Progesterone Receptor Content Research Articles

Evaluation of Serum Hormones and Biochemical Tumor Markers among Breast Cancer Patients in the South-South Region, Nigeria

Breast cancer remains one of the most frequent malignancies in women and the primary cause of cancer-related death in women all over the world. Hormones and tumor biomarkers have been implicated as possible causes and prognostic biomarkers of breast cancer. The present study investigated the use of serum hormonal levels and tumor biomarkers; Carcinoembrvonic antigen (CEA), and cancer antigen (CA 15-3) for the diagnosis of Breast Cancer, and generation of different subtypes using Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This study is a cross-sectional study comprising 120 subjects; sixty breast cancer patients, and sixty apparently healthy women who served as control. One hundred and twenty blood samples were collected and analyzed for estrogen, progesterone, Carcinoembrvonic antigen, and cancer antigen. The results showed that the peak age of incidence of breast cancer was 40-49 years. Majority (56.7%) of the cases were menopausal women, while 43.3% were in their premenopausal period. Serum estrogen, cancer antigen, and Carcinoembrvonic antigen concentrations were elevated significantly (p<0.05) in the breast cancer patients than the control group. Premenopausal patients have higher progesterone, estradiol, Carcinoembrvonic antigen, and cancer antigen levels than those during the postmenopausal period. HER2 negative subtype (50.0%) is the most prevalent subtype of breast cancer. 8.4% were triple negative (ER–/PR–/HER2–) cases, while 1.7% were triple positive (ER+/PR+/HER2+) cases. Breast cancer is strongly associated with hormonal changes especially estrogen and progesterone during the premenopausal and postmenopausal periods in women. Thus, the determination of the concentration of estrogen, progesterone, Carcinoembrvonic antigen, cancer antigen, and human epidermal growth factor receptor 2 statuses could help in the prognosis of breast cancer.

Investigation of the infertility structure and outcomes of ART programs in patients of late reproductive age

Purpose: comparative study of the structure of infertility and outcomes of ART programs among patients of different age groups. Materials and methods: the case histories of 180 patients with infertility were studied: Group I ≥ 35 years old; Group II <35 years old. Laboratory and immunohistochemical studies were carried out, and the outcomes of ART were assessed. Results: in group I, a shortened menstrual cycle was determined in comparison with group II (27,15 ± 3,39 days vs 29,57 ± 2,38 days, p = 0,001). Also, in group I, the following were more often found: inflammatory diseases (p = 0,05); history of unilateral tubectomy (p = 0,019); increased FSH levels (9,73 ± 2,43 vs 8,74 ± 2,50); decrease in the concentration of LH, progesterone, AMH (p <0,05). In the cells of the aspirate of the uterine cavity in patients of group I, there was an increased content of progesterone receptors and a decreased concentration of estrogen receptors (p <0,05). Patients of group I received a smaller number of oocytes (8,34 ± 3,51 vs 10,78 ± 4,37) and quality embryos by the 5th day of cultivation (82,7% vs 87,97%; p <0,05). The number of pregnancies in groups I and II was 22,22% and 36,67%, respectively, and live births – 14,44% and 27,78% (p <0,05). Patients who gave birth had increased progesterone levels, greater endometrial thickness, more oocytes with transvaginal puncture, and high-quality embryos. Conclusion: the factors that reduce fertility were: genital pathology, inhibition of ovarian function, depletion of the follicular reserve. Fewer live births are associated with defects in embryonic and implantation factors.

Endocrine disruptor hexachlorobenzene induces cell migration and invasion, and enhances aromatase expression levels in human endometrial stromal cells

Endometriosis is the presence and growth of endometrial tissue outside of the uterus. Previous studies have suggested that endocrine disrupting chemicals such as organochlorine pesticides could be a risk factor for endometriosis. Hexachlorobenzene (HCB) is a weak ligand of the aryl hydrocarbon receptor (AhR) and promotes metalloproteinase and cyclooxygenase-2 (COX-2) expression, as well as, c-Src activation in human endometrial stromal cells (T-HESC) and in rat endometriosis model. Our aim was to evaluate the effect of HCB exposure on oestrogen receptor (ER) ɑ and β, progesterone receptor (PR) and aromatase expression, as well as, on cell migration and invasion in T-HESC and primary cultures of endometrial stromal cells from eutopic endometria of control subjects (ESC). Results show that HCB increases ERɑ and aromatase protein levels and reduces PR content in both T-HESC and ESC. However, the pesticide only increases ERβ expression in ESC, without changes in T-HESC. Moreover, cell migration and invasion are promoted by pesticide exposure involving the AhR, c-Src, COX-2 and ER pathways in T-HESC. HCB also triggers ERɑ activation via phosphorylation in Y537 through AhR/c-Src pathway. Our results provide experimental evidence that HCB induces alterations associated with endometriosis, suggesting that these mechanisms could contribute to pesticide exposure-induced endometriosis development.

