Androgen Receptor as a Biomarker in Prostate Cancer Progression

描述（由申请人提供）： 前列腺癌是美国男性中最常见的癌症，被诊断患有这种疾病的男性面临着关于治疗的困难决定。随着PSA检测的出现，过去可能未被发现的肿瘤正在被诊断出来。医生们对一个男人应该接受的最合适的治疗缺乏统一的意见。积极的治疗（如根治性直肠切除术和放射治疗）可能提供最高的治愈可能性;但代价可能是性，泌尿和/或肠功能的损害。Gleason评分和诊断前PSA水平已被用作肿瘤侵袭性的预测因子，但它们不足以预测其肿瘤的长期侵袭性，特别是对于患有中等级别肿瘤的年轻男性。因此，需要更特异的生物标志物。一个有前途的研究领域涉及雄激素受体（AR）的表达水平。雄激素信号传导轴在前列腺的发育中很重要，并且与前列腺癌的风险以及疾病的进展相关。我们计划进行免疫组化，以测量AR表达在肿瘤和瘤周细胞在初步诊断时，并提取生殖系DNA从正常组织中分析CAG和GGC微卫星重复AR基因。这些生物标志物结果将与疾病进展、治疗和临床特征的指标相关联，并将通过多变量分析确定它们是否可以在添加到当前现有措施中时改善进展的预测。待研究的存档肿瘤组织先前已从1994-95年诊断为局部疾病并已随访进展至少5年的290名男性中获得。可获得关于其治疗、临床特征和复发/进展的信息（来自病历和自我报告的问卷）。样本包括140名白人，78名非洲裔美国人和72名西班牙裔美国人。根据自我报告，大约22%（65）的人取得了进展。样本量将允许检测到进展者和非进展者之间生物标志物患病率的20%差异以及低至2.5的进展风险增加。这项研究有助于帮助男性做出正确的治疗选择，改善长期生活质量，减少不必要的治疗。它也将为更大规模的研究奠定基础。

DESCRIPTION (provided by applicant): Prostate cancer is the most common cancer among men in the United States and men diagnosed with this disease are faced with a difficult decision regarding treatment. With the advent of PSA testing, tumors are being diagnosed that may have gone undetected in the past. There is a lack of uniform opinion among physicians on the most appropriate therapy a man should receive. Aggressive therapies (e.g. radical prostatectomy and radiation) may provide the highest likelihood of cure; but the cost may be an impairment of sexual, urinary, and/or bowel function. Gleason score and pre-diagnostic PSA levels have been used as predictors of tumor aggressiveness, but they are not sufficient, especially for younger men with an intermediate grade tumor, to predict the long term aggressiveness of their tumor. Therefore, more specific biomarkers are needed. One promising area of research concerns the level of androgen receptor (AR) expression. The androgen-signaling axis is important in the development of the prostate gland and is associated with risk of prostate cancer as well as with progression of disease. We plan to perform immunohistochemistry to measure AR expression in both tumor and peritumoral cells at the time of initial diagnosis and to extract germline DNA from normal tissue to assay CAG and GGC microsatellite repeats in the AR gene. These biomarker results will be linked with indicators of disease progression, therapy and clinical characteristics and it will be determined through multivariate analysis if they can improve the prediction of progression when added to currently existing measures. The archived tumor tissue to be studied has been previously obtained from 290 men who were diagnosed with localized disease in 1994-95 and have been followed for progression for at least 5 years. Information is available on their therapy, clinical characteristics, and recurrence/progression (from medical records and self-reported questionnaires). The sample includes 140 whites, 78 African-Americans, and 72 Hispanics. Based on self-reports, about 22% (65) have progressed. The sample size will permit differences of 20% in prevalence of a biomarker between the progressors and nonprogressors to be detected as well as an increased risk of progression as low as 2.5. This study has implications for assisting men in making the right treatment choice, improving long-term quality of life, and reducing unnecessary therapy. It will also lay the groundwork for larger studies examining.