Expression of metalloproteinases 2 and 9 and plasma zinc concentrations in women with fibroadenoma.

OBJECTIVE: This study aims to investigate the association between the immunohistochemical expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and plasma zinc in women with fibroadenoma. METHODS: This cross-sectional study included 37 premenopausal women with fibroadenoma. Waist circumference and body mass index of the participants were measured. Plasma zinc concentrations were determined using atomic flame absorption spectrophotometry. Fragments of breast tissue were fixed and incubated with primary mouse monoclonal antibodies (monoclonal antibodies matrix metalloproteinase -2 -507 and monoclonal antibodies matrix metalloproteinase -9-439). Semi-quantitative analysis of matrix metalloproteinase-2 and matrix metalloproteinase-9 immunoreactivity was performed. Spearman's test and Friedman's test were used for statistical analyses. The p<0.05 were considered statistically significant. RESULTS: The average age of the participants was 32.81±9.51 years. The body mass index and waist circumference values were within the normal range. The mean plasma zinc concentration was 42.73±13.84 µg/dL, with 94.6% inadequacy. A statistically significant difference was found between the positive expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 (p=0.0184). There was no significant correlation between the matrix metalloproteinase expression and the plasma zinc levels. CONCLUSIONS: Women with fibroadenoma had hypozincemia and positive expression of metalloproteinases.

Influence of CYP19A1 gene expression levels in women with breast cancer: a systematic review of the literature.

Breast cancer is the most frequently diagnosed malignant neoplasm in women and is considered a multifactorial disease of unknown etiology. One of the major risk factors is genetic alteration. Changes in CYP19A1 gene expression levels have been associated with increased risk and increased aggressiveness of breast cancer. Increased CYP19A1 gene expression and/or aromatase activity are among the major regulatory events for intratumoral production of estrogens in breast malignant tissues. This systematic review aimed to investigate the influence of CYP19A1 gene expression levels in women with breast cancer. The research was carried out using the PubMed, Scopus, and Web of Science databases. Searches were conducted between February 2 and May 15, 2019. Inclusion criteria were studies published between 2009 and 2019, English language publications, and human studies addressing the gene expression of CYP19A1 in breast cancer. A total of 6.068 studies were identified through PubMed (n=773), Scopus (n=2,927), and the Web of Science (n=2,368). After selecting and applying the inclusion and exclusion criteria, six articles were included in this systematic review. This systematic review provides evidence that increased or decreased levels of CYP19A1 gene expression may be related to pathological clinical factors of disease, MFS, OS, DFS, WATi, markers of metabolic function, concentrations of E1, FSH, and in the use of multiple exons 1 of the CYP19A1 gene in breast cancer.

Expression of metalloproteinases 2 and 9 and plasma zinc concentrations in women with fibroadenoma

SUMMARY OBJECTIVE: This study aims to investigate the association between the immunohistochemical expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and plasma zinc in women with fibroadenoma. METHODS: This cross-sectional study included 37 premenopausal women with fibroadenoma. Waist circumference and body mass index of the participants were measured. Plasma zinc concentrations were determined using atomic flame absorption spectrophotometry. Fragments of breast tissue were fixed and incubated with primary mouse monoclonal antibodies (monoclonal antibodies matrix metalloproteinase -2 -507 and monoclonal antibodies matrix metalloproteinase -9-439). Semi-quantitative analysis of matrix metalloproteinase-2 and matrix metalloproteinase-9 immunoreactivity was performed. Spearman's test and Friedman's test were used for statistical analyses. The p<0.05 were considered statistically significant. RESULTS: The average age of the participants was 32.81±9.51 years. The body mass index and waist circumference values were within the normal range. The mean plasma zinc concentration was 42.73±13.84 µg/dL, with 94.6% inadequacy. A statistically significant difference was found between the positive expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 (p=0.0184). There was no significant correlation between the matrix metalloproteinase expression and the plasma zinc levels. CONCLUSIONS: Women with fibroadenoma had hypozincemia and positive expression of metalloproteinases.