Pathobiologic Stratification of Oncotype DX Recurrence Scores and Comparative Validation of 3 Surrogate Models.

The Oncotype DX Recurrence Score (RS) predicts recurrence and chemotherapy benefit in early-stage estrogen receptor-positive breast cancer patients. Cost and unavailability are 2 major disadvantages of the assay. Multiple models have been developed to predict the RS. To predict RS based on histopathologic and biomarker features, and to measure concordance and correlation with RS of the following 3 algorithms: breast cancer prognostic score, Magee0, and Magee2. Breast cancer cases with available RSs were reviewed (n = 442). RS categories were stratified by pathologic and biomarker variables. Histopathologic and biomarker data were abstracted from pathology reports, and RS was calculated by each model. Correlation and concordance between models and RS were calculated. Less than 5% of breast cancers with lobular features, low-grade tumors, carcinomas with high progesterone receptor content, or luminal A tumors had an RS greater than 25. Breast cancer prognostic score, Magee0, and Magee2 demonstrated correlation coefficients with RS of 0.63, 0.61, and 0.62, respectively. Two-step discordances were uncommon. When an RS of 25 was used to separate high-risk from non-high-risk cases, concordance rates of 86% to 88% were achieved. High RS was observed only in a small percentage of pure or mixed lobular carcinomas, low-grade or luminal A tumors, and tumors with high progesterone receptor expression, suggesting that these cancers may not require Oncotype testing. All 3 surrogate models demonstrated comparable correlation and high concordance with the RS when a cutoff of 25 was used, suggesting their utility in cases where the actual RS is unavailable.

Influence of progestational stress on BDNF and NMDARs in the hippocampus of male offspring and amelioration by Chaihu Shugan San

BackgroundProgestational stress has been proven to be a risk for the neural development of offspring, especially in the hippocampus. However, whether Chaihu Shugan San (CSS) can ameliorate hippocampal neural development via the regulation of brain-derived neurotrophic factor (BDNF), and N-methyl-D-aspartate receptors (NMDAR) 2A (NR2A) and 2B (NR2B), and the mechanism of such action remains unclear. MethodsThirty-six female rats were randomly allocated into control, chronic immobilization stress (CIS) and CSS groups according to the random number table, respectively. The male offspring were fed for 21 days after birth then randomly divided into the same three groups (6 rats/group) as the female rats. Female rats, except for the control group, underwent 21-day CIS to established a progestational stress anxiety-like model which was evaluated by body weight, the elevated plus-maze (EPM) test and serum dopamine (DA) measured using an enzyme-linked immunosorbent assay (ELISA). The expression levels of estrogen receptors (ERα/ERβ) and progesterone receptor (PR) in female rat ovaries were quantified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The hippocampal tissue in the 21-day offspring was observed by hematoxylin-eosin (HE) staining. The concentration of BDNF, NR2A, and NR2B were measured by RT-qPCR and immunohistochemistry in the CA3 and dentate gyrus (DG) regions of offsprings’ hippocampus. ResultsCompared with the female control group, significant differences in body weight, EPM test and DA concentration were observed in the CIS group, meanwhile, the concentration of ERα (P < 0.05), PR (P < 0.05) and ERβ in the ovaries were decreased. In the offsprings’ hippocampus of the CIS group, the chromatin of the nucleus was edge set and with condensed and irregular morphology nucleus, and the cytoplasm was unevenly stained with spaces around the cells, moreover, the expression levels of BDNF, NR2A, and NR2B were also declined (P < 0.05). However, Chaihu Shugan San reversed these changes, especially the BDNF in the DG region (P < 0.05), and NR2A and NR2B in the CA3 and DG region (P < 0.05). ConclusionsCSS could ameliorate the neural development of the hippocampus in offspring damaged by anxiety-like progestational stress in female rats via regulating the expression levels of ERα, ERβ, and PR in female rat ovaries and BDNF, NR2A, and NR2B in the hippocampus of their offspring.

