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

Fonseca FL, Sant Ana AV, Bendit I, Arias V, Costa LJ, Pinhal AA, del Giglio A - Breast Cancer Res. (2004)

Bottom Line: In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity.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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: ABC Foundation School of Medicine, Hematology and Oncology, Santo Andre, São Paulo, Brazil. ge.fonseca@uol.com.br

ABSTRACT

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.

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Correlations between microsatellite instability (MSI) events, treatment, and hMSH2-positive cells. Significant correlations between (a) number of MSI events and type of treatment received by patients during which samples were collected (2, alkylating chemotherapy; 3, nonalkylating chemotherapy; 4, radiation therapy; 5, hormone therapy; and 6, off treatment), (b) percentage of hMSH2-positive cells and number of MSI events (MSI and loss of heterozygosity [LOH]), and (c) percentage of hMSH2-positive cells and type of treatment received by patients during which samples were collected (1, before treatment; 2, alkylating chemotherapy; 3, nonalkylating chemotherapy; 4, radiation therapy; 5, hormone therapy; 6, off treatment). Values are expressed as means and standard errors (for P values see text).
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Figure 2: Correlations between microsatellite instability (MSI) events, treatment, and hMSH2-positive cells. Significant correlations between (a) number of MSI events and type of treatment received by patients during which samples were collected (2, alkylating chemotherapy; 3, nonalkylating chemotherapy; 4, radiation therapy; 5, hormone therapy; and 6, off treatment), (b) percentage of hMSH2-positive cells and number of MSI events (MSI and loss of heterozygosity [LOH]), and (c) percentage of hMSH2-positive cells and type of treatment received by patients during which samples were collected (1, before treatment; 2, alkylating chemotherapy; 3, nonalkylating chemotherapy; 4, radiation therapy; 5, hormone therapy; 6, off treatment). Values are expressed as means and standard errors (for P values see text).

Mentions: We observed a significant correlation between the number of MSI events per sample and the use of chemotherapy (P = 0.005), especially chemotherapy containing alkylating agents (P < 0.0001; Fig. 2). We also observed an inverse correlation between the number of MSI events per sample and the percentage of cells positive for MSH2 by immunocytochemistry (P = 0.00019) and especially for the MFD41 marker (P = 0.000638). The percentage of cells positive for MSH2 by immunocytochemistry was inversely correlated with the use of chemotherapy regimens containing alkylating agents (P = 0.019). We found no significant correlations between the number of MSI events or the presence of LOH and the frequency of cells positive for TP53, hMLH1, hPMS1 and hPMS2.


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

Fonseca FL, Sant Ana AV, Bendit I, Arias V, Costa LJ, Pinhal AA, del Giglio A - Breast Cancer Res. (2004)

Correlations between microsatellite instability (MSI) events, treatment, and hMSH2-positive cells. Significant correlations between (a) number of MSI events and type of treatment received by patients during which samples were collected (2, alkylating chemotherapy; 3, nonalkylating chemotherapy; 4, radiation therapy; 5, hormone therapy; and 6, off treatment), (b) percentage of hMSH2-positive cells and number of MSI events (MSI and loss of heterozygosity [LOH]), and (c) percentage of hMSH2-positive cells and type of treatment received by patients during which samples were collected (1, before treatment; 2, alkylating chemotherapy; 3, nonalkylating chemotherapy; 4, radiation therapy; 5, hormone therapy; 6, off treatment). Values are expressed as means and standard errors (for P values see text).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064099&req=5

Figure 2: Correlations between microsatellite instability (MSI) events, treatment, and hMSH2-positive cells. Significant correlations between (a) number of MSI events and type of treatment received by patients during which samples were collected (2, alkylating chemotherapy; 3, nonalkylating chemotherapy; 4, radiation therapy; 5, hormone therapy; and 6, off treatment), (b) percentage of hMSH2-positive cells and number of MSI events (MSI and loss of heterozygosity [LOH]), and (c) percentage of hMSH2-positive cells and type of treatment received by patients during which samples were collected (1, before treatment; 2, alkylating chemotherapy; 3, nonalkylating chemotherapy; 4, radiation therapy; 5, hormone therapy; 6, off treatment). Values are expressed as means and standard errors (for P values see text).
Mentions: We observed a significant correlation between the number of MSI events per sample and the use of chemotherapy (P = 0.005), especially chemotherapy containing alkylating agents (P < 0.0001; Fig. 2). We also observed an inverse correlation between the number of MSI events per sample and the percentage of cells positive for MSH2 by immunocytochemistry (P = 0.00019) and especially for the MFD41 marker (P = 0.000638). The percentage of cells positive for MSH2 by immunocytochemistry was inversely correlated with the use of chemotherapy regimens containing alkylating agents (P = 0.019). We found no significant correlations between the number of MSI events or the presence of LOH and the frequency of cells positive for TP53, hMLH1, hPMS1 and hPMS2.

Bottom Line: In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity.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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: ABC Foundation School of Medicine, Hematology and Oncology, Santo Andre, São Paulo, Brazil. ge.fonseca@uol.com.br

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus