The Diagnostic Value of microRNA Expression Analysis in Detecting Intraductal Papillomas in Patients with Pathological Nipple Discharge.

Patients with pathological nipple discharge (PND) often undergo local surgical procedures because standard radiologic imaging fails to identify the underlying cause. MicroRNA (MiRNA) expression analysis of nipple fluid holds potential for distinguishing between breast diseases. This study aimed to compare miRNA expression levels between nipple fluids from patients with PND to identify possible relevant miRNAs that could differentiate between intraductal papillomas and no abnormalities in the breast tissue. Nipple fluid samples from patients with PND without radiological and pathological suspicion for malignancy who underwent a ductoscopy procedure were analyzed. We used univariate and multivariate regression analyses to identify nipple fluid miRNAs differing between pathologically confirmed papillomas and breast tissue without abnormalities. A total of 27 nipple fluid samples from patients with PND were included for miRNA expression analysis. Out of the 22 miRNAs examined, only miR-145-5p was significantly differentially expressed (upregulated) in nipple fluid from patients with an intraductal papilloma compared to patients showing no breast abnormalities (OR 4.76, p = 0.046), with a diagnostic accuracy of 92%. miR-145-5p expression in nipple fluid differs for intraductal papillomas and breast tissue without abnormalities and, therefore, has potential as a diagnostic marker to signal presence of papillomas in PND patients. However, further refinement and validation in clinical trials are necessary to establish its clinical applicability.

Breast cancer nipple discharge exosomal microRNAs are stable under degradative conditions.

We have previously shown that microRNAs (miRNAs) in nipple discharge are potential diagnostic biomarkers. In particular, exosomes are present in nipple discharge. Herein, we sought to elucidate the protective role of exosomes on miRNAs in nipple discharge and investigate the stability of miRNAs encapsulated in exosomes under degradative conditions. A novel TTMAAlPc-RNA complex method was used to measure the RNase concentration in colostrum and nipple discharge. Quantitative real-time polymerase chain reaction was performed to test the stability of exogenous synthetic miRNAs (cel-lin-4-5p and cel-miR-2-3p) and endogenous miRNAs (hsa-miR-4732-5p, hsa-miR-3646, hsa-miR-4484, and kshv-miR-K12-5-5p). RNase was present and functional in colostrum and nipple discharge. Endogenous miRNAs were more stably expressed compared to exogenous miRNAs at room temperature and 4°C. Triton X-100 (1%, 30 min) destroyed the exosomal membrane, causing RNA degradation in colostrum but not in nipple discharge. Therefore, we confirmed that exosomes in colostrum and nipple discharge could protect miRNAs from degradation by RNase. Exosomes in nipple discharge may be more resistant to Triton X-100 lysis compared to those in the colostrum. Exosomal miRNAs in nipple discharge in breast cancer are stable under degradative conditions. Differential Triton X-100 sensitivity of exosomes of nipple discharge and colostrum warrants further investigation.

Evaluation and management of pathological nipple discharges without using intraductal imaging methods.

BACKGROUND: The most common cause of pathological nipple discharge (PND) is single papilloma, which is a benign intraductal lesion (BIL). However, underlying malign (MIL) or high-risk intraductal lesions (HIL) should be considered during examination. AIM: To reveal the value of conventional imaging methods (CIM), discharge characteristics, and cytology in lack of intraductal imaging methods to detect intraductal lesions (IL) and MIL that cause PND. METHODS: We compared the pathological findings with the characteristics of discharge, CIM, and cytology findings of the patients who admitted to our clinic with nipple discharge and underwent duct excision (n = 111). RESULTS: IL were detected in 69 (62.2%) patients as BIL (n = 31), HIL (n = 23), and MIL (n = 15). Most of the IL was observed with bloody, serosanguineous, and serous discharges (83.3%, 76.2%, and 69.2%, respectively). The sensitivities of ultrasonography, MRI, and cytology in detecting IL were found to be 50.7%, 42.6%, and 74.1%, while their specificities were found to be 73.8%, 88.2%, and 48.6%, respectively. None of the CIM was sufficient to detect MIL in 5 (33.3%) patients. The appearance of red blood cells detailed in cytology was significantly related to IL (p < 0.01), whereas the presence of inflammatory cells was related to ductal ectasia and periductal mastitis (p < 0.001). CONCLUSIONS: Although patients' physical examinations, CIM, and cytology findings were normal, duct excision procedures should be applied to exclude MIL or HIL, which can be a cause of discharge in case of suspicious color. The details in cytology reports have a role in increasing the value of cytology.

[Circulating microRNAs in the Identification of Biological Fluids: A New Approach to Standardization of Expression-Based Diagnostics].

Molecular profiling of normal tissues is a regular and necessary step when developing systems for expression analyses in biological samples, including diagnostic panels for various diseases and conditions. Yet there are still no rigorous criteria to allow precise typing of normal tissues. A main problem is that the methods employed in diagnostic expression testing are difficult to standardize. While various technologies, instruments, and reagents are available, universal protocols of handling biological material are lacking, thus impairing the reproducibility of data from independent studies. The review describes a new approach to standardizing circulating microRNA studies in forensic biology, which has relatively recently (7-8 years ago) come to employ RNA markers in molecular typing of tissues and biological fluids. Forensic biology is now one of the few disciplines where several panels of tissue mRNA markers have been developed within a short period of time and a number of specific microRNA markers have been established and validated for several biological fluids. To allow their successful use, new protocols have been combined with the available, rigidly standardized system of genetic personal identification. Although a ready diagnostic product has still not been obtained with this well-working approach, the apparent efficiency of the standardization methods clearly demonstrates that the problem is possible to solve in other biomedical fields, including those where RNA-based diagnostic protocols are still under development.

