Prtilo Alexandra, Leach Fredrick S, Markwalder Regula, Kappeler Andreas, Burkhard Fiona C, Cecchini Marco G, Studer Urs E, Thalmann George N
Urology Research Laboratory, Department of Urology, University of Bern, Inselspital, Bern, Switzerland.
J Urol. 2005 Nov;174(5):1814-8; discussion 1818. doi: 10.1097/01.ju.0000176796.47988.64.
Mismatch repair genes are responsible for the coordinated correction of misincorporated nucleotides formed during DNA replication. Mismatch repair expression is altered in a subset of prostate cancers (PCs) and a recent study suggested that time to biochemical recurrence following prostatectomy correlated with the degree of hMSH2 immunohistochemical staining. We compared hMSH2 expression and survival in clinically organ confined PC.
A prostate tissue microarray was constructed using 243 specimens from patients who underwent radical prostatectomy with extended lymph node dissection for clinically organ confined PC with up to 12 years of followup. Immunohistochemistry was performed with anti-human MSH2 monoclonal antibody. Three independent observers evaluated hMSH2 expression on a scale of 0 to 4. Low expression was defined as a score of less than 2 and high expression was defined as a score of 2 or higher. Statistical analysis used the Fisher exact test, and Goodman and Kruskal gamma coefficient.
Higher Gleason score significantly correlated with higher hMSH2 expression (p < 0.0002). Low hMSH2 expression correlated with increased overall, disease-free and biochemical disease-free survival (all p < 0.01). Analysis comparing low vs high hMSH2 expression was significant with respect to overall (p = 0.0004), disease-free (p = 0.005) and biochemical disease-free (p = 0.0177) survival.
hMSH2 is differentially expressed in malignant prostate tissue and hMSH2 immunohistochemical staining intensity correlates with Gleason score, overall and disease-free survival. Taken together our results suggest that hMSH2 expression may be a useful prognostic biomarker for outcome in men with clinically organ confined PC.
错配修复基因负责协调纠正DNA复制过程中形成的错配核苷酸。错配修复表达在一部分前列腺癌（PC）中发生改变，最近一项研究表明前列腺切除术后生化复发时间与hMSH2免疫组化染色程度相关。我们比较了临床局限于器官的PC中hMSH2的表达与生存率。
使用243例接受根治性前列腺切除术并扩大淋巴结清扫术的临床局限于器官的PC患者的标本构建前列腺组织微阵列，随访时间长达12年。用抗人MSH2单克隆抗体进行免疫组化。三名独立观察者以0至4分的标准评估hMSH2表达。低表达定义为评分小于2分，高表达定义为评分2分或更高。统计分析采用Fisher精确检验和Goodman与Kruskalγ系数。
较高的Gleason评分与较高的hMSH2表达显著相关（p < 0.0002）。低hMSH2表达与总体生存率、无病生存率和生化无病生存率的提高相关（所有p < 0.01）。比较低hMSH2表达与高hMSH2表达的分析在总体生存率（p = 0.0004）、无病生存率（p = 0.005）和生化无病生存率（p = 0.0177）方面具有显著性。
hMSH2在恶性前列腺组织中差异表达，hMSH2免疫组化染色强度与Gleason评分、总体生存率和无病生存率相关。综合我们的结果表明，hMSH2表达可能是临床局限于器官的PC男性患者预后的有用生物标志物。
