PREMALIGNANT LESIONS OF THE PROSTATE--AGE AND RACE STUDY

前列腺癌（PCa）是最常见的诊断恶性肿瘤， 美国男性，占所有男性癌症相关疾病的13% 死亡 非洲裔美国人（AA）男性的发病率高出50%， 与白种人相比， （C）. 这种差异的原因尚不清楚。 可以查看PCa 包括两种主要形式。 潜伏性癌症，定义为那些发现 在没有临床证据表明患有PCa的男性中， 普遍，可以确定，早在第三个十年的生活和显示 患病率无记录的种族差异。 临床癌症，已定义 与那些已经引起临床关注的相比， 比潜伏性PCa常见，显示不同的进展率， 与地理、种族和人种的发病率差异有关， mortality. 前列腺癌的前体定义不明确。 一个形态上的井 称为高级别前列腺上皮内瘤变的特征性实体 （HGPIN）已显示出与临床 诊断为前列腺癌。 我们的数据显示，HGPIN在以下人群中更为普遍： 30至70岁以上的AA男性多于C男性。 此外，广泛 HGPIN弥漫性累及腺体在AA男性比C男性更常见， 与AA中大约十年前出现的广泛HGPIN相同的年龄 比C男性多。 我们还观察到， HGPIN与年轻男性（年龄以下）中的大多数（67%）潜伏性PCa之间的关系 5))两个种族。 AA男性中临床PCa的发生率明显较高， 潜伏性PCa的患病率表明， 造成了这种临床差异 两种可能的解释是 （1）HGPIN在AA男性中更常见和广泛，并且在遗传上是 不稳定相比，C男子，和2），更高比例的潜在的 AA男性中与HGPIN解剖学相关的PCa可能更有可能进展 临床表现的疾病 这些假设将使用传统的整体安装进行测试 对阶梯切片的整个前列腺进行组织病理学检查。 的 HGPIN在50岁以下的AA男性中比C型男性更广泛， 65年，临床诊断PCa之前的时间跨度将是 确认 将评估AA中更广泛的HGPIN， 遗传不稳定性通过研究肿瘤丢失的频率 抑制基因位于第8号染色体短臂（8p22）。 损失 该位点的突变已被证明是前列腺疾病中的常见事件。 致癌作用 肿瘤侵袭性的生物标志物，如较大的 体积、低分化组织学、非整倍体肿瘤DNA含量和 更高的增殖率和血管生成活性也将 研究了 预计这些参数在AA和 C人将为提出的假设提供强有力的支持， 更好地了解观察到的流行病学 种族间PCa的差异。

Prostatic carcinoma (PCa) is the most commonly diagnosed malignancy in American males and is responsible for 13% of all male cancer-related deaths. African-American (AA) males have a 50% higher incidence and suffer twice the mortality rates due to this cancer compared to Caucasians (C). The reason(s) for this difference are not known. PCa can be viewed as encompassing two major forms. Latent cancers, defined as those found incidently in men without clinical evidence of having PCa, are extremely prevalent, can be identified as early as the third decade of life and show no documented racial difference in prevalence. Clinical cancers, defined as those which have come to clinical attention, are significantly less common than latent PCa, show variable rates of progression and are associated with geographic, ethnic and racial differences in incidence and mortality. Precursors of PCa are poorly defined. A morphologically well characterized entity termed high grade prostatic intraepithelial neoplasia (HGPIN) has shown strong epidemiologic association with the clinically diagnosed form of PCa. Our data has shown HGPIN to be more prevalent in AA than C males between 30 and 70+ years of age. Furthermore, extensive HGPIN diffusely involving the gland is more common in AA than C males of the same ages with extensive HGPIN appearing about a decade earlier in AA than C males. We have also observed a lack of anatomic association between HGPIN and the majority (67%) of latent PCa in young men (under age 5)) of both races. The significantly higher incidence of clinical PCa in AA men with similar prevalence of latent PCa indicates that some other factor(s) are responsible for this clinical discrepancy. Two possible explanations are that (1) HGPIN is more common and extensive in AA males and is genetically unstable as compared to C men, and 2) that a higher proportion of latent PCa anatomically related to HGPIN in AA men may be more likely to progress to a clinically manifest disease. These hypotheses will be tested using conventional whole mount histopathology performed on step-sectioned entire prostate glands. That HGPIN is more extensive in AA compared to C males in the age group of 50- 65 years, the time span preceding clinically diagnosed PCa will be confirmed. The more extensive HGPIN in AA will be evaluated for greater genetic instability by studying the frequency of loss of a tumor suppressor gene located on the short arm of chromosome 8 (8p22). The loss of this locus has been documented to be a frequent event in prostatic carcinogenesis. Biological markers of tumor aggressiveness such as larger volume, less differentiated histology, aneuploid tumor DNA content and higher rates of proliferation and angiogenic activity will also be studied. It is expected that the valuation of these parameters in AA and C men will provide strong support for the hypothesis presented and will lead to a greater understanding of the observed epidemiological differences in PCa between races.