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.

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.

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.

Review of Polymorphism of the Calcium-Sensing Receptor Gene and Breast Cancer Risk.

Polymorphism of the calcium-sensing receptor gene (CaSR or CaR) has been associated with an increased risk for breast cancer. This receptor plays an important role in calcium homeostasis, and has also been detected in several tissues that are unrelated to calcium metabolism, such as the skin, brain, and breast. The calcium-sensing receptor on cellular level, it regulates cell differentiation, proliferation, cell death, and gene expression. In breast cancer cells, CaSR seems to stimulate secretion of the parathyroid hormone-related protein (PTHrP), which stimulates cellular proliferation. Likewise, some studies have supported not only an association between calcium receptor gene polymorphism and breast cancer risk, but also a higher aggressiveness and unfavorable outcomes in breast cancer, which led us to make a survey in Pubmed on the subject in the last 10 years. Thus, in the literature there is a paucity of studies on the subject and the aim of this review was to show the role of calcium-sensing receptor and its association with breast cancer risk.

A rare case of primary breast angiosarcoma in a male: a case report.

BACKGROUND: Sarcomas account for less than 1% of primary breast cancers, and breast angiosarcomas are responsible for only 0.05% of all breast malignancies. The male breast has the same potential for malignant transformation as the female breast. However, due to anatomical differences in the breast and the low incidence of angiosarcoma, it is difficult to determine how male breasts can be affected by this type of tumor. CASE PRESENTATION: A 36-year-old male patient was admitted to the hospital with a palpable lump in his right breast. Lymphadenopathy was negative. Ultrasonography showed a hypoechoic mass with partially defined contours, measuring 4.0 × 3.0 cm, with muscle infiltration. Histological examination revealed a malignant tumor. Radical mastectomy was then performed with clear surgical margins. The patient began chemotherapy with paclitaxel. Following the second cycle of chemotherapy, he presented with headache and seizures due to a frontal lobe metastasis. Twenty days after the onset of neurological symptoms, the patient died. CONCLUSIONS: Primary angiosarcomas of the male breast are extremely rare. This is the sixth case published in the literature. It is in agreement with other studies in the literature concerning clinical presentation and poor prognosis. Treatment consists in surgical removal of the tumor with clear margins and without axillary lymphadenectomy.

Ki-67 antigen expression in the mammary epithelium of female rats in persistent estrus treated with anastrozole.

OBJECTIVES: To evaluate Ki-67 antigen expression in mammary epithelium of female rats in persistent estrus treated with anastrozole. MATERIALS AND METHODS: Twenty-eight Wistar-Hanover female rats in persistent estrus induced by subcutaneous injection of 1.25 mg of testosterone propionate in the second day of life were randomly divided into two groups, control and experimental, with 14 animals each. The animals of control group received only the vehicle (propyleneglycol) and the animals of group experimental received 0.125 mg daily of anastrozole by gavage during 28 days. After 28 days of treatment, all animals were sacrificed and the first pair of abdominal-inguinal mammary glands was removed and fixed in 10% buffered formalin to investigate Ki-67 antigen expression by immunohistochemistry. RESULTS: The mean percentage of Ki-67-stained nuclei per 500 cells in the mammary epithelium was 76.97 ± 0.76 and 14.44 ± 2.02 [mean ± standard error of the mean (SEM)] in the control and experimental groups, respectively (p < 0.0001). CONCLUSIONS: Anastrozole treatment significantly reduced Ki-67 expression in the mammary epithelium of rats in persistent estrus.

Comparative study of tamoxifen and raloxifene on endometrial cell proliferation of female rats in persistent estrus.