Evaluation of vitamin D receptor expression in uterine leiomyoma and nonneoplastic myometrial tissue: a cross-sectional controlled study.

BACKGROUND: Uterine myomas are the most frequent benign solid pelvic tumors in women of reproductive age. At present, uterine myomas are the most common indication for hysterectomy because of the morbidity they cause, including intense bleeding, compression of adjacent organs, pain, and infertility. Some studies show that vitamin D receptor (VDR) expression is correlated with the etiology of uterine leiomyomas. This study aimed to assess the expression of VDR in uterine leiomyoma and nonneoplastic myometrial tissue. METHODS: A controlled cross-sectional study involving 40 women who underwent abdominal hysterectomy the Department of Gynecology of the Getúlio Vargas Hospital of Federal University of Piauí, Brazil, was performed to compare the immunohistochemical expression of VDR in samples of uterine leiomyoma tissue with adjacent nonneoplastic myometrial tissue. The mean percetages of stained nuclei in the two groups was compared by Student's t teste, with significance established at p < 0.05. RESULTS: The percentage of cells with nuclei stained by anti-VDR in the myometrial and leiomyoma tissue was 79.52 % (± 4.32) and 60.22 % (± 7.24), respectively (p < 0.0001). CONCLUSIONS: The mean percentage of nuclei expressing VDR was significantly lower in the uterine leiomyoma than in nonneoplastic myometrial tissue.

Influence of CYP19A1 gene expression levels in women with breast cancer: a systematic review of the literature

Breast cancer is the most frequently diagnosed malignant neoplasm in women and is considered a multifactorial disease of unknown etiology. One of the major risk factors is genetic alteration. Changes in CYP19A1 gene expression levels have been associated with increased risk and increased aggressiveness of breast cancer. Increased CYP19A1 gene expression and/or aromatase activity are among the major regulatory events for intratumoral production of estrogens in breast malignant tissues. This systematic review aimed to investigate the influence of CYP19A1 gene expression levels in women with breast cancer. The research was carried out using the PubMed, Scopus, and Web of Science databases. Searches were conducted between February 2 and May 15, 2019. Inclusion criteria were studies published between 2009 and 2019, English language publications, and human studies addressing the gene expression of CYP19A1 in breast cancer. A total of 6.068 studies were identified through PubMed (n=773), Scopus (n=2,927), and the Web of Science (n=2,368). After selecting and applying the inclusion and exclusion criteria, six articles were included in this systematic review. This systematic review provides evidence that increased or decreased levels of CYP19A1 gene expression may be related to pathological clinical factors of disease, MFS, OS, DFS, WATi, markers of metabolic function, concentrations of E1, FSH, and in the use of multiple exons 1 of the CYP19A1 gene in breast cancer.

Human Epidermal Growth Factor Receptor-2 gene polymorphism and breast cancer risk in women from the Northeastern region of Brazil.

OBJECTIVES: In the Human Epidermal Growth Factor Receptor-2 (HER2) rs1136201 variant, the presence of the G allele may promote cellular alterations and increase breast cancer risk, in addition to enhanced cellular proliferation, tumor aggressiveness, and metastases. The aim of this study was to investigate the presence of the single-nucleotide polymorphism (SNP) variant, rs1136201, within the HER2 gene in women from the Northeastern region of Brazil and breast cancer risk. METHODS: The study included 140 women who were divided into two groups, case (breast cancer) and control (without breast cancer), with 70 women in each group. Peripheral blood of each woman was drawn for the study of genomic Deoxyribonucleic acid (DNA) extracted from leukocytes using the genotyping technique by real-time polymerase chain reaction. RESULTS: The GG genotype occurred in 1 woman in both groups (1.4%) (p=0.32), while the AG genotype occurred in 19 (27.2%) and 13 (18.6%) women in the case and control (p=1.00) groups, respectively. No statistically significant difference in GG and AG genotypes was observed between the case and control groups in premenopausal women (p=1.00). Furthermore, no significant difference in genotypes was observed between the groups, among postmenopausal women (p=0.14). CONCLUSION: In this study, the HER2 rs1136201 polymorphism did not show any statistically significant association with breast cancer, both in premenopausal and postmenopausal women. Nevertheless, further studies with a larger sample size should be performed to assess the association of HER2 polymorphism with breast cancer risk in women from the Northeastern region of Brazil.

Association between matrix metalloproteinase-9 gene polymorphism and breast cancer in Brazilian women.

OBJECTIVE: This study aimed to determine the relationship between rs17576 (MMP-9) polymorphism and increased cancer risk in a Brazilian breast cancer cohort. METHODS: This study included 141 women (71 breast cancer patients and 70 controls without breast cancer) who donated 3 mL of their peripheral blood for genomic DNA extraction. This DNA was then genotyped using a real-time polymerase chain reaction. RESULTS: The AG (rs17576) genotype was identified in 26 (18.43%) participants in the case group and in 22 (15.60%) participants in the control group (p=0.274), while the GG genotype was identified in ten (7.09%) participants in the case group and in one (0.70%) participant in the control group (p<0.003 - OR (95% CI) 13.13 (1.73, 593.08). No significant difference in the incidence rates was observed for AG or GG rs17576 genotypes in premenopausal women, p=0.813 and p=0.556, respectively. However, in postmenopausal women, the AG genotype was shown to occur in 14 (22.5%) participants in the case group and in 4 (6.45%) participants in the control (p<0.043), while GG genotype occurred in eight (12.90%) of the individuals in the case group and in none of the individuals in the control group (p<0.006). CONCLUSION: In this study, the MMP-9 rs17576 GG polymorphic variant was shown to be significantly associated with breast cancer risk in premenopausal women, while the AG and GG genotypes were associated with increased cancer risk in postmenopausal women.

Assessment of IGF-1 expression in the peripheral blood of women with recurrent breast cancer.

Breast cancer is the most common malignancy affecting women worldwide. The insulin-like growth factor 1 (IGF-1) gene encodes a protein responsible for a wide variety of physiological processes, including differentiation and cell proliferation. Despite several studies on tumor tissues, no study has evaluated IGF-1 expression in the peripheral blood of women with recurrent breast cancer.In this cross-sectional study, IGF-1 expression in the peripheral blood of 146 women with breast cancer treated approximately 5 years ago was quantified by quantitative reverse transcription polymerase chain. The women were divided into 2 groups: non-recurrence (n = 85) and recurrence (n = 61). Statistical analysis of the data was performed using ANOVA, Mann-Whitney, and Chi-squared tests (P < .05).The results showed no significant difference in IGF-1 expression between the non-recurrence and recurrence groups (P = .988). In the subgroups of patients with lymph node involvement, no statistically significant difference was observed in IGF-1 expression between women with recurrence and those non-recurrence (P = .113). In patients without lymph node metastases, IGF-1 messenger ribonucleic acid (mRNA) expression levels were significantly higher in the non-recurrence group than in the recurrence group (P = .019). Furthermore, using the median IGF-1 mRNA expression as the cutoff point, it was obtained a statistically significant difference in tumor histological grade among women with recurrent breast cancer (P = .042).These data showed significantly higher IGF-1 expression in women without lymph node metastases in the non-recurrence group compared with the recurrence group. In addition, a significant difference was observed in median IGF-1 mRNA expression in relation to tumor histological grade in women with recurrent breast cancer.

Evaluation of the accuracy of mammography, ultrasound and magnetic resonance imaging in suspect breast lesions.

OBJECTIVES: In breast cancer diagnosis, mammography (MMG), ultrasonography (USG) and magnetic resonance imaging (MRI) are the imaging methods most used. There is a scarcity of comparative studies that evaluate the accuracy of these methods in the diagnosis of breast cancer. METHODS: A cross-sectional study was carried out through the review of electronic medical records of 32 female patients who underwent breast imaging examinations at a imaging diagnostic center in Teresina, State of Piauí, Brazil. Patients who had these three imaging methods at the time of the evaluation of the same nodule were included. The nodule must have been classified as suspect by the BI-RADS® system in at least one of the methods. Data from each method were compared with the histopathological examination. Statistical analysis used the calculation of proportions in Excel 2010. RESULTS: MMG showed 56.2%, 87.5%, 81.8%, 66.7% and 71.8% of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy, respectively. USG had 75%, 18.8%, 48%, 42.8% and 46.9% of sensitivity, specificity, PPV, NPV and accuracy, respectively. In turn, MRI had 100%, 50%, 66.7%, 100% and 75% of sensitivity, specificity, PPV, NPV and accuracy, respectively. CONCLUSION: Thus, MRI and MMG were more accurate in evaluating suspicious breast lumps. MRI had a low specificity, mainly to high breast density, while MMG had also sensitivity limited due to high breast density and USG has been proven to be useful in these patients.

Expression of Nrf2 and NF-κB transcription factors in breast cancer and breast fibroadenoma: Insights for a new therapeutic approach.

Background: Cancer and fibroadenoma are the most common breast tumors in women of reproductive age. Nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor kappaB (NF-κB) transcription factor play an important role in the inflammatory process and in cell proliferation. However, few studies have analyzed these markers in breast cancer and fibroadenoma in women of reproductive age. Results: Light microscopy showed a higher concentration of anti-Nrf2 and anti-NF-κB-stained nuclei in breast cancer than in fibroadenoma. The mean percentage of stained nuclei for Nrf2 was 7.12 ± 5.2 and 43.21 ± 19.83 in the control and study groups, respectively (p < 0.0001). The mean percentage of anti-NF-κB was 10.75 ± 7.09 and 56.14 ± 21.19 (mean ± standard deviation) in the control and study groups, respectively (p < 0.0001). Histological grade 3 tumors showed a significantly higher expression of Nrf2 and NF-κB than grade 1 tumors (p < 0.05). Material and methods: This study was approved by the Institutional Review Board of Federal University of Piaui and all patients assigned an inform consent term prior to the study initiation. Nrf2 and NF-κB expression was evaluated by immunohistochemistry in 66 patients, divided into two groups, control (fibroadenoma, n = 36) and study (cancer, n = 30). The data were analyzed using ANOVA test and the statistical significance was established at p < 0.05. Conclusion: Nrf2 and NF-κB expression was significantly higher in breast cancer than in fibroadenoma, in addition to having a greater association with more aggressive tumors.

CYP19A1 gene expression in the peripheral blood of Brazilian women with breast cancer relapse.

BACKGROUND: The CYP19A1 gene, which encodes the enzyme responsible for androgen aromatization into estrogens, may play an important role in breast cancer aggressiveness. However, no study has evaluated CYP19A1 gene expression in the peripheral blood of women with relapsed breast cancer. METHODS: In this cross-sectional study, CYP19A1 gene expression was quantified by RT-PCR in the peripheral blood of 146 women with breast cancer who were first divided into two groups according to the expression of CYP19A1 (low and high); each group had 73 patients. Subsequently, women were divided into two groups: those without recurrence (control, n = 85) and those with recurrence (study, n = 61). Statistical analysis of the data was performed using ANOVA, the Mann-Whitney, Chi-square or Fisher's exact test (p <  0.05). RESULTS: There were no significant differences between the relative expression of CYP19A1 mRNA in the low expression group and the high expression group according to the variables studied. There were no significant differences in CYP19A1 gene expression in the study and control groups (p = 0.8461). In the relapse group, CYP19A1 gene expression was significantly higher in the hybrid luminal subtype than in the triple-negative subtype (p = 0.0321), whereas it was significantly lower in HER2-negative cases than in HER2-positive cases (p <  0.0376). Women with locoregional recurrence showed higher expression than women with distant recurrence (p <  0.0001). CONCLUSIONS: The present study found no significant differences between women with high and low expression of the CYP19A1 gene mRNA or between those in the study group and the control group. However, in women with recurrence, there was increased expression of CYP19A1 mRNA in those who had the luminal hybrid subtype and locoregional relapse and decreased expression in those negative for HER2.

