THIOESTERASE 11 A NEW BREAST CANCER MARKER

硫酯酶II是一种关键酶，它调节 通过水解中链酰基在乳腺中的中链脂肪酸 脂肪酸合成酶的硫酯键部分。 我们的研究 与大鼠和人类的研究表明，硫酯酶II表达 仅在乳腺上皮细胞中，观察结果与其 在牛奶脂肪合成中的作用 在人体内可检测到免疫反应酶 乳腺上皮细胞，无论其分化状态如何， 在乳腺上皮起源的原发性和转移性肿瘤中也是如此; 酶在其他细胞类型中检测不到。 动物实验 肿瘤模型显示硫酯酶II存在于大鼠血清中 患有乳腺上皮肿瘤，但在正常血清中检测不到; 血清中的浓度与肿瘤负荷成比例。 这些结果 表明该酶可能是鉴定 乳腺上皮起源的人类肿瘤。 本研究有两个目的：（1）检验 免疫组化硫酯酶染色鉴定， 人类乳腺肿瘤的分类;（2）确定是否 硫酯酶II也被释放到携带 乳腺上皮性肿瘤，并评估血清检测在 人乳腺癌诊断。 因此，为了实现这些目标，我们将 制备单克隆抗人硫酯酶抗体， 免疫组织化学和酶联免疫测定方法。 在 与几位病理学家合作，我们将优化 免疫组织化学试验，并将评估的特异性和有效性 不同类型和级别的原发性乳腺肿瘤的硫酯酶染色 和乳腺癌转移瘤的检测。 我们将使用 动物肿瘤模型和最终的人类患者，以确定血清是否 硫酯酶水平显示出与肿瘤负荷的可靠相关性， 是否能达到一个便于使用的灵敏度水平 在人类乳腺癌的早期诊断、预后和随访中。 （一）

Thioesterase II is a key enzyme which regulates the production of medium-chain fatty acids in mammary gland by hydrolyzing medium-chain acyl moieties from thioester linkage to the fatty acid synthetase. Our studies with rats and humans have shown that thioesterase II is expressed exclusively in mammary epithelial cells, an observation consistent with its role in milk fat synthesis. Immunoreactive enzyme can be detected in human breast epithelial cells regardless of their state of differentiation and also in both primary and metstatic tumors of breast epithelial origin; the enzyme is undetectable in other cell types. Experiments with an animal tumor model have shown that thioesterase II is present in the serum of rats bearing a mammary epithelial tumor but is undetectable in normal serum; the concentration in serum is proportional to tumor burden. These results indicate that the enzyme may be a useful marker for the identification of human tumors of breast epithelial origin. There are two objectives for this study: (1)\to test the utility of immunohistochemical thioesterase staining in the identification and classification of human breast tumors; (2)\to determine whether thioesterase II is also released into the serum of human patients bearing mammary epithelial tumors and to evaluate the potential of serum testing in human breast cancer diagnosis. Thus, in pursuit of these aims, we will prepare monoclonal anti-human thioesterase antibodies for use in both immunohistochemical and enzyme-linked immunoassay procedures. In collaboration with several pathologists, we will optimize the immunohistochemical test and will evaluate the specificity and efficacy of thioesterase staining in primary breast tumors of various types and grades and detection of metastatic tumors of breast carcinomas. We will use an animal tumor model and eventually human patients to determine whether serum thioesterase levels show a reliable correlation with tumor burden and whether a level of sensitivity can be achieved which would facilitate use in the early diagnosis, prognosis, and followup of human breast cancer. (1)