Comparison of Clinico-Pathological Presentations of Triple-Negative versus Triple-Positive and HER2 Iraqi Breast Cancer Patients.

BACKGROUND:Breast cancer remains the most common malignancy among the Iraqi population. Affected patients exhibit different clinical behaviours according to the molecular subtypes of the tumour.AIM:To identify the clinical and pathological presentations of the Iraqi breast cancer subtypes identified by Estrogen receptors (ER), Progesterone receptors (PR) and HER2 expressions.PATIENTS AND METHODS:The present study comprised 486 Iraqi female patients diagnosed with breast cancer. ER, PR and HER2 contents of the primary tumours were assessed through immunohistochemical staining; classifying the patients into five different groups: Triple Negative (ER/PR negative/HER2 negative), Triple Positive (ER/PR positive/HER2 positive), Luminal A (ER/PR positive/HER2 negative), HER2 enriched ((ER/PR negative/HER2 positive) and all other subtypes.RESULTS:The major registered subtype was the Luminal A which was encountered in 230 patients (47.3%), followed by the Triple Negative (14.6%), Triple Positive (13.6%) and HER2 Enriched (11.5%). Patients exhibiting the Triple Negative subtype were significantly younger than the rest of the groups and presented with larger size tumours. A significant difference in the distribution of the breast cancer stages was displayed (p < 0.05); the most advanced were noted among those with HER2 enriched tumours who exhibited the highest frequency of poorly differentiated carcinomas and lymph node involvement.CONCLUSION:The most significant variations in the clinicopathological presentations were observed in the age and clinical stage of the patients at diagnosis. Adoption of breast cancer molecular subtype classification in countries with limited resources could serve as a valuable prognostic marker in the management of aggressive forms of the disease.

Tibolone Effects on Human Glioblastoma Cell Lines

Ovarian steroid hormones are involved in modulating the growth of glioblastomas (the most common, aggressive, and lethal brain tumor) through the interaction with their intracellular receptors. Activation of sex hormone receptors is involved in glioblastomas progression. Tibolone (TIB) is a selective tissue estrogenic activity regulator widely prescribed to treat menopausal symptoms and to prevent bone lost. The effects of TIB on the growth of glioblastoma are unknown. To evaluate the effects of TIB on cell number, migration, and invasion of two derived human glioblastoma cell lines (U251MG and U87), as well as the role of this steroid in estrogen and progesterone receptors activity and content. U251-MG and U87 human glioblastoma cell lines were grown with different doses of TIB. The number of cells was determined and migration and invasion tests were carried out. Protein expression was performed by Western blot. We observed that TIB (10nM) increased the number of cells by inducing proliferation with no effects on cell migration or invasion. The increase in cell proliferation induced by TIB was blocked by estrogen (ERs) or progesterone receptor (PRs) antagonists, ICI 182, 780 and RU 486, suggesting that these receptors mediate proliferating actions of TIB; TIB also modified the content of ERs and PRs by increasing ER-α, ER-β, and PR-B, while decreased PR-A. Our results suggest that TIB increases cell number and proliferation of human glioblastoma cells through the regulation of ERs and PRs actions and content.

Study on the regulatory mechanism of electroacupuncture based on thyroid pathway for mammary gland hyperplasia rats

