DNA STUDIES & P53 GENE ABNORMALITIES IN PROSTATE CANCER

被诊断为前列腺癌(CAP)的患者数量 在过去的七年里增长了63%。在同一时间段内， 死亡人数从每年的24,000例增加到32,000例。使用 美国男性人口老龄化和避孕药使用量增加 筛选上限，这些数字只能预计在未来几年内上升 未来几年。尽管目前有越来越多的患者 被诊断为局限性CAP，AFP的恶性潜能 单个肿瘤不能用目前的情况准确地确定 方法论。没有定义或识别恶性的 肿瘤的潜在性，临床研究人员无法 将处于休眠状态的癌症与将处于休眠状态的癌症区分开来 进步和竞争是导致死亡的原因。适用于需要 治疗，目前的知识也缺乏，使临床医生 预测他们的肿瘤是否会对放射治疗有反应。如果一个 肿瘤恶性潜能的准确标志物被发现，患者 可以提供一种更合理的治疗方法，在许多情况下 案例，将意味着单独观察。 目前，有两个标记物在这两个领域都显示出希望，即肿瘤。 P53基因的倍性和突变。这些标志物还没有被 在一项大型的多机构研究中进行了评估。这项提议将 正在进行的CAP患者的倍体和P53的研究 临床试验(INT-0086/SWOG-8794)。符合条件的患者将会是 在根治性前列腺切除术后发现边缘阳性，因此 疾病进展的可能性很高。在这项试验中，患者是 随机分为观察组或辅助放射治疗组。有用性 然后将使用558个样本对这些标记进行评估 来自这一大型多机构试验的患者。 本提案的具体目标包括：1)评估 前列腺活检DNA倍体的临床应用；2) 确定阳性边缘的倍性是否可以预测临床 结果；3)确定倍性是否是更强的预测因子 结果比患者是否接受辅助放射治疗更重要； 4)确定肿瘤的P53状态是否准确 预测恶性潜能和对放射治疗的反应；以及 5)评价是否能确定卵巢癌细胞的倍体和P53状态 肿瘤提供了附加信息。的有用性的确定 CAP中的这些标记可能是合理化和 局限型帽子患者的个体化治疗。

The number of patients diagnosed with prostate cancer (CaP) has increased 63% in the last seven years. Over the same time period, the number of deaths has risen from 24,000 to 32,000 cases a year. With the aging of the American male population and the increased use of screening for CaP, these figures can only be expected to rise over the coming years. Although increased numbers of patients are currently being diagnosed with localized CaP, the malignant potential of an individual tumor cannot be accurately determined with present methodology. Without definition or identification of the malignant potential of the tumor, clinical investigators are unable to distinguish the cancers that will remain dormant from those that will progress and compete as a cause of mortality. For patients who require therapy, current knowledge is also lacking to allow clinicians to predict whether their tumor will respond to radiation therapy. If an accurate marker of tumors malignant potential were found, patients could be offered a more rational approach to therapy that, in many cases, would mean observation alone. Presently, two markers show promise in both these areas, namely tumor ploidy and mutation in the p53 gene. These markers have not yet been evaluated in a large, multi-institutional study. This proposal will study ploidy and p53 in patients with CaP who are entered on an ongoing clinical trial (INT-0086/SWOG-8794). Eligible patients will have been found to be margin positive after radical prostatectomy and thus have a high likelihood of disease progression. In this trial, patients are randomized to observation or adjuvant radiation therapy. The usefulness of these markers will then be evaluated utilizing specimens of 558 patients from this large multi-institutional trial. Specific aims of this proposal include the following: 1) to evaluate the clinical usefulness of DNA ploidy of a prostate biopsies; 2) to determine whether the ploidy of the positive margins predicts clinical outcome; 3) to determine whether ploidy is a stronger predictor of outcome than whether the patient receives adjuvant radiation therapy; 4) to determine whether the p53 status of the tumor is an accurate predictor of malignant potential and response to radiation therapy; and 5) to evaluate whether determining the ploidy and p53 status of the tumor gives additive information. Determination of the usefulness of these markers in CaP may be an initial step in the rationalization and individualization of treatment of patients with localized CaP.