BRAF和EphB2在人结直肠锯齿状腺瘤中的表达及意义

Expression and significance of BRAF and EphB2 in human colorectal serrated adenomas

目的:探讨鼠类肉瘤滤过性病毒致癌基因同源体B1(v-raf murine sarcoma viral oncogene homolog B1,BRAF)和生促红素人肝细胞蛋白(erythropoietin-producing hepatoma cell line B2,EphB2)在人结直肠锯齿状腺瘤中的表达及其意义。方法:收集滨州医学院附属医院1996年1月至2008年5月10例正常结直肠肠黏膜、21例增生性息肉、22例锯齿状腺瘤、55例腺瘤性息肉(18例管状腺瘤、16例管状绒毛状腺瘤、21例绒毛状腺瘤)石蜡标本。免疫组织化学法检测BRAF和EphB2蛋白的表达量,同时观察蛋白的表达部位。结果:增生性息肉中BRAF蛋白阳性细胞多位于隐窝中下区域,腺瘤性息肉的阳性细胞多表达位于隐窝上部区域,而锯齿状腺瘤阳性细胞多表达于隐窝全层。锯齿状腺瘤与腺瘤性息肉的BRAF蛋白表达量相近[(0.129±0.030)vs(0.130±0.026),P>0.05],但远高于增生性息肉[(0.129±0.030)vs(0.102±0.014),P<0.01];锯齿状腺瘤、管状腺瘤、管状绒毛状腺瘤、绒毛状腺瘤之间BRAF蛋白表达量差异无统计学意义[(0.129±0.030)vs(0.116±0.019),(0.119±0.037),(0.122±0.008),P>0.05]。增生性息肉中EphB2蛋白阳性细胞多位于隐窝中下区域细胞膜上,腺瘤性息肉EphB2蛋白阳性细胞位于隐窝上部,而锯齿状腺瘤EphB2蛋白阳性细胞表达于隐窝全层。锯齿状腺瘤与腺瘤性息肉的EphB2蛋白表达量相近[(0.138±0.024)vs(0.139±0.025),P>0.05],而远高于增生性息肉[(0.138±0.024)vs(0.169±0.018),P<0.01];锯齿状腺瘤与管状腺瘤、管状绒毛状腺瘤、绒毛状腺瘤间EphB2蛋白表达量无区别[(0.138±0.024)vs(0.143±0.027),(0.139±0.028),(0.133±0.021),P>0.05]。结论:BRAF和EphB2蛋白在增生性息肉、腺瘤性息肉中隐窝部分区域表达,而在锯齿状腺瘤中隐窝全层表达,提示锯齿状腺瘤是一类独立的不同于腺瘤性息肉的结直肠肿瘤。

Objective：To discuss the expression and significance of v-raf murine sarcoma viral oncogene homolog B1（BRAF） and erythropoietin-producing hepatoma cell line B2（EphB2） in human colorectal serrated adenomas.Methods： Collect 10 paraffin specimens of normal mucosa,21 cases of hyperplastic polyp,22 cases of serrated adenomas and 55 cases of traditional colorectal adenomas（18 tubular adenomas,16 tubulovillous adenomas,21 villous adenomas） in the Affiliated Hospital of Binzhou Medical College between Jan.1996 to May.2008.The expression levels and sites of BRAF and EphB2 protein were examined by immunohistochemical method.Results： Most BRAF protein positive cells in hyperplastic polyp were located in the lower crypt,those in adenomatous polyp located in upper crypt,and those in serrated adenomas almost expressed in the whole crypt.The expression of BRAF protein was similar in serrated adenomas and adenomatous polyp（0.129±0.030 vs 0.130±0.026,P0.05）,while more higher than that in hyperplastic polyp（0.129±0.030 vs 0.102±0.014,P0.01）.There was no significant difference in BRAF protein expression among the serrated adenomas,tubular adenomas,tubulovillous adenomas and villous adenomas（0.129±0.030 vs 0.116±0.019,0.119±0.037,0.122±0.008,P0.05）.The EphB2 protein positive cells in hyperplastic polyp was almost located in the membrane of the middle and lower region of crypt,those in adenomatous polyp located in the upper crypt,and those in serrated adenomas expressed in the whole crypt.The EphB2 protein expression in serrated adenomas and adenomatous polyp was similar（0.138±0.024 vs 0.139±0.025,P0.05）,but much higher than that in hyperplastic polyp（0.138±0.024 vs 0.169±0.018,P0.01）.No significant difference was found in EphB2 among serrated adenomas,tubular adenomas,tubulovillous adenomas and villous adenomas（0.138±0.024 vs 0.143±0.027,0.139±0.028,0.133±0.021,P0.05）.Conclusion： BRAF and EphB2 proteins both in hyperplastic polyp and adenomatous polyp are expressed partly in crypt,while those in colorectal serrated adenomas are expressed in the whole crypt,indicating that serrated adenomas may be an independent tumor difference from adenomatous polyp.