Mulder J W, Wielenga V J, Polak M M, van den Berg F M, Adolf G R, Herrlich P, Pals S T, Offerhaus G J
Department of Pathology, University of Amsterdam, The Netherlands.
Gut. 1995 Jan;36(1):76-80. doi: 10.1136/gut.36.1.76.
Colorectal tumorigenesis evolves through a series of molecular genetic changes, providing putative markers for tumour progression. This study investigated the relation between expression of the tumour suppressor gene p53 and splice variants v5 and v6 of the cell adhesion molecule CD44 by immunohistochemistry on tissue samples of early adenomas (n = 12), late adneomas (n = 12), Dukes's A and B carcinomas (n = 21), and Dukes's C and D carcinomas (n = 22) and compared these results with expression of these proteins in normal colonic mucosa (n = 17). A statistically significant trend of increasing expression was seen for both p53 (p < 0.005) and CD44 variant exon v6 (p < 0.0005) in subsequent stages of this tumour progression model. High expression of CD44 v5 was seen in most colorectal neoplasms (83%-96%), independent of stage. A statistically significant correlation was present between p53 expression and expression of variant v6 of CD44 (p < 0.01). Both p53 expression and CD44 v6 expression in adenomas increased with the degree of dysplasia (p < 0.05). The results of this study show that mutant p53 protein and variant v6 of the CD44 glycoprotein are markers of tumour progression in colorectal cancer.
结直肠癌的发生发展是通过一系列分子遗传学改变来实现的，这些改变为肿瘤进展提供了假定的标志物。本研究通过免疫组织化学方法，对早期腺瘤（n = 12）、晚期腺瘤（n = 12）、杜克氏A期和B期癌（n = 21）以及杜克氏C期和D期癌（n = 22）的组织样本进行研究，探讨肿瘤抑制基因p53的表达与细胞黏附分子CD44的剪接变体v5和v6之间的关系，并将这些结果与正常结肠黏膜（n = 17）中这些蛋白的表达进行比较。在该肿瘤进展模型的后续阶段，p53（p < 0.005）和CD44变体外显子v6（p < 0.0005）的表达均呈现出具有统计学意义的上升趋势。大多数结直肠肿瘤（83%-96%）中可见CD44 v5的高表达，且与分期无关。p53表达与CD44变体v6的表达之间存在统计学意义的相关性（p < 0.01）。腺瘤中p53表达和CD44 v6表达均随发育异常程度的增加而升高（p < 0.05）。本研究结果表明，突变型p53蛋白和CD44糖蛋白变体v6是结直肠癌肿瘤进展的标志物。