To study the regulating effect of thyroid pathway on electroacupuncture (EA) for mammary gland hyperplasia (MGH) so as to provide new research ideas for the mechanism of EA for MGH and to provide the evidence for clinical application. Sixty adult female SD rats were randomly divided into a blank group, a model group, an EA group, an EA with thyroidectomy group, an EA with sham operation group, 12 rats in each one. Except the blank group, the MGH model was established. Thyroid ablation was performed in the EA with thyroidectomy group, and sham operation was used in the EA with sham operation group, exposing thyroid without excision, 1 day after model establishment. EA was applied in the EA, the EA with thyroidectomy, and the EA with sham operation groups on the 4th day after model establishment, and not used in the other groups, but catching, routine disinfection and fixation were all the same as the above groups. The acupoints in the group A were bilateral "Tianzong" (SI 11), "Ganshu" (BL 18) and "Zusanli" (ST 36); and those in the group B were bilateral "Wuyi" (ST 15), "Hegu" (LI 4) and "Danzhong" (CV 17). The two groups of points were alternately used. EA, continuous wave, 2 Hz and 1 mA, was connected at "Tianzong" (SI 11) and "Ganshu" (BL 18), "Wuyi" (ST 15) and "Hegu" (LI 4) at the same side, 2 pairs EA a time, 20 min a time, once a day. All the intervention was given for 4 courses, 5 times as 1 course with 2 days between courses. After intervention, the height and diameter of the rat papilla were measured. Estrogen (E2) and progestational hormone (P) in the serum were detected by enzyme linked immunosorbent assay (ELISA), and the contents and protein expression of estrogen receptor α (ERα) and progesterone receptor (PR) in the mammary glands were detected by immunofluorescence and Western-blot. (1) The height and diameter of papilla in the model group increased compared with those in the blank group (both P<0.01). The height and diameter of papilla in the EA, EA with sham operation groups reduced compared with those in the model group (all P<0.01). Those in the EA with thyroidectomy group were lower than those in the model group, without statistical significance (both P>0.05). (2) Compared with the blank group, E2 increased and P decreased in the model group (both P<0.01). Compared with the model group, E2 decreased and P increased in the EA and EA with sham operation groups (all P<0.01). The contents of E2 and P had no statistical significance between the model and the EA with thyroidectomy groups (both P>0.05). (3) Compared with the blank group, the ERα content and protein expression increased and the PR content and protein expression decreased in the model group (all P<0.01). Compared with the model group, the ERα content and protein expression decreased and the PR content and protein expression increased in the EA and EA with sham operation groups (all P<0.01). The ERα and PR content and protein expression had no statistical significance between the model and the EA with thyroidectomy groups (all P>0.05). The effect of EA for MGH may be closely related to the regulation of thyroid.

Comparative Study on the Clinicopathological Profiles of Breast Cancer Among Iraqi and British Patients

Background:Breast cancer is the most common cancer in Iraq and the United Kingdom. While the disease is frequently diagnosed among middle-aged Iraqi women at advanced stages accounting for the second cause of cancer-related deaths, breast cancer often affects elderly British women yielding the highest survival of all registered malignancies in the UK.Objective:To compare the clinical and pathological profiles of breast cancer among Iraqi and British women; correlating age at diagnosis with the tumor characteristics, receptor-defined biomarkers and phenotype patterns.Methods:This comparative retrospective study included the clinical and pathological characteristics of (1,940) consecutive female patients who were diagnosed with invasive breast cancer from 2014 to 2016 in Iraq (Medical City Teaching Hospital, Baghdad: 635 cases) and UK (John Radcliffe, Oxford and Queen's, BHR University Hospitals: 1,305 cases). The studied parameters in both groups comprised the age of the patient at the time of diagnosis, breast cancer histologic type, grade, tumor size, lymph node status, clinical stage at presentation, Estrogen Receptor (ER), Progesterone Receptor (PR) and HER2 positive tumor contents and the receptor-defined breast cancer surrogate subtypes.Results:The Iraqi patients were significantly younger than their British counterparts and exhibited higher trend to present at advanced stages; reflected by larger size tumors and frequent lymph node involvement compared to the British (p&lt;0.00001). They also had worse receptor-defined breast cancer subtypes manifested by higher rates of hormone receptor (ER/PR) negative, HER2 positive tumor contents, Triple Positive and Triple Negative phenotypes (p&lt;0.00001). Excluding HER2 status, the significant differences in the clinical and tumor characteristics between the two populations persisted after adjusting for age among patients younger than 50 years.Conclusion:The remarkable differences in the clinical and tumor characteristics of breast cancer between the Iraqi and British patients suggest heterogeneity in the underlying biology of the tumor which is exacerbated in Iraq by the dilemma of delayed diagnosis. The significant ethnic disparities in breast cancer profiles recommend the prompt strengthening of the national cancer control plan in Iraq as a principal approach to the management of the disease.

Immunohistochemical Study of Hormonal Receptors in Endometrium of Women with Dysfunctional Uterine Bleeding: A Two Year Experience of a Tertiary Care Center

Dysfunctional uterine bleeding is a major gynecologic problem, with varied treatment options. A significant proportion of these patients undergo hysterectomy. To investigate the hormonal milieu at tissue level, we semiquantitatively assessed the estrogen and progesterone receptors in the endometrial samples of 50 DUB patients, by Immunohistochemistry. We observed a significant increase (p<0.001) in the concentration of both estrogen and progesterone receptors in patients with dysfunctional uterine bleeding, compared to normal population. We also noted a significant increase in the endometrial thickness (p<0.001) of patients with simple endometrial hyperplasia. Our study demonstrates the role of estrogen and progesterone receptors in the etiopathogenesis of dysfunctional uterine bleeding and in the alteration in the morphology of endometrium, such as simple endometrial hyperplasia. We advocate the use of progesterone antagonists and selective progesterone receptor modulators in the treatment of patients with dysfunctional uterine bleeding, especially in those with endometrial hyperplasia, who carry the long term risk of endometrial carcinoma with sustained endometrial estrogenic stimulation.

