Search for molecular marker for predicting progression in prostate cancer by competitive PCR analysis

前列腺癌在可能致命的人类恶性肿瘤中是独一无二的，因为各国在死亡率和发病率方面存在显著差异。环境因素和肿瘤进展所必需的遗传事件发生概率的差异可能是导致癌细胞增殖的因素。然而，尽管有这些考虑，前列腺癌发生的分子机制仍知之甚少。在我们之前的研究中，我们使用基于pcr的微卫星不稳定性试验筛选了66例前列腺癌患者5条染色体上8个微卫星标记位点的可能突变表型。66例患者中有13例（19.7%）检测到不稳定微卫星。躯体不稳定性可能与一种能够侵入前列腺外的表型有关。我们没有发现肿瘤的体积、分布或DNA倍体状态与西方对照有明显差异。对29例人前列腺癌雄激素受体（AR）基因结构异常进行了检测。在1例（3.4%）激素非依赖性D2期患者中，发现AR外显子D激素结合域发生点突变，导致629密码子上谷氨酰胺（CAG）取代野生型精氨酸（CGG）。27例患者中有5例（18.5%）、6例激素不依赖型D2期患者中有1例（16.7%）、21例激素依赖和未治疗的前列腺癌患者中有4例（19.0%）检测到微卫星不稳定。采用竞争PCR法进一步研究kai-1、bcl2、tgf - β和PTHrP在人前列腺癌组织中的表达规律。没有确定具体的表达模式。

Prostate cancer is unique among potentially lethal human malignancies in terms of striking differences in the mortality rate and incidence according to country. Environmental factors and differences in the probability of occurrence in genetic events essential for tumor progression may possibly be factors responsible for cancer cell proliferation. However, molecular mechanisms for prostate carcinogenesis is very little understood despite these considerations. The PCR-based microsatellite instability assay was used to screen 66 patients with prostatic adenocarcinoma for possible mutator phenotype at 8 microsatellite marker loci on 5 chromosomes in our previous study. Unstable microsatellites was detected in 13 of the 66 (19.7%) patients. Somatic instability may be related to a phenotype with the ability to invade outside the confines of the prostate gland. We could not find any distinct differences in volume, distribution or DNA ploidy status of a tumor from western counterpart. Examination was made of structural abnormality of the androgen receptor (AR) gene in 29 human prostate cancer. A point mutation was found in the exon D hormone-binding domain of AR leading to substitution of glutamine (CAG) for wild-type arginine (CGG) at codon 629 in 1 (3.4%) hormone-independent stage D2 patient. Microsatellite instability was detected in 5 of the 27 (18.5%)patients, 1 of 6 (16.7%) hormon independent stage D2 and 4 of 2l (19.0%) hormdne-dependent and non-treated prostate cancer patients. Competitive PCR method was employed to further investigate the pattern of expression of kai-1, bcl2, TGFbeta and PTHrP in human prostate cancer. No specific pattern of expression was determined.