Effects of anastrozole on Ki-67 antigen expression in the vaginal epithelium of female rats in persistent estrus.

OBJECTIVES: Aromatase inhibitors are the first-choice drugs for the treatment of hormone sensitive breast cancer. However, in addition to the scarcity of studies, there are controversies about their effects on vaginal epithelial cell proliferation in rats, especially those in persistent estrus. METHODS: To investigate vaginal epithelial cell proliferation by Ki-67 antigen expression, persistent estrus was induced in 42 randomly selected rats. These rats were randomly divided into 2 groups: group I (control, n=21), which received 0.1 mL of propylene glycol (vehicle) daily, and group II (experimental, n=21), which received 0.5 mg/kg or 0.125 mg/day of anastrozole diluted with 0.1 mL of propylene glycol. RESULTS: Light microscopy showed a higher concentration of cells with brown Ki-67 stained nuclei in the control compared to the experimental group. The mean percentage of Ki-67 stained nuclei per 500 cells in the vaginal epithelium was 68.64±2.64 and 30.46±2.00 [mean±standard error of the mean (SEM)] in the control and experimental groups, respectively (p<0.003). CONCLUSION: This study showed that anastrozole, at the dose and treatment duration selected, significantly decreased cell proliferation in the vaginal mucosa of the rats in persistent estrus.

Association between Single Nucleotide Polymorphisms and Glioma Risk: A Systematic Literature Review.

This study aimed to determine the main single nucleotide polymorphisms (SNPs) that are associated with an increased or decreased risk of glioma development in healthy individuals. We conducted a systematic review of the articles published in English on the PUBMED database between January 2008 and December 2017. Our search resulted in a total of 743 articles; however, only 56 were included in this review. A total of 148 polymorphisms were found, which involved 64 different genes. The polymorphisms that were most associated with an increased risk of glioma development were polymorphic variants rs179782, rs13181, and rs3791679 of the genes XRCC1, ERCC2, and EFEMP1, respectively.

Evaluation of the accuracy of mammography, ultrasound and magnetic resonance imaging in suspect breast lesions

OBJECTIVES: In breast cancer diagnosis, mammography (MMG), ultrasonography (USG) and magnetic resonance imaging (MRI) are the imaging methods most used. There is a scarcity of comparative studies that evaluate the accuracy of these methods in the diagnosis of breast cancer. METHODS: A cross-sectional study was carried out through the review of electronic medical records of 32 female patients who underwent breast imaging examinations at a imaging diagnostic center in Teresina, State of Piauí, Brazil. Patients who had these three imaging methods at the time of the evaluation of the same nodule were included. The nodule must have been classified as suspect by the BI-RADS® system in at least one of the methods. Data from each method were compared with the histopathological examination. Statistical analysis used the calculation of proportions in Excel 2010. RESULTS: MMG showed 56.2%, 87.5%, 81.8%, 66.7% and 71.8% of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy, respectively. USG had 75%, 18.8%, 48%, 42.8% and 46.9% of sensitivity, specificity, PPV, NPV and accuracy, respectively. In turn, MRI had 100%, 50%, 66.7%, 100% and 75% of sensitivity, specificity, PPV, NPV and accuracy, respectively. CONCLUSION: Thus, MRI and MMG were more accurate in evaluating suspicious breast lumps. MRI had a low specificity, mainly to high breast density, while MMG had also sensitivity limited due to high breast density and USG has been proven to be useful in these patients.