MOLECULAR/CELLULAR PREDICTORS OF BREAST CANCER PROGNOSIS

这一计划代表了一种多学科的方法 为乳腺癌开发新的预后指标。我们建议 乳腺癌的不同病程在很大程度上是 不同患者在细胞生物学上的根本差异 恶性上皮及其反应性间质。我们的理由是最近 利用模型系统进行分子和细胞生物学研究的进展即将到来 直接应用于问题。研究项目将集中在 四个领域：1)癌基因和受体激活，通过开发新的检测方法 提高c-erbB-2原癌基因的预后特异性 雌激素受体过表达与雌激素受体含量的调节机制 这些基因的异常表达；2)遗传异常，通过与 通过寻找新的基因突变和寻找新的基因突变水平来预测预后 基因异常表达影响预后；3)间期 细胞遗传学，利用荧光原位杂交技术评价 细胞遗传学异常在乳腺癌预后中的作用 间质-上皮细胞的相互作用，验证了癌症起源的假设 间质成纤维细胞通过以下途径促进乳腺癌的侵袭性 细胞外基质成分--透明质酸的过量生产。这个 该计划的临床核心将继续提供项目和其他 用外科乳房标本和细针抽吸材料制成的核心， 执行临床方案，并与 管理核心，提供临床数据和预期的随访 正在分析其肿瘤样本的所有患者的信息。这个 免疫病理学核心将优化免疫组织化学分析并评估 各种细胞抗原的预后意义。细胞培养 CORE将继续处理和储存分离的乳房组织样本， 并为研究项目提供培养细胞。细胞计量学和 生物统计核心将继续提供生物统计支持，以 维护所有相关数据的数据库，并进行细胞学和 细胞动力学分析。这些分子和细胞研究将被用于 优化和加强对活检材料进行的常规分析。 这些研究的结果将通过以下方式影响乳腺癌的存活率 改善预后指标，以及通过提供新的科学 对乳腺癌病理生理学的洞察。

This program represents a multidisciplinary approach save towards developing new prognostic indicators for breast cancer. We suggest that the variable course of breast cancer is in large part the result of fundamental differences among patients in the cellular biology of the malignant epithelium and its reactive stroma. Our rationale is that recent advances in molecular and cell biology using model systems are ready to be applied directly to the problem. The research projects will concentrate on four areas: 1) oncogene and receptor activation, by developing new assays to improve the prognostic specificity of c-erbB-2 proto-oncogene overexpression and estrogen receptor content based on mechanisms mediating the abnormal expression of these genes; 2) genetic aberrations, by relating prognosis to overall level of genetic aberrations and by searching for new genes whose aberrant expression affects prognosis; 3) interphase cytogenetics, utilizing fluorescence in situ hybridization to evaluate the role of cytogenetic abnormalities in breast cancer prognostication; and 4) stromal-epithelial interactions, testing the hypothesis that cancer-derived stromal fibroblasts contribute to breast cancer invasiveness via overproduction of the extracellular matrix component, hyaluronic acid. The Program's Clinical Core will continue to provide the projects and the other cores with surgical breast specimens and fine needle aspiration material, to conduct the clinical protocols and in association with the Administrative Core to provide clinical data and prospective follow-up information on all patients whose tumor samples are being analyzed. The Immunopathology Core will optimize immunohistochemical assays and evaluate the prognostic significance of various cellular antigens. The Cell Culture Core will continue to process and bank dissociated breast tissue specimens, and provide cultured cells for the research projects. The Cytometry and Biostatistics Core will continue to provide biostatistical support, to maintain a database of all relevant data, and to perform cytometric and cytokinetic analyses. These molecular and cellular studies will be used to optimize and augment the routine assays being performed on biopsy material. The results from these studies will impact on breast cancer survival by improving prognostic indicators, as well as by providing new scientific insights into breast cancer pathophysiology.