Breast stem cell analysis in random periareolar fine needle aspirates from high r

描述(由申请人提供)： 乳腺癌通常被认为是由一小部分干细胞或祖细胞引起的，这些干细胞或祖细胞对致癌物特别敏感。乳腺干细胞是一种长寿的细胞，主要是静止的细胞，能够在体内重新繁殖退化的乳腺，并在体外优先扩张。乳腺干细胞对乳腺癌风险的贡献尚未得到证实，但这些细胞被认为是乳腺癌发生的中心。这项研究的目的是通过一项将干细胞标记物与乳腺细胞形态和组织形态(乳腺癌风险的组织测量)相关联的先导性研究，建立一种方法来量化和表征乳腺癌高危女性乳晕周围细针抽吸(RPFNA)样本中的干细胞。我们的中心假设是，乳腺干细胞数量的增加增加了患乳腺癌的风险。这项工作将提供一种新的乳腺癌风险测量方法，并通过以下具体目标为乳腺癌预防提供一种更有针对性的方法：目的1：确定良性乳腺疾病与乳腺干细胞流行之间的相关性。我们的工作假设是，乳腺干细胞数量的增加会增加乳腺癌的风险，这将与早期和中期乳腺疾病(伴有非典型性增生、小叶或导管原位癌，已知的高风险标记)的患病率增加有关。将使用免疫组织化学和实时聚合酶链式反应对干细胞标记物进行评估。这项工作在使用RPFNA评估乳腺干细胞种群以及干细胞和良性乳腺疾病的检查方面是新颖的。总体而言，这项工作有可能提高我们对乳腺干细胞和癌症风险的理解，并通过一种新的干细胞靶向方法来完善乳腺癌预防。

DESCRIPTION (provided by applicant): Breast cancer is thought to arise frequently from a small population of stem or progenitor cells that are particularly susceptible to carcinogens. Breast stem cells are long-lived, mostly quiescent cells that are capable of repopulating involuted mammary glands in vivo and expanding preferentially in vitro. The contribution of breast stem cells to breast cancer risk is unproven, but these cells are thought to be central to breast carcinogenesis. The objective of this study is to establish the methodology to quantify and characterize stem cells in random periareolar fine needle aspiration (RPFNA) samples of breast tissue from women at high risk for breast cancer through a pilot study correlating stem cell markers with breast cytomorphology and histomorphology (tissue- based measures of breast cancer risk). Our central hypothesis is that increased numbers of breast stem cells confer elevated risk for the development of breast cancer. This work will provide a novel measure of breast cancer risk and a more targeted approach for breast cancer prevention through the following specific aim: Aim 1: Determine the correlation between benign breast disease and the prevalence of breast stem cells. Our working hypothesis is that increased numbers of breast stem cells elevate the risk of breast cancer and this will be associated with increased prevalence of early and intermediate breast disease (hyperplasia with atypia , lobular or ductal carcinoma in situ, known markers of elevated risk). Evaluation of stem cell markers by immunohistochemistry and real time PCR of RPFNA and biopsy samples will be used. This work is novel in the use of RPFNA to evaluate breast stem cell populations and examination of stem cells and benign breast disease. Overall, this work has the potential to improve our understanding of breast stem cells and cancer risk and refine breast cancer prevention through a novel stem cell-targeted approach.