The Role of Allelic Imbalance at Chromosome 2p16 in Breast Cancer Progression

The role of the mismatch repair gene (MSH2) in breast cancer development was investigated using 9 mi- crosatellite polymorphic markers located at the area of the MSH2 gene on chromosome 2p16. The study included 33 samples of invasive breast carcinoma (IBC), 15 samples of carcinoma in situ (CIS) and 19 samples of epithelial hy- perplasia (EH) obtained from 56 patients. There were 11 cases in which more than one pathologic type was ob- tained from the same patient. Loss of heterozygosity (LOH) was detected in 44.6% of the cases. The highest frequency of LOH was reported in IBC (74.4%) compared to 16.3% in CIS and 9.3% in EH. Microsatellite instability (MSI) was reported in 62.5% of the studied patients, 20.45% in EH, 28.8% in CIS and 51.5% in IBC. There was a highly statistically significant difference in the fre- quency of MSI and LOH between the three studied groups (p = 0.001). Our allelotyping analysis of the 11 cases in which there were more than one lesional type in the same patient revealed that, in 7 cases, aberrations were almost similar in different pathologic lesions obtained from the same patient. In 2 of them MSI in certain markers changed into LOH with disease progression providing evidence for the role of genetic aberrations of MSH2 in the transition of hyperplastic mammary epithelium into neoplastic one. In conclusion, the present study represents the first report that demonstrates the implication of MSH2 gene in the de- velopment of sporadic breast carcinoma and its probable precursors. We assume that defects involving the MSH2 gene could promote breast cancer progression through well-defined stages of EH and CIS.