Clinical Significance of p53 and bcl-2 Protein Coexpression Phenotypes in Molecular Breast Cancer Subtypes of Pre-menopausal and Post-menopausal African-American Women CHUKWUEMEKA U. IHEMELANDU, M.D., ROBERT L. DEWITTY, JR., M.D., LASALLE D. LEFFALL, JR., M.D., SIRAM M. SURYANARAYANA, M.D., WAYNE A. FREDERICK, M.D. From the Department of Surgery, Howard University College of Medicine, Washington, D.C With the current classification of breast carcinoma into molecular subtypes with distinct prog- nosis and response to therapy, we sort to assess the clinical significance of p53 and bcl-2 coex- pression phenotypes in invasive breast tumors and correlate this to the different molecular breast cancer subtypes in African-American women. We performed a retrospective analysis of data on p53 and bcl-2 expression. Results were correlated to molecular breast cancer subtypes, and clin- icopathologic variables of prognostic significance. Our study sample included all African- American women diagnosed with breast cancer from 1998 to 2005. Twenty-seven (27.6%) per cent of cases in our study sample over-expressed p53, whereas 69.3 per cent over-expressed bcl-2 protein. A significant inverse correlation was observed between expression of p53 and bcl-2. Combined analysis of p53 and bcl-2 showed that 53.2 per cent of the tumors displayed p53(2)bcl- 2(1) phenotype which was significantly associated with the luminal A subtype, whereas 11.6 per cent displayed the p53(1)bcl-2(2) phenotype which was significantly associated with the basal cell-like and Her-2/neu. Neither p53 expression nor bcl-2 expression individually or in combi- nation were of independent prognostic significance. p53(1)bcl-2(2) phenotype is significantly correlated with the basal cell-like subtype and may be associated with the biologic aggressiveness of this cohort of molecular breast cancer. P RESENTLY THERAPEUTIC decisions and prognostica- tion for breast cancer is formulated based on traditional clinico-pathological prognostic factors, however within these traditional staging groups exists molecular tumor subtypes with observed heterogeneity in recurrence rates and clinical responses to available therapies. Adjuvant therapy presently forms an integral part of the multimodal management of breast cancer in high risk patients. Of note is the fact that a significant number of women derive no benefit from the different chemotherapeutic regimens presently in use. Patients with basal-cell like (triple negative) breast cancer have an increased likelihood of distant metastasis, this despite these tumors being more chemosensitive than the other molecular subtypes. As we unravel the biology behind molecular breast cancer subtypes, the search for novel biological prognostic markers with which to complement existing staging systems has intensified, as these biological markers could be used to individualize patient stratification for adjuvant treatment. Immunohistochemical studies in breast cancer have tended to investigate expression of individual proteins in relation to prognosis, and relatively few studies have focused on the analysis of multiple markers in com- bination. However, one such combination which may be of value in breast cancer is the combined p53/bcl-2 phenotype, as suggested by Rolland et al., 1 who described the p53 positive/bcl-2 negative phenotype of 673 patients’ tumors, finding that this combination gave independent prognostic information. Apoptosis is Presented at the Annual Scientific Meeting and Postgraduate Course Program, Southeastern Surgical Congress, Atlanta, GA, February 7–10, 2009. Brief Statement: Understanding the role of p53/bcl-2 coex- pression phenotypes in molecular breast cancer subtypes may contribute to understanding the aggressive tumor behavior of the basal cell-like and Her-2/neu molecular subtypes and to identifying the subset of molecular breast cancers which may respond differ- ently to apoptotic stimuli from chemotherapy and radiotherapy. Address correspondence and reprint requests to Chukwuemeka U. Ihemelandu, Department of Surgery, Howard University Hos- pital, 2041 Georgia Avenue, N.W., Washington, D.C. 20060. E-mail: emeka_ihemelandu@hotmail.com or melands70@gmail. com. 776