Background: Columnar cell lesions (CCL) and atypical ductal hyperplasia (ADH) have been found to frequently coexist and share molecular changes with in situ and invasive breast cancer, suggesting that CCL and ADH may be precursors to invasive disease. These conclusions are, however, largely based on studies examining synchronous CCL and/or ADH from patients diagnosed with more advanced disease. In this study, we assessed allelic imbalance (AI) in pure CCL or ADH specimens to characterize molecular changes associated with the initiation and development of early breast lesions. Methods: DNA samples were obtained from laser microdissected lesions from patients diagnosed with CCL with (n=23) or without (n=18) atypia or with ADH (n=32) without synchronous in situ or invasive disease. All specimens were characterized by a single breast pathologist. A microsatellite marker panel representing 26 chromosomal regions commonly altered in breast cancer was used to assess patterns of AI. Results: The average AI frequency was 9% (range 0-20%) in CCL and 8% (range 0-25%) in ADH with no significant difference in levels of AI between CCL and ADH. The highest frequency of AI occurred at chromosomes 6q22-q23 and 22q13 (20%) in CCL and 8q24 (23%) in ADH. AI occurred at significantly higher levels at chromosome 13q14 (P<0.05) in ADH compared to CCL and at 22q13 (P<0.01) in CCL compared to ADH. Conclusions: Differences in patterns of AI, especially at chromosome 22q13 suggest that CCL may not be a precursor to ADH and that the two diseases evolve along independent pathways. Low overall levels of AI in pure CCL and ADH suggest that the majority of these lesions are not genetically advanced. The variability in levels of AI in both CCL and ADH lesions may contribute to clinical heterogeneity in behavior and aggressiveness and suggests a need to assess molecular characteristics of early lesions to better predict outcomes.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5056.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO