是泌尿系统中最常见的恶性肿瘤,其生物学行为有多中心、易复发、及浸润性生长的特点。肿瘤的侵袭、转移是造成患者死亡的主要原因。目前膀胱癌发生、发展机制尚不清楚,且尚缺乏特异的诊断及判断预后的标记物。Fascin蛋白是一种结构独特,进化保守的肌动蛋白结合蛋白,定位于细胞膜皱褶、微棘和应力纤维,可促使活性细胞细胞膜突起并增加细胞运动性。近年来Fascin蛋白在其他肿瘤例如食管鳞状细胞癌、胃癌、结肠癌、卵巢癌等方面国内外常有报道。而国外针对Fascin蛋白在膀胱癌方面的研究目前尚少,国内未见报道。本实验通过对Fascin与血管内皮细胞生长因子在人膀胱移行癌中的表达进行检测并联系临床病理指标进行分析,以初步探讨Fascin的表达对肿瘤生物学行为的影响及其与血管内皮生长因子的相关性,并判断其是否可作为一个有用的肿瘤恶性程度评价指标。
研究资料与方法：采用免疫组织化学SABC (StrePtAvidin-Biotin ComPlex)法对天津医科大学第二附属医院2004年2月至2008年7月间手术切除并经病理证实、资料完整的56例膀胱移行细胞癌组织及10例正常膀胱粘膜组织进行Fascin、VEGF的检测,并对两者表达情况与BTCC临床病理特征的关系,两者在BTCC中表达的相关性进行了统计分析。采用SPSS13.0统计软件包进行统计学处理,以a=0.05作为统计学检验的显著性水准。
实验结果：1. Fascin蛋白在10例正常膀胱组织中不表达,而56例BTCC组织中有41例表达阳性,占73.21%,差异有显著意义(P<0.01);VEGF蛋白在10例正常膀胱组织中不表达,而在56例BTCC组织中有34例表达阳性,占60.71%,差异有显著意义(P<0.01)。
2. Fascin阳性表达率在不同年龄、性别、肿瘤大小及数目的患者之间,无显著性差异(P>0.05)；但随着病理分级增加,Fascin蛋白表达率及表达强度均增加,在Ⅰ、Ⅱ、Ⅲ级BTCC中,阳性表达率分别为36.36%、76.00%、90.00%(18/20),差别具有显著性意义(P<0.01)。随着BTCC临床分期的增高,Fascin蛋白的阳性表达呈上升趋势,在Ta-TI(浅表型)和T2-T4(浸润型)阳性表达率分别为50.00%、88.24%,差别具有显著性意义(P<0.01)。Fascin蛋白在初发组中的阳性表达率为41.18%,而复发组的异常表达率为87.18%,两组间比较差异显著(P<0.01)。
3. VEGF阳性表达率在不同年龄、性别、肿瘤大小及数目的患者之间,无显著性差异(P>0.05)；随着病理分级增加,VEGF蛋白表达率及表达强度均增加,在Ⅰ、Ⅱ、Ⅲ级BTCC中,阳性表达率分别为27.27%、56.00%、85.00%,差别具有显著性意义(P<0.01)。随着BTCC临床分期的增高,VEGF蛋白的阳性表达呈上升趋势,在Ta-T1(浅表型)和T2-T4(浸润型)阳性表达率分别为40.91%、73.53%,差别具有显著性意义(P<0.05)。VEGF蛋白在初发组中的阳性表达率为29.41%,而复发组的异常表达率为74.36%,两组间比较差异有显著意义(P<0.01)。4.在56例BTCC组织中,Fascin和VEGF蛋白二者共同表达阳性31例,共同表达阴性12例,两者在膀胱移行细胞癌中的表达具有相关性(Pearson列联系数=0.4769,P<0.011。
结论：1. Fascin在膀胱移行细胞癌组织中随病理分级的增高而表达增强,在临床分期中随肿瘤的浸润及发展表达增强。可为膀胱癌的早期发生及生长发展、浸润提供参考指标。2. VEGF在膀胱移形细胞癌中随着病理分级的增高而表达增强,在临床分期中随肿瘤的浸润及发展表达增强。3. Fascin的阳性表达与VEGF在膀胱移行细胞癌中的阳性表达密切相关,证实Fascin和VEGF在肿瘤的发生发展及浸润中存在协同作用,两者协调参与了膀胱癌的发展浸润过程。4. Fascin和VEGF可作为膀胱癌发生发展、浸润的参考指标,对临床开展肿瘤防治新途径提供理论依据。
Background and Objects:The bladder tumor is the one of most common malignant tumor.the biological feature is multicentre, easy relaPse, and infiltrative growth.the invasion and metastasis of tumor is the leading cause of death in Patient. Now,the mechanism of the growth and Progression of BTCC is still ambiguity and there is no sPecific marker that is used to diagnose BTCC and judge the Prognosis of BTCC.Fascin, a structuarlly unique and evolutionarily conserved actin-bunding Protein that is found in membrane ruffles, microsPikes, and stress fiber, induces membrane Protrusions and increases cell motility in various transformed cells.We found Fascin usually had uP-regulation in tumors from epithelial tissue. Fascin protein, recently, is often reported to be found in tumors,such as esophageal squamous cell carcinoma, gastric carcinoma, colon carcinoma, ovarian cancer and so on.However,there is no report over Fascin Protein in bladder cancer in china,little in foreign country. By studying the immunoreactivity of Fascin and VEGF and analysising clinicopathlogical index in BTCC, my experiment investigate the effect of Fascin protein on biological behaviour and correlation with VEGF in order to judge the possibility Fascin being a useful marker for the malignant BTCC.