Expression of sex hormone receptors in the brain of male and female newly hatched chicks

Chromosomal sex and steroid hormones play a determining role in brain sexual differentiation during chick embryonic development. Hormone effects on the brain are associated with the expression pattern of their intracellular receptors, which is sexually dimorphic in many species. We determined by Western blot the content of progesterone, estrogen, and androgen receptors (PR-A and PR-B, ERα, and AR, respectively) in the cortex, cerebellum, tectum, and hypothalamus of female and male newly hatched chicks. Males presented a higher content of PR-B in the tectum whereas females exhibited a higher content of PR-A in the hypothalamus. ERα was only detected as a band of 66kDa, and it showed a higher content in the cerebellum and tectum of females as compared to these regions in males. Besides, males exhibited a higher content of AR in the tectum than females. Our study suggests that newly hatched chicks show a sexual dimorphism in the expression of sex hormone receptors in brain regions involved in sexual behavior such as the hypothalamus, and in non-sexual behavior such as the optic tectum and the cerebellum.

Abstract 673: Exploration of tissue morphologies in breast cancer samples using unsupervised machine learning

Abstract We applied a machine learning approach for exploration of tissue morphology in hematoxylin and eosin (H&amp;E) stained breast cancer tissue microarray (TMA) samples. We then investigated whether the morphological categories produced were associated with clinically relevant molecular biomarkers and 10-year overall survival. The data set comprises digitized (0.22 µm/pixel) and H&amp;E stained TMA spots from tumor samples of 490 women who were diagnosed with primary breast cancer within a Finnish breast cancer database (FinProg) collected in 1991 and 1992. In order to quantitatively describe the tissue morphologies of the TMA spots, we divided the tissue images into rectangular sub-images (224x224 pixels), and extracted features with a pre-trained convolutional neural network. We then clustered the sub-images (n=147,266) with a non-linear data embedding algorithm that creates a two-dimensional mapping of the tissue morphologies. Lastly, we defined a quantitative profile for each tumor, describing the morphologies within the tissue spot image by dividing the two-dimensional map of morphologies into 128 separate clusters with k-nearest neighbor clustering. Visual inspection of the two-dimensional embedding of tissue spot images verified that the morphologies clustered coherently, i.e. similar looking sub-images formed distinct clusters in the map. Interestingly, some morphological patterns were strongly associated with tumor estrogen receptor content, progesterone receptor content, human epidermal growth factor receptor 2 status, and the proliferation marker Ki-67 status (p&amp;lt;0.0001 for each comparison). In exploratory analyses we identified one morphological category that was associated with a favorable 10-year overall survival with a risk ratio of 0.68 (CI95% 0.53-0.89, p=0.002, power = 0.87). Our work demonstrates that unsupervised machine learning can be applied to explore and better understand the role of morphological patterns in breast cancer. Methods that quantitatively assess the morphology of cancer tissue may complement molecular biomarkers and potentially reveal novel prognostic and predictive factors. Citation Format: Riku Turkki, Dmitrii Bychkov, Nina Linder, Jorma Isola, Heikki Joensuu, Johan Lundin. Exploration of tissue morphologies in breast cancer samples using unsupervised machine learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 673. doi:10.1158/1538-7445.AM2017-673

Adjuvant Capecitabine in Combination With Docetaxel, Epirubicin, and Cyclophosphamide for Early Breast Cancer

