Microsatellite instability analysis of bilateral breast tumors suggests treatment-related origin of some contralateral malignancies.
OBJECTIVE
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 > or = 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.
Kuligina
Ekatherina Sh
ESh
Laboratory Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, St. Petersburg, 197758, Russia.
Grigoriev
Maxim Yu
MY
Suspitsin
Evgeny N
EN
Buslov
Konstantin G
KG
Zaitseva
Olga A
OA
Yatsuk
Olga S
OS
Lazareva
Yulia R
YR
Togo
Alexandr V
AV
Imyanitov
Evgeny N
EN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D005260:Female; D005819:Genetic Markers; D006801:Humans; D053842:Microsatellite Instability; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects
D005819:Genetic Markers