Molecular Biological Differences Between Younger and Older Breast Cancer Patients Based on the Status of a Microsatellite Marker

ABSTRACT

PURPOSE: Younger women exhibit more aggressive pathological features of breast cancer than older women, based on previous studies. We wished to evaluate any molecular biological differences in breast cancer between younger and older women by determining the status of a microsatellite marker. METHODS: Microsatellite instability (MSI) and loss of heterozygosity (LOH) were investigated in paired tumour and normal tissue DNA from 32 younger (age less than 40 years old) and 32 older (age more than 50 years old) breast cancer patients with 12 simple repeated primer sets. RESULTS: MSI was observed at a single locus in 5 (15.6%) of the younger patients. In older patients, MSI was observed at a single locus in 5 (15.6%) and at multiple loci in 1 (3.1%) of the older patients. LOH was noted at a single locus in 7 (21.8%) and at multiple loci in 22 (68.7%) of 32 younger patients. In older patients, LOH was noted at a single locus in 9 (28.1%) and at multiple loci in 15 (46.9%). The greatest frequency of LOH was at loci UT5320 (37.5%), D8S321 (34.4%), D9S242 (31.3%), and D19S394 (31.3%) in younger patients and at loci L17686 (34.4%) and D19S394 (28.1%) in older patients. LOHs at D19S394 and L17686 were highly identified in both age groups. LOHs at D9S242 and D8S321 were significantly higher in the carcinomas of younger women (P=0.013, P=0.016, respectively). The LOH status was unrelated to clinical stage, nodal status, tumour size, histological grade or estrogen receptor (ER) status. A LOH at D8S321 was associated with tumor size (P=0.048) and a LOH at UT5320 was associated with histological grade (P=0.012) and ER status (P=0.018). CONCLUSION: These results indicate that the pattern of chromosomal alterations are not exactly the same, especially at loci D9S242 and D8S321, in the carcinomas of the two age groups and suggest that the molecular pathogenesis of the carcinomas is not similar.