Accumulation of chromosomal imbalances from intraductal proliferative lesions to adjacent in situ and invasive ductal breast cancer

Carcinoma of the breast is thought to evolve through a sequential progressi on from normal to proliferative epithelium and eventually into carcinoma. H ere lumpectomy specimens from five patients were studied, selected for the presence of ductal hyperplasia without atypia, atypical ductal hyperplasia. ductal carcinoma in situ, and invasive ductal carcinoma. Laser microdissec tion of tissue allowed precise sampling and direct correlation of phenotypi c and genotypic changes. Analyses of the samples revealed an increasing mea n number of chromosomal changes occurring with increasing histologic severi ty, and for the first time chromosomal abnormalities were demonstrated in d uctal hyperplasia without atypia. Chromosomal changes found in each of the four histologic entities included gains on 10q, 12q, 16p, and 20q and loss on 13q. In ductal hyperplasia without atypia, gain on 20q as well as loss o n 13q was detected with high frequency (four of five samples). Alterations identified in more than 50% of atypical ductal hyperplasia samples included gains on 3p, 8q, 15q, and 22q and loss on 16q. In ductal carcinoma in situ , gain of DNA on Iq and 17q and loss on 4q were additionally found, and in invasive ductal carcinoma, further gains on 6p, 10q, 11q13, and 17p were id entified. The chromosomal alterations occurring in the different histopatho logic lesions strongly suggest that these regions harbor tumor suppressor g enes or oncogenes significant for the development of ductal carcinoma of th e breast.