Association of p53 Protein Expression With Tumor Cell Proliferation Rate and Clinical Outcome in Node-Negative Breast Cancer

作者：Donald Craig Allred, Gary M. Clark, Richard M. Elledge, Suzanne A.W. Fuqua, Richard W. Brown, Gary C. Chamness, Charles Kent Osborne, William Leo McGuire · 发表于：JNCI Journal of the National Cancer Institute · 年份：1993 · DOI：10.1093/jnci/85.3.200 · 被引用次数：784 · 研究领域：Cancer-related Molecular Pathways、Biological Research and Disease Studies、Cancer Research and Treatments

BACKGROUND: The p53 (also known as TP53) tumor suppressor gene encodes for a nuclear phosphoprotein thought to regulate proliferation of normal cells. Most p53 mutations result in a nonfunctional protein that accumulates in tumor cell nuclei. These common mutations appear to be involved in the development and/or progression of several neoplastic diseases including human breast cancer. PURPOSE: Our purpose was to investigate the relationships between levels of mutant p53 protein expression, tumor cell proliferation rate, and clinical outcome in patients with node-negative breast cancer. METHODS: Expression of mutant p53 protein was evaluated by frozen-section immunohistochemistry (IHC) and light microscopy in 700 breast cancers from axillary lymph node-negative patients with long-term follow-up (median, 54 months). The immunostaining signal was expressed as the sum of scores representing the proportion and staining intensity of negative and positive tumor cell nuclei (ranges, 0 and 2-8, respectively). Statistical comparisons were made between levels of p53 protein expression and disease-free survival, overall survival, and tumor proliferation rate expressed as the percentage of cells in the S phase (%S phase) as determined by flow cytometry. RESULTS: Of the 700 tumors, 362 (52%) showed positive nuclear immunostaining (IHC score > 0). Proliferation rates were significantly higher (P = .0001) in positive tumors (median %S phase, 7.1%) than in negative tumors (4.1%). In a univari...