A novel diagnostic method targeting genomic instability in intracystic tumors of the breast

Background Even after needle biopsy, the preoperative differential diagnoses of intracystic tumors of the breast are challenging because of their nonspecific radiological characteristics and subtle cytological and histological appearance. The aim of this study is to investigate a novel diagnostic method, targeting genomic instability (GIN) in intracystic tumors of the breast, using tumor DNA from samples obtained by fine-needle aspiration biopsy (FNAB). Methods Thirteen consecutive intracystic tumors of the breast, including five cancers and eight benign tumors, were studied. Three FNAB passages per tumor were used for array comparative genomic hybridization (aCGH) analysis to quantify GIN in each tumor. Tumor DNA from the main tumor, taken from formalin-fixed, paraffin-embedded (FFPE) blocks corresponding to FNAB samples, was also analyzed to compare cytogenetic profiles between these sample types. Results After three FNAB passages, an average of 7.09 μg (0.24–25.0 μg) of DNA was obtained. The quality of the DNA and the aCGH data was excellent, as judged by the mean derivative log ratio spread (DLRSpread) of 0.22 (0.15–0.29). The cytogenetic profiles of paired FNAB and main tumor FFPE samples were highly similar, with an average concordance rate of 97.7 % (81.2–100 %). aCGH analysis from FNAB samples showed significantly more GIN in cancers than in benign tumors, with mean frequencies of aberrant chromosomal regions of 17.5 and 0.34 %, respectively (Wilcoxon’s rank sum test, P = 0.0016). Conclusions Our novel diagnostic method, which targets GIN, can clearly distinguish cancers from benign tumors of breast intracystic lesions with minimal invasion, thereby avoiding the need for surgical excisional biopsy.