PREMALIGNANT LESIONS OF THE PROSTATE--AGE AND RACE STUDY

前列腺癌(PCA)是我国最常见的恶性肿瘤。 美国男性，占所有与癌症相关的男性的13% 死亡。非洲裔美国人(AA)男性的发病率高出50%， 罹患癌症的死亡率是高加索人的两倍 (C)。造成这种差异的原因(S)不得而知。可以查看PCA 包括两种主要形式。潜伏性癌症，定义为已发现的癌症 巧合的是，在没有临床证据的情况下， 流行，早在第三个十年就可以确定和表现出来 没有记录在案的患病率种族差异。临床癌症，定义 因为那些已经引起临床注意的人明显较少 比潜伏性PCA常见，表现出不同的进展速度，并且 与地理、种族和种族差异有关的发病率和 死亡率。主成分分析的前体定义不明确。从形态上讲很好 高级别前列腺上皮内瘤变的特征性实体 (HGPIN)已显示出与临床的强烈流行病学联系 诊断形式的前列腺癌。我们的数据显示HGPIN在 年龄在30岁到70岁以上的男性，AA多于C。此外，广泛的 弥漫性累及腺体的HGPIN在AA男性中比C男性更常见 同样的年龄，广泛的HGPIN在AA中出现的时间大约早了十年 而不是C个雄性。我们还观察到缺乏解剖学联系。 HGPIN与大多数(67%)青年男性潜伏性前列腺癌之间的关系 5))两个种族的。 与此相似的AA男性患者的临床PCa发生率显著更高 潜伏性前列腺癌的流行表明其他一些因素(S)是 造成这种临床差异的原因。两种可能的解释是 (1)HGPIN在AA男性中更为常见和广泛，并且是遗传的 与C男性相比不稳定，2)潜伏期比例更高 AA患者中与HGPIN解剖相关的PCa可能更有可能进展 一种临床症状明显的疾病。 这些假设将使用传统的整体安装进行测试。 对分步切开的整个前列腺进行组织病理学检查。那 与50岁年龄组的C组男性相比，AA患者的HGPIN更为广泛。 65年，临床诊断为前列腺癌之前的时间跨度将为 确认了。AA中的HGPIN越广泛，评估的结果就越好 通过研究肿瘤丢失的频率来研究遗传不稳定性 抑癌基因位于8号染色体短臂(8p22)。损失 这一基因座的缺失已被记录为前列腺癌的常见事件 致癌。肿瘤侵袭性等生物标志物较大 体积、分化较低的组织学、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是 学习。预计这些参数在AA和 C男人将为提出的假设提供强有力的支持，并将 导致对观察到的流行病学有更好的了解 不同种族之间主成分分析的差异。

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.