Low frequency of microsatellite instability in sporadic breast cancer.
In some tumors, defects in mismatch repair enzymes lead to errors in the replication of simple nucleotide repeat segments. This condition is commonly known as microsatellite instability (MSI) because of the frequent mutations of microsatellite sequences. Although the MSI phenotype is well recognized in some colon, gastric, pancreatic, and endometrial cancers, reports of MSI in breast cancer are inconsistent. The purpose of this study was to determine the presence of MSI in breast cancer and to correlate its occurrence with clinicopathological parameters, including expression of estrogen and progesterone receptors. We have analyzed the status of 10 different microsatellite loci (mono and dinucleotide repeats). Mmicrosatellite size patterns and LOH were compared in 88 paired breast-cancer/peripheral-blood DNA samples. Fluorescent polymerase chain reaction (PCR) for typing microsatellites coupled with DNA fragment analysis in an automated DNA sequencer was applied. Microsatellite instability in at least two microsatellite markers was observed in 6 out of 88 (7%) of the cases, all beloging to stage II or III. LOH was found in 48/88 (55%) of the cases. Five of the six cases with MSI also had LOH in other markers different from those of MSI. These MI and LOH data were analysed using a range of clinicopathological parameters, no correlation between MSI and histopathological characteristics were found. A significant correlation was observed between MSI and negative expression of both estrogen and progesterone receptors (p<0.02), indicating a possible relatioship between specific genetic changes at these microsatellite regions and hormonal deregulation in the progresion of breast cancer.
Caldes
T
T
Department of Immunology, San Carlos University Hospital, 28040-Madrid, Spain.
Perez-Segura
P
P
Tosar
A
A
De La Hoya
M
M
Diaz-Rubio
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone