Progesterone Receptor In Patients Research Articles

Epigenetics, endometriosis and sex steroid receptors: An update on the epigenetic regulatory mechanisms of estrogen and progesterone receptors in patients with endometriosis.

Endometriosis is a benign gynecological disease affecting ∼10% of reproductive-aged women and is defined as the presence of endometrial glands and stroma outside the uterine cavity. Endometriosis can cause a variety of health problems, from pelvic discomfort to catamenial pneumothorax, but it's mainly linked with severe and chronic pelvic pain, dysmenorrhea, and deep dyspareunia, as well as reproductive issues. The pathogenesis of endometriosis involves an endocrine dysfunction, with estrogen dependency and progesterone resistance, and inflammatory mechanism activation, together with impaired cell proliferation and neuroangiogenesis. The present chapter aims to discuss the main epigenetic mechanisms related to estrogen receptors (ERs) and progesterone receptors (PRs) in patients with endometriosis. There are numerous epigenetic mechanisms participating in endometriosis, regulating the expression of the genes encoding these receptors both indirectly, through the regulation of transcription factors, and directly, through DNA methylation, histone modifications, micro RNAs and long noncoding RNAs. This represents an open field of investigation, which may lead to important clinical implications such as the development of epigenetic drugs for the treatment of endometriosis and the identification of specific and early biomarkers for the disease.

Frequency of HER-2 NEU Receptor Positivity and its Relationship with Estrogen Progesterone Receptors in Patients of Breast CA

Background: Carcinoma breast is the commonest malignancy of females all over the world and second leading cause of death due to cancer among females. In Pakistan it is more common at a young age contrary to the West where it is more common in old age (after 60 years). The objectives of this cross sectional study were to determine the frequency of HER-2/neu receptor over-expression and its association with some of the features of breast cancer like patient age, ER/PR status, tumour size, histological grade and axillary lymph node involvement. Methods: This study was conducted at Surgery ward unit 2, Fatima Memorial Hospital, Lahore, from June 2015 December 2015. Study included all patients with breast cancer admitted in Surgery unit 2 of FMH, Lahore for Modified Radical Mastectomy (MRM). The resected specimens were sent to histopathologist for immunohistochemical (IHC) studies (HER-2/neu receptor and ER/PR) and detailed histopathological analysis including tumour subtype, size, histological grade and involvement of axillary lymph nodes. Patients refusing HER-2/neu receptor immunohistochemistry were excluded from the study. Name, age, sex, other relevant data, detailed history and clinical examination findings and results of investigation were recorded. Data was analyzed with SPSS version 10. Results: This study included 50 patients of breast cancer having modified radical mastectomy (MRM). Age distribution ranged from 45-61 years with a Mean±SD of age 52.2±4.3 years. 30 out of 50 patients (62.5%) were >52 years, while 20 patients out of 50 (40%) were ≤40 years of age. The HER-2/neu receptor status was found positive in 30 patients (60%) and negative in 20 patients (40%) of the total cases While, it was significantly associated with tumour size (p<0.05) and negative ER/PR status (p<0.05). Conclusion: Due to high prognostic significance and frequency in Pakistani females with breast cancer, HER-2/neu receptor should be checked in all patients with breast cancer so that the positive cases should have herceptin therapy and benefit from anthracycline based chemotherapeutic agents which can improve survival in these patients. Keywords: Breast carcinoma, HER-2/neu, ER/PR

A DESCRIPTIVE OBSERVATIONAL STUDY OF DIFFERENCE OF ESTROGEN & PROGESTERONE RECEPTOR STATUS BEFORE AND AFTER NEOADJUVANT CHEMOTHERAPY IN BREAST CANCER

Background: Neoadjuvant chemotherapy (NACT) forms the initial modality of treatment for primarily inoperable locally advanced breast cancer (LABC). A change in hormone receptor status after NACT has important therapeutic and prognostic consequences. The primary objective of this study is to compare Hormone Receptor status before and after neoadjuvant chemotherapy (discordance). The secondary objective is to study correlation between tumour response and hormone receptor expression. Method: This is a descriptive study of 80 LABC patients who received NACT. All patients who underwent core biopsy and ER/PR assessment before and after NACT were included in this study. Data was collected prospectively from each patient in a structured proforma Results and conclusion: The hormone receptor discordance rate & response to NACT was assessed. ER discordance is 16.4%. in 07 patients estrogen receptor(ER) change positive to negative and in 04patients estrogen receptor change negative to positive. PR discordance is 22.4%. In 12 patients Progesterone receptor (PR) change positive to negative and in 03patients progesterone receptor change negative to positive.

Investigating the Factors Associated with the Level of Expression of Estrogen and Progesterone Receptors in Patients Suffering from Colorectal Cancer.

Background The present study was performed to investigate the factors related to the expression level of estrogen and progesterone receptor in patients with colorectal cancer. Material and Methods. This crosssectional study was performed on 54 patients suffering from colorectal cancer referring to Imam Reza Hospital in Birjand during 2018-2019. After the biopsy performed during surgery, the specimen was sent for immunohistochemistry, and the status of receptors was determined. Eventually, the data were analyzed by SPSS 22. Results Out of the 54 patients studied, 64.8% were male. The mean age of the patients was 62.28 ± 14.03 years. The level of expression of beta-estrogen receptors and progesterone receptors had a significant relationship with age, consuming drugs of abuse, and familial history (P = 0.001). Also, the level of expression of estrogen and progesterone receptors of patients with a more advanced stage of cancer was significantly lower (P = 0.001). Conclusion The extent of expression of estrogen and progesterone receptors affects the progression and prognosis of disease. Thus, through hormone therapy, a step can be taken to reduce the progression and even to treat colorectal cancer.

Investigation of the change in the biological structure of the tumor in metastatic breast cancer

Objective: When metastasis develops in some breast cancer patients, hormone receptors (HR) and Human Epidermal Growth Factor-2 (Her-2) status can change and the tumor alters its character. We tried to determine the rate of these changes in tumor biology in 110 patients that we followed in our clinic and performed the change of the biopsy from the metastatic site (re-bx). We aimed to determine the biological changes of tumors and, contribute to the literature by examining the relationship of these changes with the adjuvant endocrine treatments (ET) or chemotherapy type (CT).
 Material and Methods: We included 110 metastatic breast cancer patients in our study. These patients had previously completed their local treatments followed by CT, and those with positive HR completed ET. After the first metastasis developed in the patients, we performed metastasectomy or biopsy from the metastatic site.
 Results: The median ki-67 value was 25% at the time of primary diagnosis and 30% in re-bx. 20.9% of patients estrogen receptor (ER), 31.8% of patients progesterone receptor (PR) and 26.3% of patients Her-2 changed when metastasis developed.
 Conclusions: We found that the metastatic tumor has more aggressive properties than the primary tumor. Adjuvant chemotherapy and endocrine treatments or the location of metastasis did not make a significant difference in tumor biology.

Characterization of Progesterone Receptor Expression in Intracranial Meningiomas of Patients Treated in a High-Complexity Hospital in Bogota, Colombia.

BackgroundMeningiomas are the single most common brain tumor. The incidence of these tumors increases with age; different studies have shown that meningiomas usually appear after the age of 50. These tumors are more common in women than in men, and women are twice as likely to suffer from the condition. Surgery is the primary form of treatment, which can be curative with complete resection. If the tumor is unresectable or other treatments such as surgery and radiotherapy have failed, hormonal therapy or chemotherapy may be considered. There is limited information about the clinical, demographic, and histopathological characteristics of these tumors in the population of Bogotá, Colombia.ObjectiveTo evaluate the expression of progesterone receptors in patients over 18 years old who have been diagnosed with meningiomas in a high-complexity hospital in Bogota, Colombia, and to describe the demographic and histopathological characteristics of these patients.MethodsThis is a descriptive and retrospective case series. Patients with meningioma who underwent surgical resection at a high-complexity hospital in Bogota, Colombia, from 2016 to 2019 were retrospectively identified and studied. Demographic variables, such as age and gender, were extracted from the clinical chart. Indirect immunoperoxidase staining was carried out for the progesterone receptor (PR) and Ki67. PR is analyzed as positive and negative, and the Ki67 proliferation index was determined.ResultsThirty-two meningiomas from patients who underwent surgery were available for analysis. Twenty-five (78.1%) were positive for PR, 71.8% were females, and 93% were World Health Organization (WHO) grade I. Meningothelial (28%), fibrous (25%), and transitional (25%) meningiomas were the most frequent subtypes, correspondingly. The Ki67 mean value was 1.14 (0.11-10.71).ConclusionOur case series showed a greater frequency of meningiomas in women, with a high PR expression and a low Ki67 proliferation rate. These data correlate with literature worldwide.

