Midkine expression in colorectal tumors: Correlation with Ki-67 labeling in sporadic, but not ulcerative colitis-associated ones
Midkine expression in colorectal tumors: Correlation with Ki-67 labeling in sporadic, but not ulcerative colitis-associated ones
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DOI：
10.1111/j.1440-1827.2007.02095.x
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发表时间：
2007-05-01
影响因子：
2.2
通讯作者：
Okayasu, Isao
中科院分区：
文献类型：
--
作者：
Tokuyama, Wataru;Mikami, Tetuo;Okayasu, Isao
中期因子(Midkine，MK)是一种由维甲酸反应基因编码的肝素结合生长因子。为探讨MK在结直肠癌发生中的可能作用，对散发性和溃疡性结肠炎(UC)相关肿瘤进行了蛋白表达的免疫组织化学检测。MK在正常粘膜、腺瘤伴低级别不典型增生(LGD)、腺瘤伴高级别不典型增生(HGD)和浸润性腺癌中的表达差异有统计学意义：随着肿瘤的进展，MK的表达增加。UC相关病变(UC再生黏膜、UC相关异型增生和UC相关腺癌)也有相似的变化。MK在UC相关皮损中的表达显著高于正常粘膜，但在UC相关皮损之间无显著差异。但在UC相关的异型增生中，MK的表达在上、下半部之间无明显差异，而在LGD和HGD的腺瘤中，MK的表达在上半部分明显高于下半部分，与细胞增殖区相对应。此外，在散发性但不与UC相关的病变中，分别与Ki-67和单链DNA标记相关联，反映了细胞的增殖活性和细胞凋亡。这些结果表明，MK参与了散发性结直肠癌和UC相关肿瘤的发生发展，但在这两种肿瘤的发生发展中可能起着不同的作用。
Midkine (MK) is a heparin-binding growth factor encoded by a retinoic acid responsive gene. To investigate the possible contribution of MK to genesis of colorectal carcinomas, an immunohistochemical examination of protein expression was conducted in sporadic and ulcerative colitis (UC)-associated tumors. MK expression significantly differed among normal mucosa, adenomas with low-grade dysplasia (LGD), adenomas with high-grade dysplasia (HGD) and invasive adenocarcinomas: MK expression was increased along with tumor progression. UC-associated lesions (regenerative mucosa of UC, UC-associated dysplasia and UC-associated adenocarcinoma) had similar variations. MK expression in UC-associated lesions was significantly higher than in normal mucosa, although there was no significant difference among UC-associated lesions. However, in UC-associated dysplasia, MK expression did not differ between the upper and lower halves, in contrast to adenoma with LGD and HGD, in which MK expression was significantly higher in the upper than lower halves, corresponding to cell proliferative zone. Furthermore, correlations with Ki-67 and single-strand DNA labeling, respectively, reflecting cellular proliferative activity and apoptosis, were noted in sporadic but not UC-associated lesions. These results suggest that MK is involved in genesis/development of sporadic colorectal tumors as well as of UC-associated tumors, but might contribute differently to genesis/development in these two types of tumors.