Saetta Angelica A, Korkolopoulou Penelope, Karlou Maria, Levidou Georgia, Goudopoulou Athina, Thymara Irene, Stamatelli Angeliki, Tzivras Michalis, Michalopoulos Nikolaos V, Thomas-Tsagli Euphemia, Patsouris Efstratios
Department of Pathology, Medical School, National and Kapodistrian University of Athens, Greece.
Pathology. 2007 Aug;39(4):425-32. doi: 10.1080/00313020701444457.
The aim of this study was to determine the potential synchronous contribution of alterations in TGF-betaRII, BAX, IGFIIR, caspase-5, hMSH3 and hMSH6 genes to the development and clinical outcome of bladder cancer, in relation to p53 mutations, microsatellite status and hMLH1/hMSH2 expression.
Molecular biology techniques as well as immunohistochemistry were applied in 69 samples from patients with urothelial carcinoma.
Microsatellite alterations were observed in TGF-betaRII(A)(10 )(16%) and BAX(G)(8 )(3%), irrespective of the presence of p53 mutations, but not in IGFIIR(G)(8), caspase-5(A)(10, ) hMSH3(A)(8) and hMSH6(C)(8). A statistically significant correlation could be found only between hMLH1 expression and the presence of microsatellite instability (Fisher's exact test, p = 0,013). Survival analysis indicated that apart from grade and T-category, hMLH1 expression was the only parameter significantly affecting overall survival (p = 0.021 in univariate and p = 0.015 in multivariate analysis) and recurrence-free survival (p = 0.0463 in univariate and p = 0.022 in multivariate analysis).
We conclude that alterations of the examined target genes of MSI are rare in urinary bladder carcinoma and they are not associated with microsatellite instability or the presence of p53 mutations.
本研究旨在确定转化生长因子βⅡ型受体（TGF-βRII）、BAX、胰岛素样生长因子Ⅱ型受体（IGFIIR）、半胱天冬酶-5（caspase-5）、人错配修复蛋白3（hMSH3）和人错配修复蛋白6（hMSH6）基因改变与p53突变、微卫星状态及hMLH1/hMSH2表达相关时，对膀胱癌发生发展及临床结局的潜在同步影响。
对69例尿路上皮癌患者的样本应用分子生物学技术及免疫组织化学方法。
无论p53突变情况如何，在TGF-βRII（A）（10）（16%）和BAX（G）（8）（3%）中观察到微卫星改变，但在IGFIIR（G）（8）、caspase-5（A）（10）、hMSH3（A）（8）和hMSH6（C）（8）中未观察到。仅在hMLH1表达与微卫星不稳定性之间发现有统计学意义的相关性（Fisher精确检验，p = 0.013）。生存分析表明，除分级和T分期外，hMLH1表达是唯一显著影响总生存（单因素分析p = 0.021，多因素分析p = 0.015）和无复发生存（单因素分析p = 0.0463，多因素分析p = 0.022）的参数。
我们得出结论，微卫星不稳定性（MSI）相关的检测目标基因改变在膀胱癌中罕见，且它们与微卫星不稳定性或p53突变无关。
