趋化因子CXCL5在前列腺癌中的表达和意义
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摘要
研究背景:前列腺癌(prostate cancer)是常见的男性泌尿系恶性肿瘤,近年来其发病率呈明显增长趋势,已成为威胁男性健康的常见疾病之一。目前,前列腺癌的发生机制尚不清楚,各种可能的影响因素仍在探索中。炎症与肿瘤的关系逐渐成为研究的热点,趋化因子作为炎症因子中的重要组成部分,其在各种肿瘤发生发展过程中的作用已被人们所关注。研究表明,趋化因子不仅仅参与了免疫反应,它也是肿瘤的发生、发展、侵袭及转移的重要调节因子之一。有些趋化因子能促进肿瘤的增殖,促进血管生成,诱导肿瘤细胞移动和粘附内皮细胞,加速肿瘤的扩散和转移;有些趋化因子能抑制肿瘤细胞生长,抑制血管生成,激发机体特异性和非特异性免疫应答,抑制肿瘤的生长和转移。CXCL5(CXC chemokine Ligand-5,CXC趋化因子配体-5)是促血管生成性CXC趋化因子家族中的一员,可由上皮细胞、内皮细胞、成纤维细胞、中性粒细胞、单核细胞和巨噬细胞产生,具有很强的粒细胞趋化作用。已有实验证实,CXCL5可促进非小细胞肺癌、胃癌及子宫内膜癌等肿瘤的发生、发展和转移。CXCL5在前列腺癌中的表达情况尚少有文献报道。本实验拟用免疫组化的方法检测CXCL5在前列腺癌的表达情况,以期探讨CXCL5在前列腺癌发生、发展及转移中的作用,为前列腺癌发生机制的研究提供实验依据。
     目的:观察CXCL5在前列腺癌中的表达,分析其与前列腺癌病理分级、临床分期及肿瘤转移的关系,探讨CXCL5在前列腺癌发生、发展、侵袭及转移中的作用。
     方法:收集中南大学湘雅医院病理科2003年10月-2008年10月间诊断为前列腺癌、PIN(prostate intraepithelial neoplasia,前列腺上皮内瘤)及前列腺增生的病例及其临床病理资料(前列腺癌41例,PIN 6例,前列腺增生14例),复阅HE染色病理组织切片。采用免疫组织化学SP法检测前列腺癌、PIN、及前列腺增生中CXCL5的表达,染色后阅片、评分,对比其在各组之间表达的差异,分析其表达水平与前列腺癌临床病理参数的关系。采用成组t检验和单因素方差分析进行统计学分析,P<0.05认为有统计学意义。
     结果:免疫组织化学结果显示CXCL5在41例前列腺癌组(染色评分10.02±2.055分)中表达,明显高于前列腺非癌组(染色评分4.45±1.317分)(P<0.05)。在不同病理分级前列腺癌组织中,从高分化组到低分化组CXCL5染色强度逐渐加深,染色评分逐渐升高,各组间比较有差异显著性意义(P<0.05)。CXCL5在Whitmore-Jewett分期系统C+D期组的表达明显高于A+B期组(P<0.05)。CXCL5在转移性前列腺癌组中的表达明显高于无转移组(P<0.05)。
     结论:CXCL5在前列腺癌组织中的表达高于前列腺增生和PIN。CXCL5的表达与前列腺癌病理分级恶性程度、临床分期、转移呈正相关。CXCL5可能参与了前列腺癌的发生、发展与转移过程。
Background: Prostate cancer is one of the most prevalent malignacies affecting men worldwide. And the number of afflicted men is increasing rapidly. Recent studies indicate that Chemokines, a family of inflammation factors, are important mediators in tumorogenesis, progression, invasion and metastasis of prostate cancer. CXCL5 is a proangiogenic CXC-type chemokine that is an inflammatory mediator and a powerful attractant for granulocytic immune cells. CXCL5 is secreted by several cell types, including epithelial cells, endothelial cells, fibroblasts, neutrophils, monocytes, and macrophages. It has been shown that CXCL5 could promote the growth and metastasis of non-small cell lung cancer, gastric cancer and endometrial cancer. The current study is intended to observe the expression of CXCL5 in prostate cancer, and explore the role CXCL5 plays in the progression and metastasis of prostate cancer.
     Objective: Investigate the expression of CXCL5 in human prostate cancer. Analysis the expression result with the pathologic grading of cancer, clinical stage and tumor metastasis. And explore the role CXCL5 plays in the progression and metastasis of prostate cancer.
     Methods: Collect the cases of prostate cancer, PIN and benign prostatic hyperplasia from Oct, 2003 to Oct, 2008 in pathological department of Xiangya Hospital of Central South University. The expression of CXCL5 in prostate cancer (n=41 tissues), benign prostatic hyperplasia (n=14 tissues) and PIN (n=6 tissues) were detected by immunohistochemistry SP method. The CXCL5 expression was compared among these different tissues. The relationship between CXCL5 expression and related clinicopathologic features was statistically analyzed.
     Results: The immunohistochemistry detection of CXCL5 in paraffin slides indicates that the staining scores of CXCL5 in prostate cancer(10.02±2.055) was significant higher than that in non-cancer tissue(4.45±1.317) (P<0.05). The cases were classified by the Whitmore-Jewett staging system and graded according to Gleason grading system. The expression of CXCL5 was associated with pathological grades and clinical stages. The staining scores of CXCL5 in C+D stages were significant higher than that in A+B stages(P<0.05). The expression of CXCL5 in metastatic prostate cancer was higher than that in prostate cancer without metastasis (P<0.05).
     Conclusion: The expression of CXCL5 in prostate cancer was significant higher than that in benign prostatic hyperplasia and prostate intraepithelial neoplasia. And it was associated with pathological grade , clinical stage and tumor metastasis. CXCL5 may play a role in the progression and metastasis of prostate cancer.
引文
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