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Management of women with ductal carcinoma in situ (DCIS) is currently a major concern. Biological characteristics in the light of progression from DCIS to invasive ductal carcinoma (IDC) remain unknown. Our previous study [1] investigating synchronous lesions demonstrated higher LOH frequencies in parallel with the tumor progression from atypical ductal hyperplasia (ADH) to DCIS and IDC [1]. We report here an asynchronous LOH analysis of DCIS from patients who subsequently developed IDC.  We collected 88 biopsy specimens, originally diagnosed benign, from the patients who subsequently developed IDC in the ipsilateral breast. Seven asynchronous lesions of initial biopsy (re-evaluation was DCIS) and the respective IDC were subjected to LOH analysis in this study. Thirteen microsatellite markers, which were mapped to and/or very close to the tumor suppressor genes or regions with frequent LOH in breast cancer, were used.  LOHs were observed in parallel with the tumor progression from DCIS to IDC in all cases except for one that developed IDC in another quadrant. The six patients developed IDC near the initial biopsy, and presented similar or identical histopathologic features. LOH analysis of biopsy specimens from patients who subsequently developed IDC demonstrated acquisition of genetic change at an earlier stage, as the same allele at the same genomic locus was lost in DCIS.  Our results suggest that genetic alternations accumulate during cancer progression from DCIS to IDC, and DCIS presents a high risk of developing invasive transformation.

Asynchronous LOH analysis of ductal carcinoma in situ from patients who subsequently developed invasive ductal carcinoma