摘要
目的:检测肝细胞癌中CXCR4的表达情况,结合临床病理资料分析CXCR4对肝癌患者临床预后的影响,为临床预测肝癌的预后提供理论依据;检测肝癌中肿瘤微血管密度,结合CXCR4的表达情况初步探讨CXCR4与肝癌中肿瘤血管生成之间的关系。
方法:收集2000年1月至2001年12月于我院手术切除的符合试验条件的117例肝细胞癌患者的临床病理资料,采用免疫组织化学方法检测标本中CXCR4的表达状况,分析CXCR4的表达情况与临床病理因素之间的关系,进一步进行生存分析和Logistic回归研究,分析各因素对肝癌预后的预测价值;免疫组织化学方法染色标本中的CD34,检测肿瘤微血管密度,结合CXCR4的表达情况初步分析CXCR4在肿瘤微血管形成过程中的作用。
结果:CXCR4在全部117例肝癌组织中呈不同程度表达,其中CXCR4(+)组32例,CXCR4(++)组45例,CXCR4(+++)组40例,其表达情况在患者性别、年龄、HBsAg、AFP、肝硬化程度、肿瘤Edmonson分级、肿瘤直径和术前Child-Pugh分级之间的差异无统计学意义(p＞0.05),在肿瘤是否有血管侵犯之间的差异存在统计学意义(p＜0.05)。单因素分析显示:患者肝硬化程度、肿瘤直径、肿瘤Edmonson分级、肿瘤侵犯血管及CXCR4表达情况是影响患者无瘤生存时间的危险因素(p＜0.05)。COX回归显示患者肝硬化程度、肿瘤直径、肿瘤侵犯血管及CXCR4表达情况是影响患者无瘤生存时间的独立危险因素(p＜0.05)。Logistic回归显示CXCR4表达情况、肿瘤直径、患者肝硬化程度和肿瘤侵犯血管是影响患者复发/转移的独立危险因素。CD34在全部117例标本中存在不同程度表达,应用肿瘤微血管密度计数方法计算显示:CXCR4(+)、CXCR4(++)和CXCR4(+++)组中MVD分别为15.25±5.61个、22.82±6.49个和28.88±8.65个,方差分析显示三组之间的差异存在统计学意义(p＜0.05)。
结论:肝细胞癌中存在不同程度的CXCR4的表达,其表达强度与肿瘤血管侵犯明显相关,是预测肝癌术后转移复发的独立危险因素。
Objective:To evaluate the expression of CXCR4 in hepatocellular carcinoma(HCC) and investigate its possible prognostic value.To detect the microvessel density(MVD) of HCC and investigate the role of CXCR4 in the angiogenesis of HCC.
Methods:clinical and pathological data of 117 qualified HCC patients in Cancer Hospital of Tianjin Medical University,from Jan 2000 to Dec 2001 were collected. Immunohistochemistry method was applied to detect the expression of CXCR4 and CD34 in HCC.The value of CXCR4 in predicting the prognosis of HCC was evaluated by survival analysis.The relationship between the expression of CXCR4 and MVD was also analyzed.
Results:CXCR4 was positive in all of 117 specimens with different intensity of staining.There were 32 patients in CXCR4(+)group,45 in CXCR4(++)group,and 40 in CXCR4(+++)group.No significant difference was found in each group when compared by sex,age,HBsAg,AFP,liver cirrhosis,Edmonson stage,tumor diameter, preoperative Child-Pugh classification(p＞0.05).However,significant difference was found in tumor vascular invasion among the three groups(p＜0.05).Kaplan-Meier analysis demonstrated liver cirrhosis,tumor diameter,tumor Edmonson classification, tumor vascular invasion and CXCR4 expression were significant factors influencing the disease-free survival of HCC patients(p＜0.05).COX regression showed liver cirrhosis,tumor diameter,tumor vascular invasion and CXCR4 expression were significant risk factors influencing the disease-free survival of HCC patients(p＜0.05). Logistic.regression indicated that liver cirrhosis,tumor diameter,tumor vascular invasion and CXCR4 experssion were risk factors of tumor metastasis and recurrence (p＜0.05).CD34 was detected in all specimens.MVD was 15.25±5.61,22.82±6.49 and 28.88±8.65 in CXCR4(+),CXCR4(++)and CXCR4(+++)group,respectively. ANOVA analysis showed significant difference among the three groups(p＜0.05). Conclusions:CXCR4 is expressed in HCC at different levels.The expression of CXCR4 is closely associated with tumor vascular invasion.Over-expression of CXCR4 is an independent risk factor in predicting the metastasis and recurrence of HCC.
引文
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