Microsatellite instability correlates with negative expression of estrogen and progesterone receptors in sporadic breast cancer.
In some tumors, defects in mismatch repair enzymes lead to errors in the replication of simple nucleotide repeat segments RER+ tumors. 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 analyzed the status of 10 different microsatellite loci (mono- and dinucleotide repeats). In this study, microsatellite size patterns 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. MSI in at least two microsatellite markers was observed in 6 out of 88 (7%) of the cases, all belonging to Stage II or III. These MSI data were analyzed 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 relationship between specific genetic changes at these microsatellite regions and hormonal deregulation in the progression of breast cancer.
Caldés
T
T
Laboratory of Molecular Oncology, San Carlos University Hospital, Madrid, Spain. tcaldes@hcsc.insalud.es
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 / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology; D002874:Chromosome Mapping; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D013030:Spain
D005819:Genetic Markers; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone