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一个艰难的治疗决定。随着PSA检测的出现，过去可能未被发现的肿瘤被诊断出来。医生们对男性应该接受的最合适的治疗缺乏统一的意见。积极治疗（如根治性前列腺切除术和放疗）可能提供最高的治愈可能性；但其代价可能是性功能、排尿功能和/或肠道功能受损。Gleason评分和诊断前PSA水平已被用作肿瘤侵袭性的预测指标，但它们并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。一个有前景的研究领域涉及雄激素受体（AR）表达水平。雄激素信号轴在前列腺的发育中很重要，与前列腺癌的风险以及疾病的进展有关。我们计划在初始诊断时进行免疫组织化学检测AR在肿瘤和肿瘤周围细胞中的表达，并从正常组织中提取种系DNA以检测AR基因中的CAG和GGC微卫星重复序列。这些生物标志物的结果将与疾病进展、治疗和临床特征的指标联系起来，并将通过多变量分析确定，如果将它们添加到现有的措施中，是否可以改善对进展的预测。待研究的存档肿瘤组织来自于1994- 1995年间被诊断为局限性疾病的290名男性，并随访了至少5年。可获得有关其治疗、临床特征和复发/进展的信息（来自医疗记录和自我报告的问卷）。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，约22%（65人）进展。样本量将允许在进展者和非进展者之间检测到20%的生物标志物患病率差异，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，提高长期生活质量，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.