Association of mdr1 gene expression with other prognostic factors and clinical outcome in human breast cancer.
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 mdr1 genes. However, the controversial results exist regarding to the significance of mdr1 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 mdr1 gene expression has any impact on prognosis and response to chemotherapy in breast CA patients. We determined mdr1 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, mdr1 expression were negative (mdr1-ve), low (< 10 units), high (> or = 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 mdr1-ve and mdr1+ve expression patients. However, mdr1 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, mdr1-ve was 62.5 per cent whereas 37.5 per cent were mdr1+ve with high level of mdr1 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 mdr1-ve and mdr1+ve patients. Finally, our results show that mdr1 gene expression is frequently present in breast CA both before and after chemotherapy. Association of mdr1 gene overexpression 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 mdr1 gene product.
Punyammalee
B
B
Research Division, National Cancer Institute, Department of Medical Services, Ministry of Public Health, Bangkok, Thailand.
Manoromana
S
S
Purisa
W
W
Chariyalertsak
S
S
Rerkamnuaychok
B
B
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D019450:Genes, MDR; D006801:Humans; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics; D012680:Sensitivity and Specificity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012334:RNA, Neoplasm