Genetic pathways in the evolution of breast ductal carcinoma in situ

The patterns of allelic loss in 28 cases of pure ductal carcinoma in situ (DCIS) and 25 cases of DCIS associated with invasive ductal carcinoma (IDC) were compared, in order to define whether pure DCIS represented an earlier stage than DCIS associated with IDC in the progression of breast carcinoma. To this aim, the polymerase chain reaction (PCR) was performed on microdissected normal and neoplastic breast tissue, formalin-fixed and paraffin-embedded. Fifteen microsatellite markers were examined, on chromosomes 1p, 3p, 7q, 11q, 12p, 13q, 16q and 17q, mostly focused on regions altered in breast cancer. Loss of heterozygosity (LOH) was greater in pure DCIS than in the DCIS component associated with IDC for 11 out of 15 markers. The difference was statistically significant for D13S260 and D17S800 (p=0.008 and p=0.01, respectively). DCIS associated with IDC showed a lesser degree of alteration than the synchronous IDC component for ten out of 15 markers. In contrast, LOH at D11S1816 and D16S318 was lower in pure DCIS than in DCIS associated with IDC and even greater in the IDC component. These results confirm that DCIS is a possible but not an obligate precursor of invasive breast cancer and suggest that pure DCIS and DCIS associated with IDC may be genetically distinct. The evolution from DCIS to IDC may follow multiple pathways and not a linear model.