CXCL12及其受体CXCR4在胰腺癌中的表达及其与淋巴管生成的相关性

目的 研究胰腺癌中CXCL12及其受体CXCR4 的表达和其在胰腺癌淋巴管生成中的作用. 方法选取2005年1月至2007年12月间经外科手术治疗且临床资料完整的胰腺癌病例30例,其中男性17例,女性13例,年龄35～78岁,中位年龄57.2岁.采用免疫组织化学、RT-PCR和实时荧光定量PCR检测30例胰腺癌、癌旁组织、正常胰腺和胰周淋巴结标本中CXCL12、CXCR4的表达情况.形态计量学图像分析法测定并分析胰腺癌微血管密度(MLVD)与CXCL12、CXCR4表达的关系.结果 CXCL12在胰腺癌组织中呈低表达,正常胰腺、癌旁组织和胰周淋巴结中呈中等表达(P<0.01).CXCR4在胰腺癌、癌旁组织和胰周淋巴结呈高表达,在正常胰腺组织呈低表达;RT-PCR和实时荧光定量PCR均证实上述结果.MLVD在胰腺癌TNM分期Ⅲ～Ⅳ期组显著高于Ⅰ～Ⅱ期组(P<0.05),淋巴结转移阳性组显著高于阴性组(P<0.01),CXCR4阳性者MLVD明显高于阴性者(P=0.003). 结论 CXCR4的表达与胰腺癌淋巴结转移密切相关,其高表达对胰腺癌微淋巴管的生成可能起促进作用.

Quantitative analysis and significance of CXCL12 and CXCR4 expression with lymphangiogenesis of pancreatic adenocarcinoma

Objective To investigate the expression of CXCL12,its receptor CXCR4 and its correlations with clinical pathology and lymphangiogenesis in pancreatic adenocarcinoma (PAC). MethodsThe tissue samples were obtained from 30 patients with PAC by surgery between January 2005 and December 2007,which including PAC,the cancerous peripheral tissues,the normal pancreatic tissues and peripheral lymphonodes. The patients age ranged from 35 to 78 years old (median 57.2 years old). The expressions of CXCL12 and CXCR4 in these tissues were assayed by immunohistochemical staining,RT-PCR and fluorescence quantitative real-time PCR. Results In the immunohistochemical staining, the CXCL12 protein mainly located in the normal pancreatic cell envelopes and/or cytolymphs. In the immunohistochemical staining, the CXCR4 protein mainly located in the cell envelopes and/or cytolymphs of PAC. The results of RT-PCR and fluorescence quantitative real-time PCR indicated that the expression levels of CXCR4 mRNA in PAC tissues,the cancerous peripheral tissues and peripheral lympho nodes were higher than that in the normal pancreatic tissues(P<0.01). The MLVD in PAC were detected by morphometric analysis respectively. The level of MLVD in Ⅲ-Ⅳ stages was higher than Ⅰ-Ⅱ stages of PAC (P<0.01),and in these cases which had lymphatic metastasis,the level of MLVD significantly increased (P<0.01). And there was no correlation between the differentiation and histology types of PAC(P>0.05). There was 22 samples that the CXCR4 protein was positive,and among these samples the MLVD was higher than that in negative group of CXCR4 protein(P=0.003). Conclusions The expression of CXCR4 was significantly associated with lymphatic metastasis of PAC,and the higher expression of CXCR4 in PAC tissues was significantly associated with lymphangiogenesis of PAC.