乳腺癌系统化疗与微卫星不稳定性的关系

Correlation between systemic chemotherapy and microsatellite instability in patients with breast cancer

目的探讨乳腺癌全身化疗与周围血微卫星不稳定的关系。方法应用PCR和免疫组化测定30例乳腺癌患者化疗前、中、后周围血单核细胞,并与正常组进行对照比较。结果90%(27/30)患者化疗后周围血中发现微卫星不稳定(microsatellitein-stability,MSI),其中6例出现杂合子丢失(lossofheterozygosity,LOH)。MSI与化疗明显相关;MSI与hMSH2呈负相关;hMSH2与治疗方法明显相关;MSI与p53、hMLH1、hPMS1和hPMS2不相关。结论化疗可导致患者周围血单核细胞MSI和LOH发生,且可能与hMSH2表达有关,从而导致部分患者发生继发血液系统异常,以及导致肿瘤基因的不稳定和增加化疗的耐药。

OBJECTIVE： To evaluant the correlation between systemic chemotherapy and microsatellite instability （MSI） in the peripheral blood mononuelear cells of breast cancer patients, METHODS： Blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy were detected by PCR and immunoeytoehemistry assay and were compared with control group. RESULTS; 90% （27/30） patients were observed MSI at last one sample, and six had loss of heterozygosity. There was significant correlation between the number of MSI per sample and chemotherapy, with alkylating agents. There was an inverse correlation between the percentage of positive cells of hMSH2 and the MSI and the use of alkylating agents. There were no correlation between MSI and p53, hMLH1, hPMS1, and hPMS2. CONCLUSIONS： Systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients who received alkylating agent, which possibly mediated by the expression of hMSH2. These events may be related to the generation of secondary leukaemia in some patients, and also may intensity the genetic instability of tumours and increase resistance of chemotherapy.