Progesterone and estradiol receptors and Ki-67 in the superficial and deep infiltrating endometriosis

ABSTRACT Introduction: Endometriosis is a hormone-dependent disease characterized by ectopic presence of endometrial tissue responsive to ovarian steroids. Estrogen and progesterone are the main regulators of endometrial tissue, and the expression of receptors of these hormones in the ectopic tissue seems to be related to the pathophysiology of the disease. Ki-67 is a marker of tissue proliferation and an important marker of epithelial kinetics. Endometriosis can be classified as superficial, in the peritoneum, and deep, when it extends into ligaments and other organs. Objective: Our objective was to analyze the expression of estrogen and progesterone receptors and Ki-67, through immunohistochemistry, in different sites of endometriosis tissues (superficial peritoneal/ovarian endometriosis and deep infiltrating endometriosis). Casuistic and methods: We studied nine patients; five with superficial and four with deep endometriosis. Statistical correlation was performed with the Shapiro-Wilk test (significance level of 5%) and linear correlation analysis using Spearman’s non-parametric test (significance of 1%). There was a correlation of Spearman between the estrogen receptor variable and Ki-67 in patients with superficial endometriosis. There was also a correlation between the variables estrogen receptor and progesterone receptor in patients with deep endometriosis. Results: Contrary to what was found for superficial endometriosis, there is linear increase of the variables, with a strong and positive correlation coefficient. This demonstrates that the variation of estrogen receptors can be explained in 99.1% by the same variation of progesterone receptors in deep endometriosis. Conclusion: It is possible to infer that other factors are involved in the response to hormonal variations for superficial and deep endometriosis.

Пролиферативные заболевания матки: клинико-анамнестические, иммунологические и молекулярно-генетические аспекты

Objective. To perform comparative analysis of clinical data, serum levels of acute-phase proteins, cytokines, steroid hormones, and expression of genes encoding sex hormone receptors in tissues of patients with proliferative diseases of the uterus. Patients and methods. We analyzed clinical data of 349 patients with various proliferative diseases of the uterus. We also evaluated their serum levels of α2-macroglobulin, pregnancy-associated α2-glycoprotein, their immunocomplexes with IgG, lactoferrin, VEGF, IL-6, TNFa, IL-8, and sex hormones. Uterine tissue samples were tested for the expression of genes encoding estrogen receptors α and β (ЕRα, ЕRβ) and progesterone receptors (PGR). Data analysis was performed using the statistical packages of SAS 9.4, STATISTICA12, and IBM-SPSS Statistics 22. Results. The changes in the level of acute-phase proteins indicated inflammation. In isolated uterine fibroids, expression of genes encoding progesterone receptors prevailed, whereas in isolated adenomyosis, expression of genes encoding estrogen receptors prevailed. Patients with both uterine fibroids and adenomyosis demonstrated similar levels of expression of genes encoding sex steroid hormone receptors. Tissues of uterine leiomyosarcoma were characterized by downregulated expression of genes encoding sex steroid hormone receptors. Conclusion. Upregulation of genes encoding progesterone receptors in isolated uterine fibroids confirms that therapy with progesterone receptor blockers is appropriate in this case. The predominance of expression of genes encoding estrogen receptors in isolated adenomyosis indicates local hyperestrogenism, justifying the use of progestogens and antiestrogens. Equal expression of genes encoding estrogen and progesterone receptors in patients with combined disease, as wells as high frequency of inflammatory changes in tissues and increased serum levels of inflammatory markers, proves the need for antiinflammatory therapy. Key words: adenomyosis, inflammation, steroid receptor genes, leiomyosarcoma, uterine fibroids, gene expression

The prognostic role of progesterone receptor in patients with rapidly proliferating, hormone receptor-positive early breast cancer.

