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.
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.
