MOLECULAR MARKERS FOR HIGH RISK OF BREAST CANCER

这些研究的主要目标是开发预测 导管原位癌(DCIS)病例将复发和/或侵袭到 协助乳房X光检查发现的DCIS的临床处理。去做 我们将检查单纯DCIS和与侵袭性DCIS相关的DCIS的病例 一系列已知的分子和免疫组织化学标记物的癌症 在浸润性癌症中表现异常。包括在标记中的标记 评估的是杂合性丢失(LOH)和基因扩增 不同的染色体位点，不同的免疫组织化学标记 与侵袭性以及与失调相关的标志物 增殖和凋亡。 第二个目标是进行初步研究，以识别分子 非恶性上皮中可能区分这些病例的标志物 很可能会发展成癌症。这些研究将集中在 形态上非恶性乳腺上皮的特征 与恶性肿瘤相邻，将此组织与真正正常的乳房进行比较 上皮和患者的其他组织(即皮肤与乳房 上皮细胞)。如果这些研究成功地识别了分子 恶性肿瘤旁非恶性上皮中的异常现象 超出提案范围的研究可以评估标记物的效果 当与其他诊断程序结合使用时，用于早期诊断 检查方式如针吸和/或随机乳头活检。 此外，这些标记物可能在化学预防试验中替代 目前使用的恶性肿瘤终点将允许试验 患者较少，时间较短。

The major goal of these studies is to develop markers predictive of which ductal carcinoma in situ (DCIS) cases will recur and/or become invasive to aid in the clinical management of mammographically-detected DCIS. To do this we will examine cases of pure DCIS and DCIS associated with invasive cancers for a number of molecular and immunohistochemical markers known to be abnormal in invasive cancers. Included among the markers to be evaluated are loss of heterozygosity (LOH) and gene amplification at various chromosomal loci, various immunohistochemical markers associated with invasion as well as markers associated with dysregulated proliferation and apoptosis. A second goal is to undertake preliminary studies to identify molecular markers in nonmalignant epithelium that might distinguish those cases likely to progress to cancer. These studies will concentrate on characterizing the morphologically nonmalignant mammary epithelium adjacent to malignancies, comparing this tissue to truly normal mammary epithelium and to other tissues of the patient (i.e., skin vs. mammary epithelium). If these studies are successful in identifying molecular aberrations in nonmalignant epithelium adjacent to malignancy, future studies beyond the scope of the proposal could evaluate marker efficacy for early diagnosis when used in combination with other diagnostic modalities such as needle aspirates and/or random nipple biopsies. Additionally, such markers mabe surrogates in chemoprevention trials for the currently used endpoint of malignancy which would allow trials to be performed with fewer patients and over shorter time periods.