Evidence of chromosomal alterations in pure usual ductal hyperplasia as a breast carcinoma precursor

Abstract

Previous studies have shown the chromosomal alterations in usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) in the breast with bilateral ductal hyperplasia or adjacent to invasive ductal carcinoma (IDC). However, the role of UDH as a putative precursor of breast IDC is not clear and has not been fully addressed. The aim of this study was to clarify the role of UDH in breast carcinoma pathogenesis. To investigate chromosomal imbalances and commonality, samples of pure unilateral UDH (n=20) were obtained by laser capture microdissection and analyzed by comparative genomic hybridization. Other ductal lesions, including ADH (n=2), high-grade DCIS (n=3), and grade III IDC (n=5), were assessed at the same time for comparison. The mean values of alteration were 1.95 (39/20) in UDH, 9.5 (19/2) in ADH, 11.0 (33/3) in DCIS and 18.2 (89/5) in IDC, respectively. Some common predisposition regions for the deletions were at chromosomes 1p36-pter, 13q11-14, and 16q11-23, while the high frequency amplification regions were 1q31-qter, 3p21-pter, 6p21-pter, 11q11-14, 12q11-qter, 13q21-qter, 16p12-pter, 17q12-22, and 20q. The genetic abnormalities in the spectrum of breast ductal hyperplasia revealed that the deletion of DNA copy in UDH was the lowest, and gradually increased in the lineages of ADH, DCIS and IDC. Results showed that a significant portion of UDH shares common genetic alterations with ADH, DCIS and IDC, indicating UDH as a precursor of invasive breast ductal carcinoma.