Investigation on molecular markers for assessment of biological activity in prostate cancer

尸检研究中经常发现临床上无症状的前列腺癌，这表明一些男性有良性的自然病史，但在另一些男性中，前列腺癌的侵袭性更强，可能是致命的。为了确定进展的分子标记，研究了微卫星重复序列的基因组不稳定性、DNA倍体状态和血清转化生长因子β1水平对预测更具侵袭性的表型的作用。对66例前列腺癌患者进行了5条染色体8个微卫星标记座位的体细胞不稳定性筛查。13例(19.7%)患者存在基因组不稳定性。在控制了其他临床病理变量后，发现腺外扩散与躯体不稳定性显著相关。提示基于聚合酶链式反应的微卫星不稳定性分析可作为前列腺癌的分子预后标志物。应用核图像分析技术，对70例前列腺癌根治术标本的每一癌灶进行DNA倍体分析。在103例个体癌中，(62%)为非二倍体。DNA倍体与肿瘤体积增大呈弱相关，与肿瘤分级无关。DNA倍体与前列腺外扩散的关系无统计学意义。260例前列腺癌患者血清转化生长因子β1水平与肿瘤分级、分期相关。在这些变量之间没有发现相关性。

The frequent detection of clinically silent prostate cancer in autopsy studies suggests a benign natural history of the disease in some men, but more aggressive and potentially lethal cancers in others. In order to determine molecular markers for progression, genomic instability of microsatellites repeats, DNA ploidy status and serum transforming growth factor beta 1 levels were investigated for their usefulness to predict more aggressive phenotype. Sixty-six patients with prostate adenocarcinoma were screened for somatic instability at 8 microsatellite marker loci on 5 chromosomes. Genomic instability was detected in 13 (19.7%) patients. Extraglandular spread was found to show significant association with somatic instability after controlling for other clinicopathological variables. It was suggested that polymerase chain reaction based microsatellite instability assay may serve as a useful molecular prognostic marker in prostate cancer. DNA ploidy of each focus of a cancer in 70 radical prostatectomy specimens was determined by nuclear image analysis. Of the 103 individual cancers, 64 (62%) were nondiploid. DNA ploidy was weakly correlated with increase in tumor volume but not tumor grade. The relationship between DNA ploidy and extraprostatic spread was not statistically significant. Serum levels of transforming growth factor beta 1 were correlated with tumor grade and stage in 260 patients with prostate cancer. There was no correlation seen between these variables