Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients

Breast Cancer Research

Auro del Giglio³  Aparecida A Pinhal⁵  Luciano J Costa¹  Vitor Arias⁴  Israel Bendit²  Aleksandra VL Sant Ana³  Fernando LA Fonseca³ 

[1] Faculdade de Medicina da Universidade de São Paulo, Pathology Post Graduate Section, São Paulo, Brazil;Hemocentro de São Paulo, Tumor Biology, São Paulo, Brazil;Faculdade de Medicina da Universidade de São Paulo, Hematology Post Graduate Section, São Paulo, Brazil;Instituto Adolfo Lutz, Anatomic Pathology, São Paulo, Brazil;ABC Foundation School of Medicine, Biochemistry, São Paulo, Brazil

关键词: second primary;    proliferating cell nuclear antigen;    neoplasms;    microsatellite repeats;    cyclophosphamide;   

Others  :  1122727
DOI  :  10.1186/bcr950

 received in 2004-05-13, accepted in 2004-09-24,  发布年份 2004

【 摘 要 】

Introduction

Systemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients.

Methods

We studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group).

Results

In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019).

Conclusion

We conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment.

【 授权许可】

   
2004 Fonseca et al., licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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