Using the DNA Integrity Number to Analyze DNA Quality in Specimens Collected from Liquid-Based Cytology after Fine-Needle Aspiration of Breast Tumors and Lesions.

INTRODUCTION: Cancer genome analysis using next-generation sequencing requires adequate and high-quality DNA samples. Genomic analyses were conventionally performed using formalin-fixed paraffin-embedded sections rather than cytology samples such as cell block or smear specimens. Specimens collected from liquid-based cytology (LBC) have the potential to be sources of high-quality DNA suitable for genetic analysis even after long-term storage. METHODS: We collected breast tumor/lesion fractions from 92 residual LBC specimens using fine-needle aspiration (FNA) biopsy, including breast carcinoma (1 invasive carcinoma and 4 ductal carcinomas in situ), papillomatous lesion (5 intraductal papillomas), and fibroepithelial lesion (19 phyllodes tumors and 53 fibroadenomas) samples, and others (1 ductal adenoma, 1 hamartoma, 1 fibrocystic disease, and 7 unknown). DNA was extracted from all samples and subjected to DNA integrity number (DIN) score analysis. RESULTS: Average DIN score collected from 92 LBC specimens was significantly higher score. In addition, high-quality DNA with high DIN values (7.39 ± 0.80) was successfully extracted more than 12 months after storage of residual LBC specimens. CONCLUSION: Residual LBC specimens collected from FNA of the breast were verified to carry high-quality DNA and could serve as an alternate source for genetic analysis.

Effectiveness of computer-aided diagnosis (CADx) of breast pathology using immunohistochemistry results of core needle biopsy samples for synaptophysin, oestrogen receptor and CK14/p63 for classification of epithelial proliferative lesions of the breast.

AIMS: The aim of this study was to develop a computer-aided diagnosis (CADx) system for identifying breast pathology. METHODS: Two sets of 100 consecutive core needle biopsy (CNB) specimens were collected for test and validation studies. All 200 CNB specimens were stained with antibodies targeting oestrogen receptor (ER), synaptophysin and CK14/p63. All stained slides were scanned in a whole-slide imaging system and photographed. The photographs were analysed using software to identify the proportions of tumour cells that were positive and negative for each marker. In the test study, the cut-off values for synaptophysin (negative and positive) and CK14/p63 (negative and positive) were decided using receiver operating characteristic (ROC) analysis. For ER analysis, samples were divided into groups with <10% positive or >10% positive cells and decided using receiver operating characteristic (ROC) analysis. Finally, these two groups categorised as ER-low, ER-intermediate (non-low and non-high) and ER-high groups. In the validation study, the second set of immunohistochemical slides were analysed using these cut-off values. RESULTS: The cut-off values for synaptophysin, <10% ER positive, >10% ER positive and CK14/p63 were 0.14%, 2.17%, 77.93% and 18.66%, respectively. The positive predictive value for malignancy (PPV) was 100% for synaptophysin-positive/ER-high/(CK14/p63)-any or synaptophysin-positive/ER-low/(CK14/p63)-any. The PPV was 25% for synaptophysin-positive/ER-intermediate/(CK14/p63)-positive. For synaptophysin-negative/(CK14/p63)-negative, the PPVs for ER-low, ER-intermediate and ER-high were 100%, 80.0% and 95.8%, respectively. The PPV was 4.5% for synaptophysin-negative/ER-intermediate/(CK14/p63)-positive. CONCLUSION: The CADx system was able to analyse sufficient data for all types of epithelial proliferative lesions of the breast including invasive breast cancer. This system may be useful for pathological diagnosis of breast CNB in routine investigations.

Positive predictive value for malignancy of pure flat epithelial atypia diagnosis by percutaneous needle biopsy of the breast: management of FEA in ultrasonography.

BACKGROUND: Some reports suggest that the rate of definitive diagnosis of malignant tumors, namely, the final diagnosis being revised to a higher stage, in patients diagnosed as having flat epithelial atypia (FEA) by percutaneous needle biopsy of the breast (PNB) is as low as 0-3 %. However, other reports suggest that the rate is as high as 10 % or more, bringing confusion on this issue. We examined the positive predictive value for malignancy in the patients diagnosed as having pure FEA and the patients' radiolopathological characteristics observed in our hospital. METHODS: Of the patients who underwent PNB in our facility, those who were diagnosed as having pure FEA were recruited as the subjects of this study. RESULTS: Of the 4,197 consecutive patients who underwent PNB, 44 (1.0 %) were diagnosed as having pure FEA following a re-examination. Among 44 cases, 39 cases were selected as the subjects of this study. Among the 39 patients, six patients were diagnosed as having malignant lesions, two of whom had invasive carcinoma of no special type (papillotubular type), one had tubular carcinoma, one had ductal carcinoma in situ (DCIS) of high nuclear grade, one had DCIS of intermediate nuclear grade, and one had DCIS of low nuclear grade. The diameters of 6 malignant lesions were 10-30 mm at ultrasonography (US) examination. Five of the 39 patients had contralateral breast cancer. CONCLUSION: The positive predictive value for malignancy of pure FEA was 15.7 %. The patients with pure FEA may make a follow up without an excisional biopsy when the lesion sizes less than 10 mm on US examination.