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Microsatellite instability analysis of bilateral breast tumors suggests treatment-related origin of some contralateral malignancies

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Abstract

Purpose

High-frequency microsatellite instability (MSI-H) occurs frequently in colorectal cancers and some other tumor types, but is very uncommon in breast cancer. In the earlier study devoted to microsatellite analysis of allelic imbalances, the authors accidentally detected several MSI-H tumors in patients with the bilateral form of breast cancer (biBC). The present study was designed to examine this unexpected phenomenon in more detail.

Methods

All DNA samples were tested by the standard panel of MSI-specific markers BAT25, BAT26, BAT40, D5S346, and D17S250. If the tumor was unstable for at least one marker, or PCR amplification was not successful for any of the listed above loci, the analysis of additional five dinucleotide markers (D1S225, D11S4167, D22S272, D22S1166, and D3S3527) was performed. Tumors showing instability in ≥30% loci were classified as MSI-H.

Results

In biBC group, MSI-H status was detected in 6/60 (10%) contralateral tumors, but in 0/50 (0%) first malignancies (P = 0.021) and only in 1/22 (5%) synchronous biBC (P = 0.434). None of 52 unilateral breast cancers showed MSI-H status. Shifts of mononucleotide markers were revealed in four second carcinomas from biBC patients but in none of the breast tumors from other categories.

Conclusions

MSI-H is detected with a noticeable frequency in bilateral but not in unilateral breast cancers. Preferable occurrence of MSI-H in second metachronous tumors from biBC patients allows to hypothesize that the development of some contralateral breast neoplasms is casually related to the adjuvant treatment of the initial malignancy.

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Abbreviations

BC:

Breast cancer

biBC:

Bilateral breast cancer

HNPCC:

Hereditary non-polyposis colorectal cancer

NCI:

National Cancer Institute

MMR:

Mismatch repair

MSI:

Microsatellite instability

MSI-H:

High-frequency microsatellite instability

MSI-L:

Low-frequency microsatellite instability

MSS:

Microsatellite stability

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Acknowledgments

This study was supported by INTAS (grant 03-51-4234), RFBR (grants 03-04-49109 and 05-04-49774), and Government of Moscow (grant 05-15).

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Correspondence to Evgeny N. Imyanitov.

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Kuligina, E.S., Grigoriev, M.Y., Suspitsin, E.N. et al. Microsatellite instability analysis of bilateral breast tumors suggests treatment-related origin of some contralateral malignancies. J Cancer Res Clin Oncol 133, 57–64 (2007). https://doi.org/10.1007/s00432-006-0146-0

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  • DOI: https://doi.org/10.1007/s00432-006-0146-0

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