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记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。这些病变与正常或癌组织的基因表达谱分析将为前列腺癌的病因学提供重要线索，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滞后于前列腺癌发展后期的密集分子表征。我们的长期目标是研究人类前列腺中所有潜在的癌症前驱病变，并牢固地建立癌症起始的分子决定因素。我们的总体假设是，在癌症发生和发展之前的组织学变化可以通过签名表达谱来定义，而签名表达谱反过来又反映了多种遗传和环境因素导致的分子改变。本探索性研究将重点关注人类高级别前列腺上皮内瘤变（HGPIN）的分子特征和分类，HGPIN是最可能的前列腺癌前体病变，旨在确定与临床定义的人类前列腺癌相关的癌前前列腺标志物。我们将利用成熟的cDNA微阵列技术，通过与侵袭性前列腺癌和正常前列腺上皮病变的比较，系统地分析60个HGPIN标本。具体而言，我们计划在2年内实现以下目标：(1)定义HGPIN的分子特征，并确定所有HGPIN病变共同或HGPIN亚群特有的推定癌前前列腺标志物。(2)对HGPIN病变中已知前列腺癌/侵袭标志物和候选癌前标志物进行免疫组化分析。

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.