Micro Rna-21 Expression Levels in Invasive Breast Carcinoma with a Non-Invasive Component

Invasive ductal carcinomas with a non-invasive component (IDC-DCIS) are classified as a group of invasive breast carcinomas, together with pure invasive ductal carcinomas of the breast (IDC). MicroRNA-21 (miR-21) has been characterized as a factor of breast cancer invasiveness, however the difference in miR-21 expression levels between IDC-DCIS and pure IDC tumors and the correlations with standard diagnostic and prognostic parameters inside the IDC-DCIS group are unknown. Our aim was to determine if miR-21 had the ability to distinguish these two invasive breast cancer groups. Levels of miR-21 expression were measured by a stem-loop quantitative Real-Time PCR (RT-qPCR) method. Expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and proliferative index Ki-67 were evaluated by immunohistochemistry. IDC-DCIS tumors had significantly lower levels of miR-21 expression in grade 2 (P=0.003, Mann-Whitney U test), ER positive (P=0.025, Mann-Whitney U test) and PR positive tumors (P=0.024, Mann-Whitney U test) than pure IDCs. miR-21 levels showed a different pattern of expression in IDC-DCIS compared to IDC tumors, which is based on the difference in miR-21 expression between Her-2 negative and Her-2 positive IDC-DCIS tumors (P=0.030, Mann-Whitney U test) and high negative correlation of miR-21 levels with PR levels (rho=-0.886, P=0.006, Spearman correlation). According to our results, IDC-DCIS breast carcinomas act in a different manner in pure IDC tumors with regard to the relations between miR-21 expression levels and the standard diagnostic and prognostic parameters, such as Her-2 status, ER and PR status and protein levels

Discrimination between normal and malignant breast tissues by synchronous luminescence spectroscopy

Studies of fluorescence from endogenous molecules in tissues are common for applications such as detection or characterization of early disease. Breast cancer is one of the most common malignant tumor among women and good screening methods are therefore of considerable interest. We have applied synchronous luminescence spectroscopy (SLS) to examine specimens of excised breast tissues. Measurements have been made in the 330 nm to 650 nm range of excitation wavelengths and constant wavelength interval varying from 30 nm to 120 nm on 21 normal and 21 malignant breast tissue samples. Significant differences between SLS patterns of normal and malignant tissues are detected and related to the discrepancy in concentrations of extracellular proteins and co-enzymes. Malignant tissue identification criteria are established on the basis of spectral peak areas of SLS spectra that correspond to constant wavelength intervals where the most pronounced differences are observed. These characteristic intervals are chosen from the difference of averaged three-dimensional SLS patterns of normal and malignant breast tissues. Using observed statistically significant spectral differences as classification criteria we tested classification success rate of presented SLS method

miR-155 expression level changes might be associated with initial phases of breast cancer pathogenesis and lymph-node metastasis

BACKGROUND: Breast carcinoma is heterogeneous disease. Understanding the process of invasion and metastasis and the selection of the therapy for patients with breast carcinomas still remains difficult. MicroRNAs are powerful gene expression regulators. Because of inconsistent findings, we have analyzed potential difference in miR-155 levels in three breast cancer groups. OBJECTIVES: Our goals were to examine miR-155 expression levels in normal tissue, non-invasive and invasive breast carcinomas, and their association with standard clinical and pathological parameters and oncomiR-21, and to investigate the ability of miR-155 to separate invasive breast carcinomas with non-invasive component from pure invasive. METHODS: In the group of 40 breast tissue samples, relative expression levels of miR-155 were examined with stem-loop quantitative real-time PCR using TaqMan technology. RESULTS: The significant difference among four examined groups of the breast tissue was detected (p = 0.001). In the group of pure invasive tumors, patients with positive nodal status had significantly higher miR-155 levels (p = 0.046). CONCLUSION: Our results suggest that miR-155 might be involved in breast cancer pathogenesis and in tumor spreading to the lymph nodes, and that it might be used as biomarker for additional stratification of patients with invasive breast carcinomas with non-invasive component

The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion

MicroRNA-21 (miR-21) overexpression is characteristic for various types of tumors, but it is still unknown whether its expression levels differ between invasive and non-invasive breast carcinomas. The main goal of the study was to determine the difference in miR-21 expression among normal tissue, non-invasive, invasive with non-invasive component, and pure invasive breast cancer samples, to explain its potential role and significance in breast cancer invasiveness. The second goal was to propose miR-21 as molecular marker of breast cancer invasiveness and potential target for future anti-miR therapies for the prevention of invasion and metastasis. In order to reveal the role of miR-21 in breast cancer invasiveness, we measured miR-21 expression levels in 44 breast cancer and four normal samples by stem-loop real-time RT-PCR using TaqMan technology. Relative expression levels of miR-21 were significantly higher in invasive than in other groups (P = 0.002) and significantly higher in invasive compared with invasive with non-invasive component group in histological (P = 0.043) and nuclear grade 2 (P = 0.036), estrogen-receptor-positive (ER+) (P = 0.006), progesterone-receptor-positive (PR+) (P = 0.008), ER+ PR+ (P = 0.007), and proliferation index (Ki-67) LT = 20 % (P = 0.036) tumors. Our findings suggest that miR-21 could be independent molecular marker of breast cancer invasiveness and potential target for future anti-miR therapies for the prevention of invasion and metastasis