Capecitabine is not considered a standard agent in the adjuvant treatment of early breast cancer. The results of this study suggest that addition of adjuvant capecitabine to a regimen that contains docetaxel, epirubicin, and cyclophosphamide improves survival outcomes of patients with triple-negative breast cancer (TNBC). To investigate the effect of capecitabine on long-term survival outcomes of patients with early breast cancer, particularly in subgroups defined by cancer estrogen receptor (ER) and progesterone receptor (PR) content, and HER2 content (human epidermal growth factor receptor 2). This is an exploratory analysis of the multicenter FinXX randomized clinical trial that accrued 1500 women in Finland and Sweden between January 27, 2004, and May 29, 2007. About half received 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (T+CEF), while the other half received 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (TX+CEX). Data analysis took place between January 27, 2004, and December 31, 2015. Recurrence-free survival (RFS). Following random allocation, 747 women received T+CEF, and 753 women received TX+CEX. Five patients were excluded from the intention-to-treat population (3 had overt distant metastases at the time of randomization; 2 withdrew consent). The median age of the remaining 1495 patients was 53 years at the time of study entry; 157 (11%) had axillary node-negative disease; 1142 (76%) had ER-positive cancer; and 282 (19%) had HER2-positive cancer. The median follow-up time after random allocation was 10.3 years. There was no significant difference in RFS or overall survival between the groups (hazard ratio [HR], 0.88; 95% CI, 0.71-1.08; P = .23; and HR, 0.84, 95% CI, 0.66-1.07; P = .15; respectively). Breast cancer-specific survival tended to favor the capecitabine group (HR, 0.79; 95% CI, 0.60-1.04; P = .10). When RFS and survival of the patients were compared within the subgroups defined by cancer steroid hormone receptor status (ER and/or PR positive vs ER and PR negative) and HER2 status (positive vs negative), TX+CEX was more effective than T+CEF in the subset of patients with TNBC (HR, 0.53; 95% CI, 0.31-0.92; P = .02; and HR, 0.55, 95% CI, 0.31-0.96; P = .03; respectively). Capecitabine administration with docetaxel, epirubicin, and cyclophosphamide did not prolong RFS or survival compared with a regimen that contained only standard agents. Patients with TNBC had favorable survival outcomes when treated with the capecitabine-containing regimen in an exploratory subgroup analysis. clinicaltrials.gov Identifier: NCT00114816.

Clinical significance of oestrogen and progesterone receptors in the growth and symptomatology of uterine fibroids

Background : Uterine fibroids are responsible for significant morbidity in a large proportion of the female population of the reproductive age worldwide. Hence, there is a need to determine the levels of oestrogen and progesterone receptors in relation to the growth and symptomatology in a purely African population noted for high incidence of uterine fibroids. Objectives : To determine the levels of oestrogen and progesterone receptors in normal myometrium and uterine fibroids and ascertain whether there are any significant clinical associations. Materials and Methods : This was a prospective study conducted at the Obstetrics and Gynaecology Department in collaboration with the Morbid Anatomy Department, both at the University of Benin Teaching Hospital (UBTH). Tissue specimens obtained from uterine fibroids and normal myometrium during surgeries performed on patients with a pre‑operative diagnosis of uterine fibroids were histologically examined. The concentrations of oestrogen and progesterone receptors were histochemically determined for the selective tissue slides. The results and the socio‑demographic characteristics of the patients were used to generate a database for analysis. Results : A total of 262 cases of uterine fibroids were analysed. Those presenting with lower abdominal mass had more oestrogen receptors in uterine fibroids (57.0%, P = 0.014), whereas more progesterone receptors were found in those presenting with menorrhagia (P = 0.001). A comparison of oestrogen and progesterone receptors in uterine fibroids and normal myometrium showed significantly higher levels of oestrogen and progesterone receptors in fibroids than in normal myometrium (P = 0.000). Conclusion : The concentrations of oestrogen and progesterone receptors in uterine fibroids were significantly higher than those in normal myometrium. The steroid dependence of the growth and symptomatology of uterine fibroids may be related to the steroid receptor level. Identification and quantification of the concentrations of oestrogen and progesterone receptors will be useful in the prognostication and the development of newer treatment modalities for uterine fibroids. Further research in this area is clearly warranted. Key words : Myometrial tissues; oestrogen receptors; progesterone receptors; uterine fibroids; University of Benin Teaching Hospital.

The Stage of Breast Cancer at the Time of Diagnosis: Correlation with the Clinicopathological Findings among Iraqi Patients

