CYTOGENETICS AND BIOCHEMISTRY OF PROSTATE CANCER

这是对RFA CA-91-10的回应，是以下方面的合作： 细胞遗传学、医学、分子生物学、病理学和泌尿学。 前列腺癌（PCA）是最常诊断的浸润性癌症， 是美国男性癌症死亡的第二大常见原因。 是 在黑人和年龄增长的受试者中发病率增加。 黑人的生存期更短。临床过程从迅速 通常在诊断后10-20年对存活者是致命的。 大多数PCA 只有在尸检时才发现。 大多数在生活中诊断出的PCA是或变成 症状，并可能导致严重的疼痛，从转移到骨， PCA的70-80%。 存活时间可能很长，有或没有严重的症状， 甚至在发现转移瘤多年后。 有很大 需要能够预测哪些PCA将进展缓慢，哪些将 进展迅速，即，可以更好地遵循没有侵略性 疗法 我们的目标是精确鉴定 不同的亚群 最常见的预测因素是 临床表现是组织病理学分化。 更强大的 需要预测;这可能需要一种定性的方法， 与目前使用的不同（希望是互补的） 预测器 我们想从细胞遗传学和分子遗传学的角度 畸变，这将是有用的更精确的预后指标。 过去，实现这一目标的一个重要障碍是， PCA细胞在体内和体外增殖中遇到的困难， 体外 最近，我们报道了一种方法，用于传播一个大的 无胸腺动物中原发性PCA的比例。 我们已经 连续移植异种移植物。这允许扩展可用的 肿瘤，一个有用的方法来采购恶性PCA细胞免费 良性上皮细胞和人基质细胞的研究， 在一段时间内用许多技术培养出可行的PCA细胞。 我们也 有方法，使短期文化的五氯苯甲醚充分 用于细胞遗传学分析。 我们将尝试将几个临床 参数与实验参数。 常规临床参数 我们的中心包括种族，年龄，Gleason分级，超声图像， 疾病，转移调查，术前及术后血清前列腺特异性抗原 手术后间隔，患者中可测量肿瘤的生长速率， 至疾病复发的时间和生存期（总体和疾病 具体）。 实验参数的相关性和评价如下： 可能是重要的预测因子，既可以作为单个参数，也可以作为多个 补充参数包括格里森模式（量化的 形态测定法），肿瘤大小（形态测定法定量），倍性， 细胞遗传学畸变（常规畸变和原位荧光畸变 杂交）。免疫缺陷动物的生长速度， 选择的肿瘤抑制基因的突变和蛋白质表达 以及所选生长因子及其受体的基因扩增。

This is a response to RFA CA-91-10 and is a collaboration among cytogenetics, medicine, molecular biology, pathology, and urology. Prostate cancer (PCA) is the most commonly diagnosed invasive cancer and the second most common cause of cancer deaths in US males. It is increased in incidence among blacks and among increasingly aged subjects. Survival is shorter among blacks. The clinical course ranges from rapidly fatal to survival often 10-20 years after diagnosis. Most PCA is discovered only at autopsy. Most PCA diagnosed during life is or becomes symptomatic and may result in severe pain from metastases to bone in up to 70-80% of PCA. Survival may be long, with or without severe symptoms, even many years after the identification of metastases. There is a great need to be able to predict which PCAs will progress slowly and which will progress rapidly, i.e., may be better followed without aggressive therapy. Our goal is the precise identification of biologically different subpopulations. The most commonly recognized predictor of clinical behavior is histopathological differentiation. A more powerful predictor is needed; this may require an approach that is qualitatively different from (hopefully complementary to) the currently employed predictors. We want to identify cytogenetic and molecular genetic aberrations that will be useful as more precise prognostic indicators. An important obstacle to this goal in the past has been the exceptional difficulty encountered in the propagation of PCA cells both in vivo and in vitro. Recently, we reported a method for the propagation of a large proportion of primary PCAs in athymic animals. We have since transplanted xenografts serially. This permits expansion of the available tumor, a useful approach to the procurement of malignant PCA cells free of benign epithelial cells and human stromal cells, and the study of viable PCA cells with many techniques over the course of time. We also have methods that have permitted the short-term culture of PCA adequate for cytogenetic analyses. We shall attempt to correlate several clinical parameters with experimental parameters. Clinical parameters routine in our center include race, age, Gleason grade, ultrasound image, stage of disease, metastatic survey, serum prostate specific antigen before and at intervals after surgery, rate of growth of measurable tumors in patients, time to recurrence of disease, and survival (both total and disease specific). Experimental parameters to be correlated and evaluated as possibly important predictors both as single parameters and as multiple complementary parameters include Gleason patterns (quantified morphometrically), size of tumor (quantified morphometrically), ploidy, cytogenetic aberrations (both conventional and by fluorescence in situ hybridization). rate of growth in immunodeficient animals, the loss and mutation of selected tumor suppressor genes, and the protein expression and gene amplification of selected growth factors and their receptors.