大肠癌Ref-1/APE的表达特点及其意义

Feature of Ref-1/APE expression and its correlation with vascular endothelial growth factor expression and microvessel density in colorectal cancer

目的探讨大肠癌氧化还原因子-1(redoxfactor-1,Ref-1),又称脱嘌呤/脱嘧啶核酸内切酶(apurinic/apyri-midinicendonuclease,APE),在大肠癌的表达特点及其与血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)和血管密度的关系。方法应用免疫组化S-P法检测110例大肠癌和40例非癌区大肠组织中Ref-1/APE和VEGF的表达,采用血管内皮特异标记物CD31标记并计数肿瘤微血管密度(microvesseldensity,MVD),最后分析Ref-1/APE与VEGF和MVD的关系。结果所有大肠癌和非癌区大肠组织都有Ref-1/APE表达,但是其在细胞内的定位有所不同。40例非癌区大肠组织细胞核都有Ref-1/APE表达,仅5例有胞质表达(5/40,12·5%);而110例大肠癌中有79例(79/110,71·81%)细胞质有Ref-1/APE表达,比例显著高于非癌区大肠组织(P<0·01)。而且细胞质Ref-1/APE阳性表达的大肠癌较无细胞质表达者VEGF阳性率显著增加(P<0·05),MVD也显著增高(P<0·05)。结论大肠癌Ref-1/APE移位于细胞质的异常表达可能涉及大肠癌的发生,并且可能与VEGF表达和肿瘤血管生成有关。

Objective To study the features of redox faetor-1/apurinie endonuelease （Ref-1/APE） expression and its correlation with vascular endothelial growth factor （VEGF） expression and microvessel density （MVD） in colorectal cancer （CRC）. Methods The expression of Ref-1/APE and VEGF was detected by SP immunohistochemical technique in 110 cases of CRC and 40 cases of non-cancerous large intestine. MVD were evaluated by immunohistochemistry with anti-human CD31 antibody. Then, the relationship between the expression of Ref-1/APE or VEGF and MVD was analyzed. Results Protein expression of Ref-1/APE was noted in all colorectal cancer and non-cancerous large intestine tissues, but the cellular location of Ref-1/APE was different. The Ref-1/APE expression of non-cancerous large intestine tissues mainly located in the nucleus, while the shifts of Ref-1/APE from nucleus to cytoplasm was observed in 79 of 110 （71.81% ） colorectal cancer tissues. Their difference was highly significant（P 〈0. 01 ）. Furthermore, the cytoplasmic location of Ref-1/ APE was significantly correlated with the overexpression of VEGF and higher MVD in CRC （ P 〈 0. 05 ）. Conclusion Shift of Ref-1/APE from nucleus to cytoplasm could play role in carcinogenesis, especially in VEGF overexpression and angiogenesis of CRC.