545 Background: The prognostic role of progesterone receptor (PgR) in highly proliferating early breast cancer (BC) is not well established. We retrospectively explored this biomarker in a cohort of patients with highly proliferating tumors enrolled in a phase III trial of adjuvant therapy. Methods: 1066 patients with N- or 1-3 N+ BC were randomized to receive: epirubicin followed by CMF, CMF followed by epirubicin, or CMF alone. Rapidly proliferating tumors were defined by thymidine labeling index (TLI) > 3% or histological grade 3 or S-phase > 10% or Ki67 > 20%. We analyze the subgroup of 466 patients with hormone receptor (HR)-positive tumors treated with sequential epirubicin/CMF regimens followed by tamoxifen and for whom immunohistochemical assessments of estrogen receptor (ER), PgR, HER2 and Ki67 were available. Disease-free (DFS) and overall survival (OS) curves were built with the Kaplan–Meier estimator and compared by logrank test and Cox regression models. Results: PgR expression was significantly associated with ER expression, HER2 status, age and menopausal status, but not with Ki67, tumor size and nodal status. PgR cutoff values of 10% and 20% were chosen based on a Receiver Operating Characteristics analysis and the literature data. DFS and OS figures at 5 and 10 years, as well as the relative hazard ratios, according to the different PgR cutoff values, are reported in the table. Conclusions: Our results confirm the prognostic relevance of PgR expression in a cohort of patients with highly proliferating, HR-positive early BC treated with adjuvant chemotherapy and endocrine therapy. [Table: see text]

Association of tumor size and estrogen Progesterone receptors in patients with carcinoma breast

Association of tumor size and estrogen Progesterone receptors in patients with carcinoma breast

Abstract PD8-07: Identifying steroid hormone receptor gene mutations in patients with newly diagnosed estrogen receptor positive metastatic breast cancer

Abstract Background: Resistance to endocrine therapy remains a challenge for patients with metastatic hormone receptor positive breast cancer. Mutations in the gene encoding estrogen receptor alpha (ESR1) have been identified in patients with endocrine resistance and correlates with reduced survival. The occurrence of mutations in the gene for progesterone receptor (PGR), another important biomarker in breast cancer, has not been reported. Objective: Determine the frequency of mutations in ESR1 and PGR in patients with newly diagnosed metastatic ER+ breast cancer treated with adjuvant endocrine therapy at our institution, and identify whether these mutations are associated with worse patient survival. Methods: This is an IRB-approved, HIPAA-compliant retrospective study of patients with ER+ metastatic breast cancer identified from our comprehensive cancer center registry. Eligible patients must have received at least 6 months of adjuvant endocrine therapy with biopsy-proven diagnosis of metastatic or locally recurrent disease. Next-generation sequencing of the coding regions of ESR1 and PGR was performed on extracted tumor genomic DNA. Analysis was limited to protein coding mutations. Clinicopathologic data was collected and correlated with the genomic information for each patient. Associations between mutation status and clinicopathologic factors were analyzed using Fisher's exact test. Kaplan-Meier method with log-rank test was used to analyze overall survival (OS) from time of metastatic diagnosis. Results: The study included 35 women (35-88 yr old). Metastatic sites included bone (N=13), brain (N=6), chest wall (N=2), liver (N=4), lung/pleura (N=4), and lymph nodes (N=6). PGR mutations were identified in 66% of patients (23/35; 95%CI 48-81%), and were more common than ESR1 mutations (10/35; 29%; 95%CI 15-46%). Mutations in both PGR and ESR1 were identified in 26% (9/35), and neither mutation was identified in 31% (11/35). Neither mutation was associated with prior adjuvant aromatase inhibitor or tamoxifen therapy. There was no significant association between ESR1 or PGR mutations and metastatic site, although 75% (3/4) of patients with liver metastases had an ESR1 mutation compared to 23% (7/31) without liver metastases (p=0.061). The differences in median OS between ESR1 wildtype vs mutant (1.6 mo vs 1.0 mo, p=0.14) and PGR wildtype vs mutant (2.6 mo vs 1.3 mo, p=0.56) were not significant. However, patients with both mutations may have worse median OS compared patients with neither or only one mutation (1.0 mo vs 1.6 mo vs 4.0 mo, p = 0.073). Conclusions: The overall survival of metastatic ER+ breast cancer patients with ESR1 or PGR mutations were not statistically significant compared with those without mutations. Despite the small sample size, there is a trend that patients with mutations in both genes may have worse survival. To the best of our knowledge, the PGR mutation rate in metastatic breast cancer has not previously been reported. Interestingly in our data set, PGR mutations were identified more commonly than mutations in ESR1. The significance of PGR mutations is not known, nor whether this could be a future indicator of treatment resistance or a target for therapy. Citation Format: Fowler AM, Rassman S, DeGrave M, Ong I, Powers GL, Salem K, Kumar M, Woo K, Mahajan AM. Identifying steroid hormone receptor gene mutations in patients with newly diagnosed estrogen receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD8-07.

