MITOSIN A NEW PROLIFERATION MARKER FOR CANCER DIAGNOSIS

乳腺癌的诊断给患者和临床医生提出了几个难题，如是否在手术后使用全身辅助治疗。如果临床医生在诊断时就能掌握患者肿瘤的分子指纹，从而准确预测复发和治疗反应，那么对这类患者的管理将得到优化。因此，在组织学分级系统中，细胞增殖已被用作监测疾病状态的有丝分裂指标；然而，这种方法执行起来很繁琐。较新的方法，如DNA流式细胞术，已被用于将s期细胞分数与原发性乳腺癌患者的临床结果联系起来。流式细胞术设备的费用、技术的普遍标准化以及结果的可重复性问题限制了其作为临床标准预后因素的接受程度。最近，有丝分裂蛋白，一种350 kda的核磷酸化蛋白，被证实参与有丝分裂期的进程。初步结果表明免疫组织化学染色丝裂蛋白与s期分数直接相关，与疾病早期复发相关。为了研究有丝分裂蛋白作为预后指标的价值，我们将开发适用于有丝分裂蛋白免疫组化染色的单克隆抗体。这些研究将在临床样本中提供对丝裂蛋白预后意义的基本理解，这将导致人类乳腺癌诊断测试和治疗的发展。建议的商业应用：开发临床有用的单克隆抗体，适用于有丝分裂蛋白的免疫组织化学染色，这将取代昂贵和繁琐的流式细胞术分析，作为原发性乳腺癌的预后因素。我们将开发抗体，将工作，并在各种固定程序和染色技术下给出一致的结果。这将导致一种简单、廉价的诊断测试的发展，这种测试将提供给较小的、非学术治疗中心的乳腺癌患者。

Diagnosis of breast cancer presents several dilemmas for patients and clinicians such as whether or not to use systemic adjuvant therapy following surgery. Management of such patients would be optimized if clinicians had a molecular fingerprint of a patient's tumor at the time of diagnosis that would accurately predict recurrence and treatment responses. As such, cell proliferation has been used as a mitotic index to monitor disease status in histologic grading systems; however, this approach is tedious to perform. Newer methods such as DNA flow cytometry have been used to correlate S-phase fraction of cells with clinical outcomes of patients with primary breast cancer. The expense of flow cytometry equipment, universal standardization of techniques and questions about reproducibility of results has limited its acceptance as a standard prognostic factor in the clinic. Recently, it has been shown that mitosin, a 350-kDa nuclear phosphoprotein, is specifically involved in mitotic phase progression. Preliminary results demonstrate that mitosin staining by immunohistochemistry is directly related to S-phase fraction and associated with early disease recurrence. In order to study the value of mitosin as a prognostic indicator we will develop monoclonal antibodies suitable for immunohistochemical staining of mitosin. These studies will provide the basic understanding of the prognostic significance of mitosin, in clinical samples that will lead to development of diagnostic test and treatment of human breast cancer. PROPOSED COMMERCIAL APPLICATIONS: Development of clinically useful monoclonal antibodies suitable for immunohistochemical staining of mitosin which will serve to replace expensive and tedious flow cytometry analysis of S-phase fraction as a prognostic factor for primary breast cancer. We will develop antibodies that will work and give consistent results under a wide variety of fixation procedures and staining techniques. This will lead to development of a simple, inexpensive diagnostic test, which will be available to breast cancer patients in smaller, non-academic treatment centers.