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- W4246572083 abstract "9628 Background: Despite the consistent improvement in overall survival afforded by systemic adjuvant chemotherapy, about 1% of Breast Cancer (BC) patients develop secondary leukemias and/or myelodisplasia probably as a consequence of the genotoxic effects of this type of treatment. Methods: In order to evaluate if systemic chemotherapy could produce microsatelite instability (MSI), we studied 119 sequential blood samples from 30 previously untreated BC patients, collected at every three months intervals, before, during and after receiving systemic chemotherapy. After PCR amplification of the extracted DNA with specific primers for 6 microsatelite loci (BAT-26, BAT-40, MFD-28, MFD-41, TP53, PCR15.1, tp53ALU), the PCR products were denatured, subjected to SSCP and for microssatelite instability (MSI) and loss of heterozigocity (LOH). We also evaluated the expression of PCNA, hMLH1, hPMS1, hPMS2, hMSH2 and P-53 proteins in the PBMC by immunocytochemistry. Results: We observed MSI in 40 of the 119 samples and 27 out of 30 patients had MSI observed in at least one of their collected samples. We observed appearance of LOH at the PCR15.1 locus in 6 patients. We observed a significant correlation between the number of MSI events per sample and the use of chemotherapy ( p = 0.005) specially if it contained alquilating agents (p < 0.0001) . We also observed an inverse correlation between the number of MSI events per sample and the percentage of positive cells for MSH2 by immunocytochemistry (p = 0,0001). The percentage of positive MSH2 cells by immunocytochemistry was inversely correlated with the use of chemotherapy regimens containing alquilating agents (p = 0.019). Conclusions: We conclude that alquilating agent chemotherapy may induce MSI and LOH in PBMC from BC patients possibly through chemotherapy induced decrease in the expression of MSH2. These findings may be related to the generation of secondary leukemias and may also contribute to the intensification of the genetic instability of tumors and further resistance to treatment. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration FAPESP" @default.
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- W4246572083 date "2004-07-15" @default.
- W4246572083 modified "2023-09-25" @default.
- W4246572083 title "Microsatellite instability (MSI) and loss of heterozigocity (LOH) in the peripheral blood mononuclear cells (PBMC) of breast cancer (BC) patients receiving systemic chemotherapy" @default.
- W4246572083 doi "https://doi.org/10.1200/jco.2004.22.14_suppl.9628" @default.
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