OBJECTIVE: The objective of the study was to compare the effect of tamoxifen and raloxifene on the endometrium of female rats in persistent estrus, by Ki-67 protein expression. METHODS: The study comprised 60 Wistar-Hannover female rats in persistent estrus, induced by a single subcutaneous dose of 1.25 mg of testosterone propionate on the second day of age. At 90 days of life, the animals were randomly divided into 3 groups of 20 animals each. Group 1 (control), received only placebo; group 2, the animals were treated with tamoxifen, 250 µg/d; and group 3, the rats were treated with 750 µg/d of raloxifene by gavage during 30 days. Then, the animals were killed, and the endometrium was removed for immunohistochemical analysis of Ki-67 antigen expression. Statistical analysis was performed by ß regression model (P < 0.05). RESULTS: Mean percentages of Ki-67 protein expression in the endometrium of rats in persistent estrus were 43.21% ± 3.39%, 7.36% ± 0.95%, and 7.20% ± 0.76% in groups 1, 2 and 3, respectively (P < 0.001). There was no statistical difference between groups 2 and 3 (P = 0.7159). CONCLUSIONS: The present results indicate that, at the doses and during the time of treatment used, both tamoxifen and raloxifene induce atrophy in a similar way of endometrial epithelium of rats in persistent estrus.

Expression of Ki-67 and Bcl-2 biomarkers in normal breast tissue from women of reproductive age treated with raloxifene.

OBJECTIVE: To evaluate the effect of raloxifene on antigen expression of Ki-67 and Bcl-2 in normal breast tissue. MATERIALS AND METHODS: A randomized, double-blind study was conducted with 40 premenopausal women aged 18-40 years who had been diagnosed with fibroadenoma of the breast. The patients were divided into two groups: Group A (placebo, n = 20), and Group B (raloxifene 60 mg, n = 20).The medication was taken for 22 days initiating from the first day of the menstrual cycle. An excisional biopsy was performed on the 23rd day. At the time of biopsy, a sample of normal breast tissue was collected to evaluate protein expression of Ki-67 and Bcl-2. The Student's t test and Chi-square test were used for statistical data analysis and the significance level was established at 5%. RESULTS: The mean percentage of nuclei stained for Ki-67 was 22.16 ± 1.91 (p < 0.001) and 2.161 ± 0.181 in the control group and the raloxifene group. The expression of Bcl-2 was similar in both groups (p = 0.8888). CONCLUSIONS: Raloxifene treatment significantly reduced antigen expression of Ki-67, but failed to have any significant results on the Bcl-2 expression. Further studies are warranted to evaluate the mechanism of raloxifene on apoptosis in normal breast tissue.

Formation of DNA strand breaks in peripheral lymphocytes of rats after exposure to natural sunlight.

OBJECTIVE: This paper aims to evaluate the genotoxicity in peripheral blood lymphocytes of rats after exposure to sunlight at different time points of day in a tropical region of Brazil (5 degrees S, 42 degrees W). MATERIALS AND METHODS: Thirty Wistar-Hannover rats, three months old, were randomly divided into three groups of 10 animals each: Group I [control, without exposure to ultraviolet (UV) radiation], Group II (exposed to sunlight during 08:00 a.m. to 10:00 a.m.), and Group III (exposed to sunlight during 10:00 a.m. to 12:00 a.m.). After a week of exposure, peripheral blood samples were taken from the tail of these animals to prepare smears on two slides per animal. In 24 h after exposure to sunlight in Group III, a new collection was obtained to observe the repair activity. The alkaline comet assay was used in this study to evaluate the genotoxic activity of sunlight (P < 0.05). RESULTS: There was no statistical difference between Group I and II (P = 0.672). On the other hand, the exposure to sunlight in Group III showed genotoxic action in comparison to the other groups (P < 0.0001). Also, there was no significant repair in Group III R (P = 0.407). CONCLUSION: This study has shown a genotoxic potential of sunlight (UVA-B) in lymphocytes of mammals from 10:00 a.m. to 12:00 a.m., due to a higher intensity of UV in this tropical region.

No evidence for an association of human papillomavirus and breast carcinoma.

Breast cancer represents a serious public health problem worldwide, for its high incidence, morbidity, mortality, and its high cost treatment. It is known that breast cancer is a multifactorial disease, possessing various risk factors, among which include hormonal factors, genetic and environmental. The role of viruses in breast carcinogenesis is controversial. This study aims to evaluate the expression of HPV 6, 11, 16, and 18 by polymerase chain reaction (PCR) in invasive ductal breast carcinoma. We analyzed 90 women diagnosed with invasive ductal breast carcinoma, of which the extracted DNA was amplified, quantified and tested for DNA subtypes 6, 11, 16, and 18 by PCR. The research carried out in 79 samples of HPV DNA, proved negative. Our study demonstrates no association between the most prevalent types of HPV and breast cancer.

Evaluation of estrogen and progesterone receptors in non-neoplastic breast tissue of women of reproductive age exposed to tamoxifen and raloxifene: a randomized, double-blind study.

The objective of the present study was to compare the effects of tamoxifen and raloxifene in non-neoplastic breast epithelium. A randomized, double-blind study was carried out in 57 ovulatory, premenopausal women of 18-40 years of age, who had been diagnosed with fibroadenoma of the breast. The patients were divided into three groups: Group A: placebo, n=20; Group B: tamoxifen 20 mg/day, n = 21; and Group C: raloxifene 60mg/day, n=16. The study medication was given for 22 days starting on the first day of the menstrual cycle. On the 23rd day, the fibroadenoma was removed and a sample of non-neoplastic breast tissue was collected for immunohistochemical evaluation of estrogen and progesterone receptors. Comparison between the mean percentages of stained nuclei in the three groups was performed by analysis of variance and multiple comparisons, using Tukey's method to compare pairwise means, with significance established at P < 0.05. Exposition to tamoxifen or raloxifene resulted in a significant and similar reduction in the mean percentage of stained nuclei for estrogen and progesterone receptors (P<0.0001). Tamoxifen and raloxifene reduce progesterone and estrogen receptor alpha expression significantly and to a similar extent in the non-neoplastic breast tissue of women of reproductive age.

Ki-67 and Bcl-2 antigen expression in adenomatous colorectal polyps from women with breast cancer.

BACKGROUND: The aim of this study was to evaluate Ki-67 and Bcl-2 antigen expression in colorectal polyps from women with breast cancer. METHODS: A randomized, controlled study was carried out in 35 women, either with or without breast cancer, who had adenomatous colorectal polyps. The patients were divided into two groups: group A (without breast cancer; control group; n = 17) and group B (with breast cancer; study group; n = 18). Immunohistochemistry was performed on the colorectal polyps to evaluate Ki-67 and Bcl-2 antigen expression. Student's t-test and the chi(2) test were used for the statistical analysis of Ki-67 and Bcl-2 expression, respectively. Statistical significance was established as P < 0.05. RESULTS: The mean percentage of Ki-67-stained nuclei in groups A and B was 36.25 +/- 2.31 and 59.44 +/- 3.34 (+/- SEM), respectively (P < 0.0001), while the percentage of cases with cells expressing Bcl-2 in groups A and B was 23.5 and 77.8%, respectively (P < 0.001). CONCLUSIONS: In the present study, there was greater proliferative activity and greater expression of the antiapoptotic protein Bcl-2 in the colorectal polyps of women with breast cancer.

Evaluation of arterial blood pressure and renal sodium handling in a model of female rats in persistent estrus.

The aim of this study was to evaluate the arterial blood pressure and renal function of female rats in persistent estrus. Twenty-five female Wistar-Hannover rats were randomly divided into two groups: Group I (control, n = 15) and experimental (persistent estrus, n = 10). A tail-cuff system was used to measure blood pressure at 12 weeks of life. Parameters to evaluate renal function were taken into consideration. A significant increase in arterial pressure and a significant decrease in fractional sodium excretion were found in the androgenized animals compared to controls. There was no difference between the two groups with respect to glomerular filtration rate or in fractional potassium excretion. An increase in blood pressure and a reduction in fractional sodium excretion occur in female rats in persistent estrus.

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.

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.

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.

Evaluation of Ki-67 antigen expression in the zona reticularis of the adrenal cortex of female rats in persistent estrus.

