PROGRESSION FROM BENIGN BREAST DISEASE TO BREAST CANCER--IMMUNOHISTOCHEMISTRY

我们设计了一项研究来检测分子变化(P53突变 和HER-2/neu和PRAD1的扩增)和蛋白质表达产物 可单独或与组织病理学联合服务以改善 对乳腺癌的预测能力。 这项研究使用了来自6805名女性队列的手术标本 谁在梅奥接受了非恶性乳腺疾病的活检？ 从1967年1月1日到1981年12月31日，罗切斯特附属医院。 队列追踪至1987年1月L，其间有236例 乳腺癌的发病率为100%。未发育乳房的可比女性 选择同一时间间隔内的癌症作为对照。这个 本研究的主要目的是：1.确定P53基因的频率 外科手术中的突变和相关免疫组织化学(IHC)标记 来自患有良性乳腺疾病的妇女的样本。2.比较模式 P53基因突变(及相关IHC标记物)在配对的良、恶性病变中的表达 纸巾。3.确定后续出现的肿瘤是否 P53阳性女性与P53阴性女性在以下方面存在差异 P53、HER-2和PRAD1的分子突变及其组织学表现 肿瘤的最新进展。4.确定选定的IHC标志物在良性疾病中是否 乳房疾病可能会定义乳腺癌的风险。5.确定是否 这些分子病变或IHC标志物的存在，结合 组织学特征和流行病学危险因素具有预测性 最终发展成乳腺癌的可能性。 使用新的实验室技术检测分子损伤 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。近期 分析发现8%的良性乳腺样本中存在P53基因突变 检测，但没有证据表明HER-2和PRAD1基因扩增 精神错乱。我们提出的研究将完成良性疾病的分子分析 以P53为中心的乳腺组织及P53异常的后果 确定这些变化是否预示着随后的发展 乳腺癌。这项研究将提供关于基因的作用的信息 和免疫组织化学标记物在良性乳腺疾病中的应用 这些标记物在识别乳房高危女性中的作用 癌症。

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.