Materials and Method:Ten samples from normal bladder tissue and 56 samples from transitional cell carcinoma of bladder were collected. Bladder cancer sampleswere obtained from surgically-resected sPecimens from the Second Affiliated HosPital of Tianjin University between 2004 and 2008.The Patients had no Prior chemotheraPy or radiotheraPy.All these cancers were diagnosed pathologically. The expression of Fascin and VEGF was examined by SABC (StrePtAvidin-Biotin Complex) immunohistochemistry in 56 Paraffin-embedded tissue specimens and 10 control groups of normal bladder tissues with analysis by SPSS 13.0
Results:l.In cancer cells, Fascin and VEGF expression were found mainly in the cytoplasm.The positive expression rate of Fascin and VEGF in normal bladder tissue was 0%, while the positive expression rate of Fascin and VEGF was statistically significant(P<0.01).2. The Positive expression of Fascin in transitional cell carcinoma of bladder had no distinct difference in age, sex, tumorsize and tumor quantity(P>0.05), but it had a close correlation with the degrees of histological grades(P<0.01), clinical stages (P<0.01), and Primary or recurrent carcinoma(P<0.01).3.The Positive expression of VEGF in transitional cell carcinoma of bladder had no distinct difference in age, sex, tumorsize and tumor quantity(P>0.05), but it had a close correlation with the degrees of histological grades (P<0.01), clinical stages (P<0.05), and Primary or recurrent carcinoma (P<0.01). 4. The Positive expression of Fascin and VEGF in 56 cases of transitional cell carcinoma of bladder was closely associated with each other. The expression of Fascin was closely correlated with that of VEGF (liner index of Pearson=0.4769, P<0.01)
Conclusion:1.The expression of Fascin increases in high-grade bladder transitional cell carcinoma and the over-expression of Fascin is correlated with the stage of invasive tumor.It Provides referencing index and the development and invasion of bladder carcinoma.2.The expression of VEGF increases in high-grade bladder transitional cell carcinoma and the over-expression of VEGF is correlated with the stage of invasive tumor.3.A close correlation between expression of VEGF and Fascinin transitional cell carcinoma of bladder was observed. It is indicated that there is certain regulation bewteen Fascin and VEGF. They contribute to the angiogenesis and metastasis of bladder carcinoma in coordination.4.It is suggested that the Positive experssion of Fascin and VEGF might be the referencing indxe of the development and invasion of bladder carcinoma. It is shown thatFascin and VEGF may provide theoretical fundation of chemoPreventive stategy for bladder cancer in the future.
研究资料与方法：采用免疫组织化学SABC (StrePtAvidin-Biotin ComPlex)法对天津医科大学第二附属医院2004年2月至2008年7月间手术切除并经病理证实、资料完整的56例膀胱移行细胞癌组织及10例正常膀胱粘膜组织进行Fascin、VEGF的检测,并对两者表达情况与BTCC临床病理特征的关系,两者在BTCC中表达的相关性进行了统计分析。采用SPSS13.0统计软件包进行统计学处理,以a=0.05作为统计学检验的显著性水准。
实验结果：1. Fascin蛋白在10例正常膀胱组织中不表达,而56例BTCC组织中有41例表达阳性,占73.21%,差异有显著意义(P<0.01);VEGF蛋白在10例正常膀胱组织中不表达,而在56例BTCC组织中有34例表达阳性,占60.71%,差异有显著意义(P<0.01)。
2. Fascin阳性表达率在不同年龄、性别、肿瘤大小及数目的患者之间,无显著性差异(P>0.05)；但随着病理分级增加,Fascin蛋白表达率及表达强度均增加,在Ⅰ、Ⅱ、Ⅲ级BTCC中,阳性表达率分别为36.36%、76.00%、90.00%(18/20),差别具有显著性意义(P<0.01)。随着BTCC临床分期的增高,Fascin蛋白的阳性表达呈上升趋势,在Ta-TI(浅表型)和T2-T4(浸润型)阳性表达率分别为50.00%、88.24%,差别具有显著性意义(P<0.01)。Fascin蛋白在初发组中的阳性表达率为41.18%,而复发组的异常表达率为87.18%,两组间比较差异显著(P<0.01)。
3. VEGF阳性表达率在不同年龄、性别、肿瘤大小及数目的患者之间,无显著性差异(P>0.05)；随着病理分级增加,VEGF蛋白表达率及表达强度均增加,在Ⅰ、Ⅱ、Ⅲ级BTCC中,阳性表达率分别为27.27%、56.00%、85.00%,差别具有显著性意义(P<0.01)。随着BTCC临床分期的增高,VEGF蛋白的阳性表达呈上升趋势,在Ta-T1(浅表型)和T2-T4(浸润型)阳性表达率分别为40.91%、73.53%,差别具有显著性意义(P<0.05)。VEGF蛋白在初发组中的阳性表达率为29.41%,而复发组的异常表达率为74.36%,两组间比较差异有显著意义(P<0.01)。4.在56例BTCC组织中,Fascin和VEGF蛋白二者共同表达阳性31例,共同表达阴性12例,两者在膀胱移行细胞癌中的表达具有相关性(Pearson列联系数=0.4769,P<0.011。
结论：1. Fascin在膀胱移行细胞癌组织中随病理分级的增高而表达增强,在临床分期中随肿瘤的浸润及发展表达增强。可为膀胱癌的早期发生及生长发展、浸润提供参考指标。2. VEGF在膀胱移形细胞癌中随着病理分级的增高而表达增强,在临床分期中随肿瘤的浸润及发展表达增强。3. Fascin的阳性表达与VEGF在膀胱移行细胞癌中的阳性表达密切相关,证实Fascin和VEGF在肿瘤的发生发展及浸润中存在协同作用,两者协调参与了膀胱癌的发展浸润过程。4. Fascin和VEGF可作为膀胱癌发生发展、浸润的参考指标,对临床开展肿瘤防治新途径提供理论依据。
Background and Objects:The bladder tumor is the one of most common malignant tumor.the biological feature is multicentre, easy relaPse, and infiltrative growth.the invasion and metastasis of tumor is the leading cause of death in Patient. Now,the mechanism of the growth and Progression of BTCC is still ambiguity and there is no sPecific marker that is used to diagnose BTCC and judge the Prognosis of BTCC.Fascin, a structuarlly unique and evolutionarily conserved actin-bunding Protein that is found in membrane ruffles, microsPikes, and stress fiber, induces membrane Protrusions and increases cell motility in various transformed cells.We found Fascin usually had uP-regulation in tumors from epithelial tissue. Fascin protein, recently, is often reported to be found in tumors,such as esophageal squamous cell carcinoma, gastric carcinoma, colon carcinoma, ovarian cancer and so on.However,there is no report over Fascin Protein in bladder cancer in china,little in foreign country. By studying the immunoreactivity of Fascin and VEGF and analysising clinicopathlogical index in BTCC, my experiment investigate the effect of Fascin protein on biological behaviour and correlation with VEGF in order to judge the possibility Fascin being a useful marker for the malignant BTCC.
Materials and Method:Ten samples from normal bladder tissue and 56 samples from transitional cell carcinoma of bladder were collected. Bladder cancer sampleswere obtained from surgically-resected sPecimens from the Second Affiliated HosPital of Tianjin University between 2004 and 2008.The Patients had no Prior chemotheraPy or radiotheraPy.All these cancers were diagnosed pathologically. The expression of Fascin and VEGF was examined by SABC (StrePtAvidin-Biotin Complex) immunohistochemistry in 56 Paraffin-embedded tissue specimens and 10 control groups of normal bladder tissues with analysis by SPSS 13.0
Results:l.In cancer cells, Fascin and VEGF expression were found mainly in the cytoplasm.The positive expression rate of Fascin and VEGF in normal bladder tissue was 0%, while the positive expression rate of Fascin and VEGF was statistically significant(P<0.01).2. The Positive expression of Fascin in transitional cell carcinoma of bladder had no distinct difference in age, sex, tumorsize and tumor quantity(P>0.05), but it had a close correlation with the degrees of histological grades(P<0.01), clinical stages (P<0.01), and Primary or recurrent carcinoma(P<0.01).3.The Positive expression of VEGF in transitional cell carcinoma of bladder had no distinct difference in age, sex, tumorsize and tumor quantity(P>0.05), but it had a close correlation with the degrees of histological grades (P<0.01), clinical stages (P<0.05), and Primary or recurrent carcinoma (P<0.01). 4. The Positive expression of Fascin and VEGF in 56 cases of transitional cell carcinoma of bladder was closely associated with each other. The expression of Fascin was closely correlated with that of VEGF (liner index of Pearson=0.4769, P<0.01)
Conclusion:1.The expression of Fascin increases in high-grade bladder transitional cell carcinoma and the over-expression of Fascin is correlated with the stage of invasive tumor.It Provides referencing index and the development and invasion of bladder carcinoma.2.The expression of VEGF increases in high-grade bladder transitional cell carcinoma and the over-expression of VEGF is correlated with the stage of invasive tumor.3.A close correlation between expression of VEGF and Fascinin transitional cell carcinoma of bladder was observed. It is indicated that there is certain regulation bewteen Fascin and VEGF. They contribute to the angiogenesis and metastasis of bladder carcinoma in coordination.4.It is suggested that the Positive experssion of Fascin and VEGF might be the referencing indxe of the development and invasion of bladder carcinoma. It is shown thatFascin and VEGF may provide theoretical fundation of chemoPreventive stategy for bladder cancer in the future.
引文
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