Background: Breast cancer is the most frequently diagnosed malignancy and the second leading cause of mortality among women in Iraq forming 23% of cancer related deaths. The low survival from the disease is a direct consequence to the advanced stages at diagnoses. Aim: To document the composite stage of breast cancer among Iraqi patients at the time of diagnosis; correlating the observed findings with other clinical and pathological parameters at presentation. Patients and Methods: A retrospective study enrolling the clinical and pathological characteristics of 603 Iraqi female patients diagnosed with breast cancer. The composite stage of breast cancer was determined according to UICC TNM Classification System of Breast Cancer and the American Joint Committee on Cancer Staging. The studied parameters comprised age of the patient, stage of the disease, marital and educational status, history of lactation and hormonal intake (for a minimum period of 6 months), family history of breast or any other cancer, the effected breast side, hormone (Estrogen and Progesterone) receptor (ER, PR) and Her2 contents of the primary cancer. Statistical analysis was performed to correlate the recorded composite stages at diagnosis with the corresponding clinical and pathological data utilizing SPSS version 16.0 statistical program. Results: Out of 603 patients, seven (1.2%) had ductal carcinoma in situ (Stage 0). Stages I, II and III and IV were documented in 9.5%, 47.1%, 33.2% and 9.1% of the patients at the time of diagnoses. Overall 70.8% of patients presented in the age group (40-59 years), 79.3% were married and 32.2% were highly educated. History of lactation, hormonal intake, family breast cancer and contralateral breast involvement was observed in 73.4%, 26.5%, 20.2% and 6.5% respectively. No correlation was elicited between the stage of breast cancer and the age of the patients, history of lactation or contralateral breast involvement. On the other hand, significant associations were demonstrated with respect to the marital and educational status, history of hormonal intake and breast cancer in the family. Immuno-histochemical evaluation revealed ER+PR+Her2+ (Triple Positive/Luminal B), ER-PR-Her2- (Triple Negative), ER+PR+Her2- (Luminal A) and ER-PR-Her2+ (Her2) subtypes in 13.4%, 11.8%, 48.2% and 9.8% of the examined breast samples respectively. When correlating the composite stage at diagnosing breast cancer with the corresponding subtypes the relationship was highly significant at p<0.01. Conclusions and Recommendations: The study reports a regression in Stage IV breast cancer at the time of initial presentation among Iraqi patients specifically in those with family history of the disease; pointing out to the fruitful outputs of initiating the National Program for Early Detection of Breast Cancer in the country. Further professional efforts, endorsed by practical policy decisions, are recommended to down stage breast cancer through promoting evidence based protocol guidelines and adopting comprehensive well designed diagnostic, screening and cancer control strategies.

The reduced content of estrogen and progesterone receptors in varicocele sperm may be indicative of the clinical surgery in the testicular varicocele

The enigma of testicular varicocele has always attracted the researcher’s attention as attested by the consistent literature, although conflicting data are reported (1). The detrimental role of varicocele in fertility is supported by the presence of an higher frequency of affected men in the infertile population (2). Varicocele influences male fertility in a variety of ways: spermatogenesis, semen quality and gamete biology. However, the mechanism/s by which the pathology impairs sperm production and activity, are not known yet. In spite of active interest, our knowledge about sperm molecular anatomy is very limited. Instead, it is important to fully elucidate the molecular sperm architecture, in order to clarify clinical cases of idiopathic infertility since not all the apparently normal sperm are able to fertilize. The presence of steroid/steroid receptor systems was demonstrated in human sperm, suggesting that both systemic and local steroids through sperm receptors, may influence male fertility. From our data, it emerged that varicocele causes a damage in the gamete at molecular level which includes a significant reduction of estrogen and progesterone receptors, opening a new chapter in the already multifaceted physiopathology of the disease. By the time of ovulation, estradiol and progesterone are almost everywhere in the egg microenvironment affecting ability of sperm to fertilize the oocyte. Therefore, the reduced responsiveness to these hormones as we observed in varicocele sperm, impedes their goal. Altogether, these studies constrain the need of further researches on the molecular anatomy of human male gamete both in healthy and in pathological conditions related the male genital apparatus, considering the high couple infertility linked to the male. The translation of these new researches in the clinic surgery of testicular varicocele needs to be taken into account since the reduction of steroid receptors in sperm implies a decline in the acquisition of fertilizing ability.

Long intergenic non-coding RNAs (LincRNAs) identified by RNA-seq in breast cancer.

