Microsatellite alterations on human chromosome 11 in in situ and invasive breast cancer: A microdissection microsatellite analysis and correlation with p53, ER (estrogen receptor), and PR (progesterone receptor) protein immunoreactivity

Background and Objectives: Microsatellite instability (MSI) has been docume nted in a subset of sporadic tumors. Loss of heterozygosity (LOH) on chromo some 11 loci in breast cancer is a frequent event. The purpose of the prese nt study is to examine the incidence of microsatellite alterations in in si tu and invasive human breast carcinoma and to clarify their significance in regulating the dynamics of cancer progression. Methods: Four highly polymorphic (CA)n repeat microsatellites were used to determine microsatellite alterations in ten ductal carcinoma in situ (DCIS) and 19 invasive ductal carcinoma (IDC). To investigate the expression of p 53, ER (estrogen receptor), and PR (progesterone receptor) association with MSI, immunohistochemistry staining was applied. Results: MSI were detected in 20% (2/10) of DCIS and in 47.4% (9/19) of IDC . The frequency of MSI in IDC was significantly higher than that in DCIS (P <0.001). Also,the MSI seemed to correlate with clinical stage (P = 0.0001) and tumor size (P = 0.004) but not histological grade or age. In addition, we found that 27% of the tumors showed LON at 11q23.3-24 region between lo ci D11S934 and D11S912. Seven of nine MSI cases demonstrated low or no expr ession of p53. However, there was significantly reduced expression of PR, b ut not ER in MSI cases. Conclusions: Our results suggest that breast cancer acquires the RER phenot ype (replication-error phenotype) in the relatively late stages, and that t he RER phenotype is associated with aggressiveness of IDC (infiltrative duc t carcinoma). The result also implicated that mismatch repair failure can a lter the expression of PR but not ER and p53. J. Surg. Oncol. 2000;74:100-1 07. (C) 2000 Wiley-Liss, Inc.