Jansson Agneta, Arbman Gunnar, Zhang Hong, Sun Xiao-Feng
Division of Oncology, Department of Biomedicine and Surgery, Linköping University, S-581 85 Linköping, Sweden.
Int J Oncol. 2003 Jan;22(1):41-9.
We examined biological and clinicopathological significance of individual and combined hMLH1, hMSH2, hMSH3 and hMSH6 expression with immunohistochemistry in 301 unselected colorectal cancers. Weak hMLH1 expression was correlated to microsatellite instability (P=0.04), negative p53 expression (P=0.005) and mucinous carcinomas (P=0.02). Weak hMSH2 expression was related to negative ras (P<0.001) and p53 expression (P=0.005), and better survival (P=0.03). hMSH2, hMSH3 and hMSH6, as well as hMLH1, hMSH2, hMSH3 and hMSH6, were combined into a 'functional' and a 'less-functional' group, respectively. Both 'less-functional' groups were/tended to be associated with microsatellite instability, negative ras and p53 expression, and better survival. In summary, hMLH1 and hMSH2 were more important when investigated individually, and the combined groups were more related to the mutator pathway, suggesting that combined deficiencies of the proteins are more efficiently involved in the mutator pathway. Our result from weak versus strong staining may suggest that the intensity of staining should be considered in future studies on mismatch repair proteins.
我们采用免疫组织化学方法检测了301例未经选择的结直肠癌中hMLH1、hMSH2、hMSH3和hMSH6单独及联合表达的生物学和临床病理意义。hMLH1弱表达与微卫星不稳定性（P=0.04）、p53阴性表达（P=0.005）及黏液腺癌（P=0.02）相关。hMSH2弱表达与ras阴性（P<0.001）、p53表达阴性（P=0.005）及较好的生存率（P=0.03）相关。hMSH2、hMSH3和hMSH6以及hMLH1、hMSH2、hMSH3和hMSH6分别被组合成一个“功能正常”组和一个“功能较差”组。两个“功能较差”组均/倾向于与微卫星不稳定性、ras和p53阴性表达及较好的生存率相关。总之，单独研究时hMLH1和hMSH2更为重要，而组合组与错配修复缺陷途径的相关性更强，提示蛋白质的联合缺陷更有效地参与错配修复缺陷途径。我们关于弱染色与强染色的结果可能提示，在未来对错配修复蛋白的研究中应考虑染色强度。