Diagnosis of Nipple Discharge: Value of Magnetic Resonance Imaging and Ultrasonography in Comparison with Ductoscopy.

BACKGROUND: Pathologic nipple discharge, which is a common reason for referral to the breast imaging service, refers to spontaneous or bloody nipple discharge that arises from a single duct. The most common cause of nipple discharge is benign breast lesions, such as solitary intraductal papilloma and papillomatosis. Nevertheless, in rare cases, a malignant cause of nipple discharge can be found. AIMS: To study the diagnostic value of ultrasonography, magnetic resonance imaging, and ductoscopy in patients with pathologic nipple discharge, compare their efficacy, and investigate the importance of magnetic resonance imaging in the diagnosis of intraductal pathologies. STUDY DESIGN: Diagnostic accuracy study. METHODS: Fifty patients with pathologic nipple discharge were evaluated by ultrasonography and magnetic resonance imaging. Of these, 44 ductoscopic investigations were made. The patients were classified according to magnetic resonance imaging, ultrasonography, and ductoscopy findings. A total of 25 patients, whose findings were reported as intraductal masses, underwent surgery oincluding endoscopic excision for two endoscopic excision. Findings were compared with the pathology results that were accepted as the gold standard in the description of the aetiology of nipple discharge. In addition, magnetic resonance imaging, ultrasonography and ductoscopy findings were analysed comparatively in patients who had no surgery. RESULTS: Intraductal masses were reported in 26 patients, 20 of whom operated and established accurate diagnosis of 18 patients on magnetic resonance imaging. According to the ultrasonography, intraductal masses were identified in 22 patients, 17 of whom underwent surgery. Ultrasonography established accurate diagnoses in 15 patients. Intraductal mass was identified in 22 patients and ductoscopy established accurate diagnoses based on histopathologic results in 16 patients. The sensitivities of methods were 75% in ultrasonography, 90% in magnetic resonance imaging, and 94.6% in ductoscopy. The specificities were 66.7% in ultrasonography, 66.7% in magnetic resonance imaging, and 40% in ductoscopy. Intraductal papillomas were mostly observed as oval nodules with well-circumscribed smooth margins within dilated ducts and persistant in the dynamic analysis. Lesions that protruded into the lumen of the ducts, either solitary or multiple, were characteristic ductoscopy findings of our patients who were diagnosed as having papilloma/papillomatosis. CONCLUSION: Magnetic resonance imaging and ductoscopy had no statistical superiority over each other, however they were superior to ultrasonography in the diagnosis of pathologic nipple discharge. Magnetic resonance imaging may be highly sensitive for diagnosing nipple discharge with new techniques and sequences and a non-invasive method that more advantageous for showing ductal tree visualization and is able to detect completely obstructed intraductal lesions.

Different Levels of CEA, CA153 and CA125 in Milk and Benign and Malignant Nipple Discharge.

BACKGROUND: The aim of this study was to assess the diagnostic values of three breast tumor markers (i.e., CEA, CA153 and CA125) in milk and nipple discharge in the prediction of different breast diseases diagnoses. METHODS: Three hundred thirty-six patients (96 breast cancer and 240 benign disease patients) with nipple discharge and a control group of 56 healthy parturient participants were enrolled in the present study. Nipple discharge samples were preoperatively collected from the patients, and milk was collected from the colostrum of the parturient participants. The samples were assayed for the CEA, CA153 and CA125 levels. Cutoff values were determined for the detection of breast diseases using ROC curves. RESULTS: The levels of CEA, CA153 and CA125 were significantly different between the nipple discharge and the milk (all ps < 0.001). In the nipple discharge, the CEA and CA153 levels in the breast cancer group were significantly greater than those in the benign group (all ps < 0.001), and cutoff values of 263.3 ng/mL and 1235.3 U/mL, respectively, were established. However, the expression of CA125 did not differ significantly between the breast cancer and benign groups. CONCLUSION: Differences in the apparent expression levels of CEA, CA153 and CA125 in patients with nipple discharge and healthy persons were validated. The present data suggest that CEA and CA153 might potentially be useful in the differential diagnoses of benign tumors and breast cancer. CA125 did not seem to be useful for breast cancer detection.

[Bloody nipple discharge in an 3,5-month-old boy]. / Wyciek krwistej wydzieliny z gruczolów sutkowych u 3,5-miesiecznego chlopca.

Bloody nipple discharge in an infant is a distressing finding both for parents and the pediatrician who consults the baby. In adults the bleeding can be associated with breast carcinoma, especially when it is unilateral. In infants breast carcinoma are extremely rare. Usually, the bleeding is a benign process, but that does not mean that the children with this symptom should not be diagnosed and controlled. This paper reports a 3,5-month-old boy with bilateral bloody nipple discharge. Additionally, it presents previously described cases of bleeding from the nipples in children and proposed diagnostic approach.