Premalignant Prostate Markers That Forebode Malignancy

描述(由申请人提供)：描述前列腺癌前病变的分子标志物特征对于有效控制和管理高度流行的人类前列腺癌至关重要。这些病变与正常组织或癌组织的基因表达谱将为前列腺癌的病因提供重要线索，并有助于制定新的预防策略和早期检测方法。然而，临床标本中假定的前驱病变的系统基因表达分析落后于前列腺癌发展后期密集的分子特征。我们的长期目标是调查人类前列腺癌中所有潜在的癌症前驱病变，并坚定地确定癌症发生的分子决定因素。我们的总体假设是，在癌症发生和发展之前以及导致癌症发生和发展的组织学变化可以通过签字人的表达谱来定义，这反过来又反映了多种遗传和环境因素造成的分子变化。这项探索性研究将集中在人类高级别前列腺上皮内瘤变(HGPIN)的分子特征和分类上，HGPIN是前列腺癌最有可能的前驱病变，旨在寻找与临床定义的人类前列腺癌相关的癌前标志物。我们将利用成熟的基因芯片技术系统地分析60个HGPIN样本，并与代表浸润性前列腺癌和正常前列腺上皮的病变进行比较。具体地说，我们计划在两年内实现以下目标：(1)定义HGPIN的分子特征，并识别所有HGPIN病变共同的或HGPIN亚组独有的可能的癌前前列腺癌标志物。(2)对HGPIN病变中已知的前列腺癌/侵袭标志物和候选癌前标志物进行免疫组织化学分析。

DESCRIPTION (provided by applicant): Delineation of molecular markers characteristic of premalignant prostate lesions is critically important to effectively control and manage the highly prevalent human prostate cancer. Gene expression profiling of these lesions in relation to normal or cancerous tissues will provide important clues to the etiology of prostate carcinogenesis and help to formulate novel prevention strategies and early detection methods. Systematic gene expression analysis of putative precursor lesions in clinical specimens, however, is lagging behind the intensive molecular characterization in later stages of prostate cancer development. Our long-term goal is to investigate all potential cancer precursor lesions in the human prostate gland and firmly establish the molecular determinants of cancer initiation. Our overall hypothesis is that histological changes preceding, and leading to cancer initiation and progression can be defined by signatory expression profiles, which in turn reflect molecular alterations as a result of multiple genetic and environmental factors. This exploratory study will focus on the molecular characterization and classification of human high-grade prostatic intraepithelial neoplasia (HGPIN), the most probable precursor lesion to prostate cancer, in an effort to identify premalignant prostate markers associated with clinically defined human prostate cancer. We will take advantage of the well-established cDNA microarray technology to systematically profile 60 HGPIN specimens by comparison to lesions representing invasive prostate cancer and normal prostate epithelium. Specifically, we set out to achieve the following Aims in 2 years: (1) To define the molecular signature of HGPIN and identify putative premalignant prostate markers common to all HGPIN lesions or unique to subgroups of HGPIN. (2) To perform immunohistochemical analysis of known prostate cancer/invasion markers and candidate premalignant markers in HGPIN lesions.