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: 3731488
• 负责人: BARBARA S HULKA
• 金额: --
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3731488
• 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; 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PRAD1和蛋白质表达产物的扩增 可以独立或共同与组织病理学一起使用以改善 乳腺癌的预测能力。 该研究利用了来自6805名女性队列的手术标本 谁在蛋黄酱的非恶性乳腺疾病进行活检 从1967年1月1日至1981年12月31日，罗切斯特附属的医院。 遵循该队列直到1987年1月L，在此期间236例 发生了乳腺癌。不发展乳房的可比女性 在同一时间间隔内已选择癌症作为对照。这 研究的主要目标是：1。确定p53的频率 手术中的突变和相关免疫组织化学（IHC）标记 来自患有良性乳房疾病的女性的标本。 2。比较模式 配对良性和恶性的p53突变（以及相关的IHC标记） 组织。 3。确定是否从 p53阳性女性与p53负面女性不同 p53，HER-2和PRAD1的分子突变以及组织学外观 肿瘤。 4。确定是否在良性中选择了IHC标记 乳房疾病可能定义乳腺癌的风险。 5。确定是否 这些分子病变或IHC标记的存在与 组织学特征和流行病学风险因素是预测 最终进展为乳腺癌。 使用新型实验室技术检测分子病变 来自福尔马林固定的，石蜡包裹的部分的DNA少量DNA， 我们正在检查良性和恶性病变的组织。最近的 分析已检测到8％的良性乳房样品中的p53突变 经过测试，但没有在HER-2和PRAD1上进行基因扩增的证据 基因座。我们提出的研究将完成良性的分子分析 乳腺组织以p53为中心以及p53异常的后果 确定这些改变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 和良性乳腺疾病中的免疫组织化学标志物，并将评估 这些标记在识别有乳房高风险的女性方面的效用 癌症。