BACKGROUND: Hyperandrogenism and chronic anovulation are basic characteristics of polycystic ovary syndrome (PCOS), and androgens from the adrenal glands play an important role in the hyperandrogenism. Our aim was to evaluate the proliferative activity in the zona reticularis cells of the adrenal cortex of female rats in persistent estrus, a model developed to mimic PCOS. METHODS: Forty-four female Wistar-Hannover rats were randomly divided into two groups: control (n = 17) and animals which received 1.25 mg testosterone propionate s.c. on the second day of life (n = 27). At 90 days of age, after confirmation of persistent estrus, the animals were sacrificed, and the adrenal glands were removed and fixed in 10% buffered formalin to investigate Ki-67 antigen (marker of proliferation) expression by immunohistochemical analysis. Student's t-test and Levene's test were used in the statistical analysis. RESULTS: The mean percentage of Ki-67-stained nuclei per 1000 cells in the zona reticularis of the adrenal cortex was 15.58 +/- 1.14 (SEM) and 51.59 +/- 1.81 in the control and persistent estrus animals, respectively (P < 0.001). CONCLUSIONS: Proliferative activity in the zona reticularis cells of the adrenal cortex of the androgenized female rats was significantly greater than that of the control animals.

Effects of raloxifene on Ki-67 and CD34 antigen expression in breast cancer.

BACKGROUND: The aim of this study was to evaluate the effect of raloxifene on CD34 and Ki-67 antigen expression in breast cancer specimens from postmenopausal women. METHODS: Sixteen postmenopausal patients with operable, stage II (>or=3 cm), estrogen receptor-positive breast cancer, who took 60 mg of raloxifene daily for 28 days, participated in this study. Immunohistochemistry was carried out in tumor samples prior to and following raloxifene treatment to evaluate CD34 and Ki-67 protein expression. Angiogenesis was quantified in 10 randomly selected fields per slide, and Ki-67-stained nuclei were counted in 1,000 cells per slide using an image capture and analysis system with 400x magnification. Student's t test for paired samples was used for the statistical analysis of data. Statistical significance was established at p < 0.05. RESULTS: The mean number of microvessels was 44.44 +/- 3.54 prior to raloxifene therapy and 22.63 +/- 1.61 following therapy (p < 0.001), and the mean percentage of Ki-67-stained nuclei was 19.28 +/- 1.61 and 12.13 +/- 1.48 prior to and following raloxifene treatment, respectively (p < 0.001). CONCLUSION: Raloxifene significantly reduces CD34 and Ki-67 protein expression in breast carcinoma in postmenopausal women.

Expression of matrix metalloproteinase 2 and 9 in breast cancer and breast fibroadenoma: a randomized, double-blind study.

BACKGROUND: Matrix metalloproteinases (MMPs) 2 and 9 may play an important role in cell proliferation and dissemination of cancer. However, few studies have compared the expression of these proteins between breast cancer and fibroadenoma. MATERIAL AND METHODS: A randomized, double-blind study was carried out in 66 premenopausal women, aged 20-49 years, who had been diagnosed with fibroadenoma or breast cancer. The patients were divided into two groups: Group A, control (fibroadenoma, n=36) and Group B, study (cancer, n=30). Immunohistochemical analysis was performed using tissue samples of fibroadenoma and breast cancer to assess MMP-2 and MMP-9 antigen expression. Cells were considered positive if exhibiting brown cytoplasmic staining. Fisher's exact test was used to compare the percentage of cases with cells expressing MMP-2 and MMP-9 in control and study groups (p < 0.05). RESULTS: Light microscopy showed a higher concentration of cells with positive cytoplasmic staining for MMP-2 and MMP-9 expression in breast cancer than in fibroadenoma. The percentage of cases with cells expressing MMP-2 in the control and study groups was 41.67% and 86.11%, respectively (p < 0.0009), whereas the percentage of cases with cells expressing MMP-9 in groups A and B was 66.67% and 93.33%, respectively (p<0.0138). MMP-2 and MMP-9 positive expression was significantly higher in moderately differentiated tumors compared to well and poorly differentiated tumors, p <0.005 and p<0.001, respectively. CONCLUSIONS: The current study shows that MMP-2 and MMP-9 protein expression was significantly higher in the breast cancer than in the fibroadenoma and also in moderately differentiated breast cancer.