In an attempt to find the correlation of aberrant expression of long intergenic noncoding RNAs (lincRNAs) with cancer, twenty-five samples of breast cancer tissue and respective adjacent normal tissue were studied for the expression of lincRNAs by RNA-seq. Among the 538 lincRNAs studied, 124 lincRNAs were exclusively expressed in cancer adjacent tissues and 62 lincRNAs were exclusively expressed in the cancer tissues. Furthermore, the expression of 134 lincRNAs was higher while 272 lower in breast cancer tissue compared with adjacent tissue. The expression of four selected lincRNAs (BC2, BC4, BC5, and BC8) was validated by semi-quantitative and real-time PCR. It was revealed that expression of lincRNA-BC5 was positively correlated with patients' age, pathological stage, and progesterone receptor concentration, while lincRNA-BC8 was negatively correlated with progesterone receptor expression. Higher expression of lincRNA-BC4 was seen in advanced breast cancer grade. LincRNA-BC2 showed no specific changes in the pathological features studied. Interactions between selected lincRNAs and breast cancer associated proteins were highly suggested by RPIseq based on the specific secondary structure. The results demonstrated that this group of lincRNAs was aberrantly expressed in breast cancer. They might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of breast cancer.

Estrogen and progesterone receptors in endometrium in women with unexplained infertility.

Aim:The purpose of the present study is to evaluate the relationship between endometrial concentrations of estrogen and progesterone receptors throughout the menstrual cycle in women with unexplained infertility.Material and methods:In forty four infertile women with unexplained infertility, biopsy of the endometrium was performed during simultaneous laparoscopy and hysteroscopy. Material was prepared for immunohistochemical staining. Forty four endometrial samples obtained from women with normal menstrual cycles were divided into four categories: early proliferative, late proliferative, early secretory and late secretory. Immunohistochemical localization of estrogen receptors (ER) and progesterone receptors (PR) was scored according to intensity of staining and proportion of cells specifically stained in glandular epithelium and stroma and results were analyzed.Conclusion:The early secretory phase appeared to be period of transition from the strong and ubiquitous staining for receptor characteristic of proliferative phase of endometrium to the weak, focal pattern of estrogen receptors. Progesterone receptors in early secretory phase were of strong staining and sufficient number of stained cells.

Cathepsin D as an indicator of clinical outcome in early breast carcinoma during the first 3 years of follow-up

The aim of this study was to evaluate clinical usefulness of cathepsin D status in early breast cancer during the first 3 years of follow-up. The study included 226 patients with histologically verified, primary operable invasive early breast carcinomas. Concentrations of estrogen receptor (ER) and progesterone receptor (PR) in breast tumor cytosols were measured by use of the classical biochemical method. The concentration of three cathepsin D forms (52-, 48- and 34-kDa proteins) was determined by a radioimmunoassay On the basis of differences in cathepsin D levels either within an ER(-)/PR(-) phenotype or between this and either ER(+)/PR(+) or ER(+)/PR(-) phenotypes, a concentration of 39 pmol/mg was determined as the cutoff value for distinguishing estrogen-regulated cathepsin D expression. Estrogen-regulated cathepsin D expression was recognized as a high-risk biomarker for low-risk (histological grade I) breast cancer patients and as a low-risk biomarker for high-risk patients (pN(+) pT2,3). Determination of cathepsin D status in breast cancer might identify patients at different risk for relapse and might facilitate the selection of more or less aggressive adjuvant therapy for early breast cancer patients during the first 3 years of follow-up.

Localization patterns of steroid and luteinizing hormone receptors in the corpus luteum of Nelore (Bos taurus indicus) cows throughout the estrous cycle

The aim of the present study was to detect progesterone receptors (A and B isoforms), α and β estrogen receptors, luteinizing hormone receptors and aromatase cytochrome P450 enzymes in the corpus luteum of Nelore (Bos taurus indicus) cows using immunohistochemistry. The estrous cycles of 16 Nelore cows were synchronized, and luteal samples were collected via an incision into the vaginal vault. Samples were collected during specific days of the estrous cycle (days 6, 10, 15 and 18) and 24h after circulating progesterone dropped, after luteolysis had occurred. After each biopsy was taken, all animals were resynchronized so that each biopsy was performed during a different estrous cycle. Our results showed that the concentration of studied proteins vary throughout the bovine estrous cycle. The highest concentration of α and β estrogen receptors and the highest concentration of plasma progesterone were both observed on days 10 and 15 of the estrous cycle. The highest concentration of progesterone receptors was observed on days 6 and 10 of the estrous cycle, and the most intense immunostaining for cytochrome P450 aromatase enzymes was observed on day 10 of the estrous cycle. The highest score of cells with plasma membrane immunostaining for LH receptors was observed on day 15 of the estrous cycle. In conclusion, this study demonstrates the varying concentrations of specific proteins within the corpus luteum of Nelore cows during the estrous cycle. This finding suggests that these receptors and enzymes, and their interactions, are important in regulating luteal viability.