Abstract P4-04-14: A novel diagnostic method targeting genomic instability in breast intracystic tumors
Authors: H Yano, M Oikawa, M Matsumoto, R Otsubo, K Shibata, T Hayashi, K Abe, N Kinoshita, T Nagayasu
Journal: Cancer Research (2013)

Abstract Background: In breast lesions, indication for surgery is usually determined by pathological diagnosis together with radiological findings. However, differential preoperative diagnoses of intracystic papillary carcinomas vs. papillomas are very challenging even after needle biopsy, because of their non-specific radiological characteristics, and modest cytological and histological appearance. Hence, surgical excisional biopsy is recommended in the clinical management of these lesions, especially when associated with risk factors for malignancy, such as age (≥50years) and the presence of microcalcifications. Meanwhile, genomic instability (GIN) is an important hallmark of cancer, which may be useful for distinguishing cancers from benign tumors. Specifically, intracystic papillary carcinoma harbors significant GIN compared with intracystic papilloma.We have recently reported that genome-wide copy number aberrations can easily be detected by array comparative genomic hybridization (aCGH), which can then be used to quantify GIN. The aim of this study is to investigate a novel diagnostic method, targeting GIN in breast intracystic tumors, using tumor DNA from samples obtained by fine-needle aspiration biopsy (FNAB). Material and Methods: Thirteen consecutive breast intracystic tumors resected at Nagasaki University Hospital between August 2010 and March 2012, which included five cancers (four invasive carcinomas and one non-invasive carcinoma) and eight benign tumors (five papilloma, two ductal adenoma and one sclerosing papilloma), were studied. FNABs were performed by an experienced surgeon using a 22-gauge aspiration needle, who performed three FNAB passages per tumor. Tumor DNA was extracted using the QIAmp DNA Mini Kit (Qiagen), followed by aCGH analysis using a high-density oligonucleotide microarray (Agilent® SurePrint G3 8×60k microarray). The frequency of aberrant chromosomal regions in the total genome was used as an indicator of GIN. Tumor DNA from the main tumor, taken from FFPE blocks corresponding to FNAB samples, was also analyzed to assess the similarity of cytogenetic profiles. Results: After three FNAB passages, sufficient amounts of DNA were obtained with an average of 7.09 μg (0.24-16.1 μg). 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), which estimates the log ratio noise by calculating the spread of log ratio differences between consecutive probes along all chromosomes. Further, the cytogenetic profile of paired FNAB and main tumor FFPE samples were highly similar, with an average concordance rate, defined as the ratio of the length of same copy number within pairs, of 97.7% (81.2-100%). aCGH analysis from FNAB samples showed that cancers harbored significantly more GIN than 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 genomic instability, can clearly distinguish cancers from benign tumors of breast intracystic lesions with minimum invasion, thereby avoiding the need for surgical excisional biopsy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-04-14.