肾癌原发灶与骨转移灶配对组织的免疫组化分析

Immunohistochemical analysis of primary renal cell carcinomas and paired bone metastases

目的 比较肾癌骨转移灶与原发灶的组织病理学及免疫组化的差异.方法 回顾性分析2003年1-9月收治的19例肾癌合并骨转移且先后切除原发灶和骨转移灶患者的临床资料,收集患者术后石蜡标本,进行组织病理学及免疫组化分析,比较肾癌骨转移灶与原发灶的Fuhrman分级差异和Ki-67、CD34、血管内皮生长因子受体2（VEGFR2）、表皮生长因子受体（EGFR）以及趋化因子CXC亚家族受体4（CXCR4）的表达差异,通过血管内皮特异的CD34染色计数微血管密度（MVD）值.结果 7例患者骨转移灶Fuhrman分级高于原发灶;19例骨转移灶与原发灶Fuhrman分级比较差异有统计学意义（P=0.008）.原发灶Ki-67标记指数为（4.00±3.96）％,转移灶为（7.90±7.38）％（P=0.033）;原发灶MVD为58.13±22.90,转移灶为46.71 ±25.40（P=0.026）;原发灶VEGFR2表达评分为4.68± 1.20,转移灶为4.05±1.58（P=0.014）;组间比较差异均有统计学意义.原发灶EGFR表达评分为5.89± 1.05,转移灶为5.47±1.12,差异无统计学意义（P=0.134）.细胞膜和细胞质CXCR4表达评分原发灶为1.74± 1.97,转移灶为2.16±1.64,差异无统计学意义（P=0.414）.细胞核CXCR4表达评分原发灶为2.52±2.09,转移灶为3.42± 1.95,差异有统计学意义（P=0.009）.结论 肾癌骨转移灶的Fuhrman分级、Ki-67标记指数以及细胞核CXCR4表达高于原发灶,MVD和VEGFR2表达低于原发灶,这些可能是肾癌骨转移预后不良、抗血管生成靶向治疗效果不佳的原因.

Objective To compare the histopathologic and immunohistochemical differences between primary renal cell carcinomas and paired bone metastases in order to discuss the significance in the selection of standard targeted therapies.Methods The clinical data of 19 patients who underwent nephrectomy and resection of bone metastases successively from January 2003 to September 2013 were analysed retrospectively.The paraffin-embedded surgical samples of all the patients were obtained for histopathologic and immunohistochemical analysis.The differences of Fuhrman grades,expression of Ki-67,CD34,vascular endothelial growth factor receptor 2 （VEGFR2）,epidermal growth factor receptor （EGFR） and CXC subfamily receptor 4 （CXCR4） were compared between primary renal cell carcinomas and their paired bone metastases.Microvessel density （MVD） was evaluated by the CD34 immunostaining.Results The Fuhrman grades of samples from bone metastases were higher than that of primary tumors （36.8％,7/19） （P=0.008）.The Ki-67 label index was （4.00±3.96）％ in primary tumors and （7.90±7.38）％ in bone metastases （P=0.033）.The microvessel density （MVD） was 58.13±22.90 in primary tumors and 46.71±25.40 in the bone metastases （P=0.026）.The immunohistochemistry scores of VEGFR2 were 4.68±1.20 in primary tumors and 4.05±1.58 in bone metastases （P=0.014）.The immunohistochemistry scores of EGFR were 5.89±1.05 in primary tumors and 5.47± 1.12 in bone metastases （P=0.134）.The immunohistochemistryscores of CXCR4 in cytomembrane and cytoplasm were 1.74±1.97 in primary tumors and 2.16± 1.64 in bone metastases （P=0.414）.The inununohistochemistry scores of CXCR4 in cell nucleus were 2.52±2.09 in primary tumors and 3.42±1.95 in bone metastases （P=0.009）.Conclusions The Fuhrman grades and the expression of Ki-67 and CXCR4 in cell nucleus were higher in bone metastases than that in the primary renal cell carcinomas.The MVD and the expression of VEGFR2 were lower in bone metastases than that in the primary tumors.The above alternations may contribute to the poor prognosis of bone metastasis and the poor result of angiosuppressive therapy.