BACKGROUND: To determine the benefit of contrast-enhanced ultrasound (CEUS) in the assessment of breast lesions. METHODS: A standardized contrast-enhanced ultrasound was performed in 230 breast lesions classified as BI-RADS category 3 to 5. All lesions were subjected to qualitative and quantitative analysis. MVI (MicroVascular Imaging) technique was used to derive qualitative analysis parameters; blood perfusion of the lesions was assessed (perfusion homogeneity, type of vascularization, enhancement degree). Quantitative analysis was conducted to estimate perfusion changes in the lesions within drawn regions of interest (ROI); parameters TTP (time to peak), PI (peak intensity), WIS (wash in slope), AUC (area under curve) were obtained from time intensity (TI) curves. Acquired data were statistically analyzed to assess the ability of each parameter to differentiate between malignant and benign lesions. The combination of parameters was also evaluated for the possibility of increasing the overall diagnostic accuracy. Biological nature of the lesions was verified by a pathologist. Benign lesions without histopathological verification (BI-RADS 3) were followed up for at least 24 months. RESULTS: Out of 230 lesions, 146 (64%) were benign, 67 (29%) were malignant, 17 (7%) lesions were eliminated. Malignant tumors showed statistically significantly lower TTP parameters (sensitivity 77.6%, specificity 52.7%) and higher WIS values (sensitivity 74.6%, specificity 66.4%) than benign tumors. Enhancement degree also proved to be statistically well discriminating as 55.2% of malignant lesions had a rich vascularity (sensitivity 89.6% and specificity 48.6%). The combination of quantitative analysis parameters (TTP, WIS) with enhancement degree did not result in higher accuracy in distinguishing between malignant and benign breast lesions. CONCLUSIONS: We have demonstrated that contrast-enhanced breast ultrasound has the potential to distinguish between malignant and benign lesions. In particular, this method could help to differentiate lesions BI-RADS category 3 and 4 and thus reduce the number of core-cut biopsies performed in benign lesions. Qualitative analysis, despite its subjective element, appeared to be more beneficial. A combination of quantitative and qualitative analysis did not increase the predictive capability of CEUS.

• Keywords
• Breast cancer, CEUS, Contrast ultrasonography, TI curve, Ultrasound,
• MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Contrast Media MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Breast Neoplasms diagnostic imaging   pathology   MeSH
• Prospective Studies MeSH
• Breast diagnostic imaging   pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Sensitivity and Specificity MeSH
• Neoplasm Grading MeSH
• Ultrasonography, Mammary methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Contrast Media MeSH

The TP63 gene encodes two major protein variants that differ in their N-terminal sequences and have opposing effects. In breast, ΔNp63 is expressed by immature stem/progenitor cells and mature myoepithelial/basal cells and is a characteristic feature of basal-like triple-negative breast cancers (TNBCs). The expression and potential role of TAp63 in the mammary gland and breast cancers is less clear, partly due to the lack of studies that employ p63 isoform-specific antibodies. We used immunohistochemistry with ΔNp63-specific or TAp63-specific monoclonal antibodies to investigate p63 isoforms in 236 TNBCs. TAp63, but not ΔNp63, was seen in tumour-associated lymphocytes and other stromal cells. Tumour cells showed nuclear staining for ΔNp63 in 17% of TNBCs compared to 7.3% that were positive for TAp63. Whilst most TAp63+ tumours also contained ΔNp63+ cells, the levels of the two isoforms were independent of each other. ΔNp63 associated with metaplastic and medullary cancers, and with a basal phenotype, whereas TAp63 associated with androgen receptor, BRCA1/2 wild-type status and PTEN positivity. Despite the proposed effects of p63 on proliferation, Ki67 did not correlate with either p63 isoform, nor did they associate with p53 mutation status. ΔNp63 showed no association with patient outcomes, whereas TAp63+ patients showed fewer recurrences and improved overall survival. These findings indicate that both major p63 protein isoforms are expressed in TNBCs with different tumour characteristics, indicating distinct functional activities of p63 variants in breast cancer. Analysis of individual p63 isoforms provides additional information into TNBC biology, with TAp63 expression indicating improved prognosis.

• Keywords
• Androgen receptor, BRCA1, BRCA2, PTEN, TAp63, Triple-negative breast cancer, ΔNp63,
• MeSH
• Phenotype MeSH
• PTEN Phosphohydrolase genetics   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local genetics   MeSH
• Mutation genetics   MeSH
• Tumor Suppressor Proteins genetics   MeSH
• Protein Isoforms genetics   MeSH
• BRCA1 Protein genetics   MeSH
• BRCA2 Protein genetics   MeSH
• Gene Expression Regulation, Neoplastic genetics   MeSH
• Transcription Factors genetics   MeSH
• Triple Negative Breast Neoplasms genetics   metabolism   mortality   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• BRCA1 protein, human MeSH Browser
• BRCA2 protein, human MeSH Browser
• PTEN Phosphohydrolase MeSH
• Tumor Suppressor Proteins MeSH
• Protein Isoforms MeSH
• BRCA1 Protein MeSH
• BRCA2 Protein MeSH
• PTEN protein, human MeSH Browser
• TP63 protein, human MeSH Browser
• Transcription Factors MeSH