PROGRESSION FROM BENIGN BREAST DISEASE TO BREAST CANCER--IMMUNOHISTOCHEMISTRY

从良性乳腺疾病到乳腺癌的进展--免疫组织化学

• 批准号: 6356225
• 负责人: Barbara S Hulka
• 金额: $ 16.85万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-05 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6356225
• 关键词: DNA; biopsy; breast neoplasms; cancer risk; female; gene expression; gene frequency; gene mutation; genetic markers; histopathology; human data; human genetic material tag; human tissue; mammary disorder; molecular biology; natural gene amplification; neoplasm /cancer epidemiology; neoplasm /cancer genetics; p53 gene /protein; polymerase chain reaction; single strand conformation polymorphism; tumor suppressor genes

We have designed a study to detect molecular alterations (p53 mutations and amplifications of HER-2/neu and PRAD1) and protein expression products that may serve independently or jointly with histopathology to improve predictive capability for breast cancer. The study utilizes surgical specimens derived from a cohort of 6805 women who underwent biopsy for non-malignant breast disease at the Mayo Rochester-affiliated hospitals from January 1, 1967, to December 31, 1981. The cohort was followed until January l, 1987, during which time 236 cases of breast cancer occurred. Comparable women who did not develop breast cancer during the same interval have been selected as controls. The primary objectives of the study are: 1. To determine the frequency of p53 mutations and related immunohistochemical (IHC) markers in surgical specimens from women with benign breast disease. 2. To compare the pattern of p53 mutations (and related IHC markers) in paired benign and malignant tissues. 3. To determine whether the subsequent tumors that emerge from p53 positive women differ from p53 negative women in the profile of molecular mutations at p53, HER-2, and PRAD1, and in histologic appearance of the tumors. 4. To determine whether selected IHC markers in benign breast disease may define breast cancer risk. 5. To determine if the presence of these molecular lesions or IHC markers, in conjunction with histologic characteristics and epidemiologic risk factors, is predictive of eventual progression to breast cancer. Using novel laboratory techniques for detecting molecular lesions in minute quantities of DNA from formalin-fixed, paraffin-embedded sections, we are examining tissues from both benign and malignant lesions. Recent analyses have detected p53 mutations in 8% of the benign breast samples tested, but no evidence of gene amplification at the HER-2 and the PRAD1 loci. Our proposed study will complete the molecular analysis of benign breast tissue centering on p53 and consequences of p53 abnormalities to determine if these alterations predict the subsequent development of breast cancer. This study will provide information on the role of genetic and immunohistochemical markers in benign breast disease and will evaluate the utility of these markers in identifying women at high risk of breast cancer.

我们设计了一项研究，以检测分子改变（p53突变 HER-2/neu和PRAD 1的扩增）和蛋白质表达产物 其可以独立地或与组织病理学联合地用于改善 乳腺癌的预测能力。 该研究使用了来自6805名女性的手术标本 她在马约医院接受了非恶性乳腺疾病的活检 罗切斯特附属医院从1967年1月1日至1981年12月31日。 队列随访至1987年1月1日，在此期间， 发生了乳腺癌。未发育乳房的可比女性 在相同的时间间隔内的癌症被选择作为对照。的 本研究的主要目的是：1.为了确定p53的频率 基因突变和相关免疫组化（IHC）标记物在外科手术中的应用 来自患有良性乳腺疾病的女性的标本。2.为了比较 配对良性和恶性肿瘤中p53突变（和相关的IHC标记物） 组织中3.为了确定是否随后出现的肿瘤， p53阳性妇女与p53阴性妇女在以下方面存在差异： p53、HER-2和PRAD 1的分子突变，以及组织学表现 肿瘤。4.为了确定所选的IHC标志物是否为良性肿瘤， 乳腺疾病可以定义乳腺癌的风险。5.以确定是否 这些分子病变或IHC标志物的存在，以及 组织学特征和流行病学危险因素，是预测 最终发展为乳腺癌的可能性 使用新的实验室技术检测 从福尔马林固定的石蜡包埋切片中提取微量DNA， 我们正在检查良性和恶性病变的组织。最近 分析已经在8%的良性乳腺样本中检测到p53突变， 测试，但没有证据表明HER-2和PRAD 1基因扩增 的位点我们提出的研究将完成良性肿瘤的分子分析。 以p53为中心的乳腺组织和p53异常的后果， 确定这些变化是否预测了随后的发展， 乳腺癌这项研究将提供有关遗传作用的信息， 和免疫组化标记物，并将评估 这些标记物在识别乳腺癌高危女性中的效用 癌