Association of mdrl Gene Expression with Other Prog- nostic Factors and Clinical Outcome in Human Breast Cancer
BOONNUM PUNY AMMALEE, D.Sc. * , WICHAI PURISA, B.Sc.*, SUPHON MANOROMANA, M.D.**, SUN ANT A CHARIY ALERTSAK, M.Sc. *, BUDS ABA RERKAMNUA YCHOK, D.M.Sc. ***
Affiliation : * Research Division, ** Division of Medical Oncology, National Cancer Institute, Department of Medical Services, Ministry of Public Health, Bangkok 10400, *** Department ofPathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
Abstract Multidrug resistance of cancer (CA) is one of a major problems in CA chemotherapy that is frequently associated with the expression of P-glycoprotein (P-gp) encoded by mdrl genes. However, the controversial results exist regarding to the significance of mdrl gene expression on clinical drug resistance to chemotherapy of breast CA cells. Recent evidence reported a strong correlation between the increased P-gp levels and the prognosis in advanced breast CA. The current study investigated whether mdrl gene expression has any impact on prognosis and response to chemotherapy in breast CA patients. We determined mdrl expression in 127 primary and 8 locally relapsed breast CA using a sensitive, specific and quantitative technique based on a RT- PCR and Southern blot hybridization detection by non-radioactive labelled-probe. In patients with primary breast CA, mdrl expression were negative (mdrl-ve), low (<10 units), high (~10 units) in 63.8, 8.7 and 27.5 per cent of the patients, respectively. No differences in age, menopause status, tumor size, stage, lymph node involvement, estrogen receptor level and p53 level were observed between mdrl-ve and mdrl+ve expression patients. However, mdrl gene expression is often associated with number of positive lymph nodes and negative estrogen receptors (p = 0.008 and 0.0007, respectively). In locally relapsed cases, mdrl-ve was 62.5 per cent whereas 37.5 per cent were mdrl +ve with high level of mdrl RNA. No differences in other prognostic factors: lymph nodal involvement, estrogen receptor level and p53 level, were detected in both groups. Response to chemotherapy in primary and recurrent breast CA was not different in mdrl-ve and mdrl+ve patients. Finally, our results show that mdrl gene expression is frequently present in breast CA both before and after chemotherapy. Association of mdrl gene overexpres- sion with other two prognostic factors suggests that they may confer a more aggressive nature of the tumor, drug resistance and poor prognosis. Evaluation of these factors may improve the ability to identify and select breast CA patients at high risk for poor prognosis for aggressive treatment. However, in this series response to CMF chemotherapy of primary and locally recurrent breast CA were not affected by the presence or absence of mdr 1 gene product.
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