Higher miR-21 expression in invasive breast carcinomas is associated with positive estrogen and progesterone receptor status in patients from Serbia

MicroRNAs play essential role in breast carcinoma progression and invasion. Our principal goals were to assess clinicopathological and prognostic correlations of microRNA-21 (miR-21) expression levels in a group of 39 Serbian breast cancer patients with invasive lobular (ILC), ductal (IDC), or mixed (ILC-IDC) breast carcinomas and in order to discover the role of miR-21 in potential novel form of stratification of the patients with different estrogen receptor (ER) and progesterone receptor (PR) status. MiR-21 expression levels were measured by stem-loop real-time RT-PCR using TaqMan technology. ER, PR, human epidermal growth factor 2 receptor (Her-2), and proliferative index (Ki-67) were evaluated by immunohistochemistry. MiR-21 levels do not vary among ILC, IDC, and ILC-IDC subgroups. MiR-21 expression levels varied significantly in the age, tumor size, Ki-67, and different grade (p = 0.030, p = 0.036, p = 0.027 and p = 0.032, respectively) subgroups. ER? and PR? showed higher miR-21 levels than their negative receptor status paired groups ER-and PR-with p = 0.012 and p = 0.018, respectively. MiR-21 positively correlated with ER and PR status (p = 0.018, rho = 0.379 and p = 0.034, rho = 0.345, respectively). Our findings suggest that miR-21 emulates transitional form of expression and that the levels of expression might be useful for stratification of the patients with different receptor status with the purpose to seek for new therapy approaches especially for the patients with the lack of response to conventional endocrine therapy

TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC

Background: Breast carcinomas (BC) belong to a heterogeneous group of malignant diseases. Correct categorization of BC based on molecular biomarkers has a very important role in deciding the proper course of therapy for each patient. It has been already shown that the decrease of TIMP metalloproteinase inhibitor 3 (TIMP-3) together with overexpression of microRNA-21 (miR-21) might be involved in the process of BC invasion. This is the first study that examined relationship among miR-21, TIMP-3 mRNA and TIPM-3 protein levels in BC groups formed according to invasiveness. Methods: In this study, we used 46 breast cancer samples. Estrogen and progesterone receptor (ER, PR) protein levels were evaluated by immunohistochemistry (IHC) method. TIMP-3 mRNA expression was examined by two-step real-time quantitative PCR (qRT-PCR). Western blot analysis was performed for 16 samples. Results: Statistically significant differences in TIMP-3 expression levels between invasive groups were discovered in ER positive (ER+) (p = 0.015), Her-2 negative (p = 0.026) subgroups, and patients without lymph-node metastasis (p = 0.039). Interestingly, significant positive correlation was detected between miR-21 and TIMP-3 mRNA levels (P LT 0.001, p = 0.949) in the group of in situ tumors. TIMP-3 mRNA expression levels highly negatively correlated with levels of miR-21 in PR + invasive BCs (p = 0.007, p = -0.641). TIMP-3 protein levels negatively correlated with miR-21 levels in pure invasive BCs. Conclusion: These data suggest that signaling pathways involved in formation and progression of BCs in groups formed according to invasiveness might be different. Our findings propose that TIMP-3 mRNA expression levels could be significant prognostic parameter, but within specific BC subtypes

Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels

Breast cancer (BC) is a heterogeneous group of diseases that still represents a major cause of death in the female population. MicroRNAs (miRNAs, miRs), such as miR-221 and miR-222, have been shown to be involved in BC pathology by acting via its target genes such as tissue inhibitor of metalloproteinase 3 (TIMP3). The main goals of this study were to find differences in miR-221/222 levels of expression in BC groups based on invasiveness, and to investigate the association with estrogen receptor (ER), TIMP3 messenger RNA (mRNA) levels, and clinicopathological characteristics of patients and tumors. In this study, we measured levels of miR-221/222 in 63 breast tissue samples by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using TaqMan(A (R)) technology and immunohistochemistry. miR-221/222 levels varied significantly across groups based on invasiveness (P LT 0.001). In in situ tumors, miR-221 and miR-222 were negatively associated with ER (P = 0.001, r = -0.714, and P = 0.013, r = -0.585, respectively). In invasive breast carcinomas associated with non-invasive tumors, miR-222 was inversely associated with ER (P = 0.039, r = -0.620). Pure invasive BCs showed a positive correlation of miR-221 and miR-222 with TIMP3 mRNA levels (P = 0.008, r = 0.508, and P = 0.010, r = 0.497, respectively). An increase in miR-221/222 might be an important event for in situ carcinoma formation, and miR-221/222 may be important molecules that highlight potential differences between invasive breast carcinomas associated with non-invasive and pure invasive BCs