Punyammalee B, Manoromana S, Purisa W, Chariyalertsak S, Rerkamnuaychok B
Research Division, National Cancer Institute, Department of Medical Services, Ministry of Public Health, Bangkok, Thailand.
J Med Assoc Thai. 1997 Sep;80 Suppl 1:S162-73.
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.
癌症的多药耐药性是癌症化疗中的主要问题之一，它常常与mdr1基因编码的P-糖蛋白（P-gp）的表达相关。然而，关于mdr1基因表达对乳腺癌细胞临床化疗耐药性的意义，存在有争议的结果。最近的证据报道，晚期乳腺癌中P-gp水平升高与预后密切相关。本研究调查了mdr1基因表达对乳腺癌患者预后及化疗反应是否有影响。我们采用基于逆转录-聚合酶链反应（RT-PCR）和非放射性标记探针的Southern印迹杂交检测的灵敏、特异且定量的技术，测定了127例原发性和8例局部复发性乳腺癌中的mdr1表达。在原发性乳腺癌患者中，mdr1表达阴性（mdr1-ve）、低表达（<10单位）、高表达（≥10单位）的患者分别占63.8%、8.7%和27.5%。mdr1阴性和阳性表达患者在年龄、绝经状态、肿瘤大小、分期、淋巴结受累情况、雌激素受体水平和p53水平方面未观察到差异。然而，mdr1基因表达常与阳性淋巴结数量和雌激素受体阴性相关（分别为p = 0.008和0.0007）。在局部复发病例中，mdr1阴性占62.5%，而37.5%为mdr1阳性且mdr1 RNA水平高。两组在其他预后因素：淋巴结受累情况、雌激素受体水平和p53水平方面未检测到差异。mdr1阴性和阳性患者在原发性和复发性乳腺癌中的化疗反应无差异。最后，我们的结果表明，mdr1基因表达在化疗前后的乳腺癌中均经常存在。mdr1基因过表达与其他两个预后因素的关联表明，它们可能赋予肿瘤更具侵袭性的特性、耐药性和不良预后。对这些因素的评估可能会提高识别和选择预后不良高风险乳腺癌患者进行积极治疗的能力。然而，在本系列中，原发性和局部复发性乳腺癌对CMF化疗的反应不受mdr1基因产物存在与否的影响。
