MDR1 and thymidylate synthase (TS) gene expressions in advanced breast cancer: relationships to drug exposure, p53 mutations, and clinical outcome of the patients.
MDR1 and thymidylate synthase (TS) gene expressions in advanced breast cancer: relationships to drug exposure, p53 mutations, and clinical outcome of the patients.
复制标题
晚期乳腺癌中的 MDR1 和胸苷酸合酶 (TS) 基因表达：与药物暴露、p53 突变和患者临床结果的关系。
作者：
S. Lizard‐Nacol;P. Genne;B. Coudert;J. Riedinger;M. Arnal;C. Sancy;P. Brunet‐Lecomte;P. Fargeot
为了描述与化疗反应差和预后差相关的晚期乳腺癌的生物学特征，对75例接受初次化疗的患者的连续肿瘤样本进行了治疗前后MDR 1和TS基因表达的分析。同时分析了36例正常人的MDR 1基因表达情况。采用逆转录-聚合酶链反应（RT-PCR）方法检测MDR 1和TS基因表达水平，并与p53基因状态及临床预后进行相关性分析。治疗后，肿瘤（p = 0.0033）和正常（p = 0.0098）样本中MDR 1表达水平显著增强，而TS表达显著降低（p = 0.0054）。MDR 1或TS表达与p53突变（24%的病例中检测到）、化疗反应性或生存率之间无显著相关性。只有p53突变与无病生存率降低相关（p = 0.0473）。这些结果表明，MDR 1和TS基因表达受药物暴露的影响，但不受p53基因状态。此外，MDR 1基因在正常和肿瘤组织中表达的增加有利于诱导的MDR 1表达，而不是选择耐药肿瘤克隆，这可能是导致MDR 1表达与晚期乳腺癌患者临床结局之间缺乏相关性的原因。
To characterize the biological features of advanced breast cancer associated with poor chemotherapy response and worse prognosis, sequential tumor samples obtained from 75 patients receiving primary chemotherapy were analysed for MDR1 and TS gene expression before and after treatment. MDR1 gene expression was also analysed in 36 sequential normal samples. The levels of MDR1 and TS genes expression were determined by reverse transcription-PCR method, and examined in relation to p53 gene status, and the clinical outcome of the patients. After treatment, MDR1 expression levels were significantly enhanced in tumor (p = 0.0033) and normal (p = 0.0098) samples, whereas a significant decrease in TS expression was observed (p = 0.0054). There was no significant correlation between MDR1 or TS expressions and the presence of p53 mutations (detected in 24% of the cases), chemoresponsiveness, or survival. Only p53 mutations were associated with reduced disease-free survival (p = 0.0473). These results demonstrate that MDR1 and TS gene expressions were affected by drug exposure, but not by p53 gene status. Furthermore, the increase of MDR1 gene expression in normal and tumor tissues is in favor of an induced MDR1 expression rather than of a selection of resistant tumoral clones, which can be responsible for the absence of relationship of MDR1 expression with clinical outcome of advanced breast cancer patients.