Midkine expression in colorectal tumors: Correlation with Ki-67 labeling in sporadic, but not ulcerative colitis-associated ones

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.