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.

Immunohistochemical Expression of Estrogen Receptor-α and Progesterone Receptor in Patients with Papillary Thyroid Cancer

Background: Papillary thyroid cancer (PTC) prevalence is nearly 3 times higher in females than in males. This gender difference suggests that growth and progression of PTC might be influenced by female sex hormones. Objectives: To analyze the expression of both estrogen receptor (ER)-α and progesterone receptor (PR) by immunohistochemistry in 203 PTC patients. Methods: ER-α and PR expression was evaluated in paraffin-embedded tumor tissue samples of 45 males and 158 females followed up for 7.2 ± 3.7 years. Results: ER-α was expressed in 52 (25.6%) patients (41 females and 11 males) and PR in 94 (46.3%) patients (75 females and 19 males). ER-α and PR were coexpressed in 31 (15.3%) patients (27 females and 4 males). ER-α expression correlated significantly with tumor size in the whole sample (ER-α positive 22.8 ± 11.8 mm vs. ER-α negative 15.1 ± 12.4 mm; p = 0.02) and in the subgroup of women (ER-α positive 18.8 ± 12.8 mm vs. ER-α negative 14.9 ± 12.3 mm; p = 0.048). In addition, ER-α expression significantly correlated with remission of the disease. In fact, of the 192 patients followed up, 50/153 (32.7%) disease-free patients were ER-α positive, in contrast to only 3/39 (7.7%) with evidence of disease persistence/recurrence (χ² = 8.5, p = 0.0036). PR expression was not associated with any of the parameters analyzed. Conclusions: The present study confirmed recent data indicating that ER-α and PR expression is a common finding in thyroid tumor tissue. However, in contrast to previous reports, we observed an association between ER-α expression and a more favorable outcome in PTC patients.

Abstract P6-08-02: The body mass index interacts with the prognostic effect of the progesterone receptor in patients with a luminal HER2 negative breast cancer

Abstract Background Obesity (body mass index (BMI) &amp;gt;30) increases breast cancer (BC) risk and promotes BC metastases probably through high estrogen levels. A high BMI as a risk and prognostic factor is consistently reported in postmenopausal women. Obese women develop particularly hormone receptor positive, HER2 negative BC. In this study, we investigate the influence of BMI on the prognostic effect of the progesterone receptor (PR) in postmenopausal patients with estrogen receptor (ER) positive, HER2 negative BC. Patients and methods Women over 50 years of age diagnosed with primary operable BC between 2000 and 2012 at University Hospitals Leuven were retrieved from the database. Patients were subdivided into normal weight (&amp;lt;25 kg/m2), overweight (&amp;gt;25 and ≤30) and obese (&amp;gt;30). We investigated for each BMI category the distant metastasis free interval (DMFI) and BC specific survival (BCSS) by PR status. Apart from the total cohort, subgroup analysis was performed for luminal A (grade 1-2) and luminal B HER2 negative BC (grade 3). We used Fine and Gray’s competing risk regression for the analyses. Covariates were age at diagnosis, tumor size, lymph node status, and therapy. Results In total, 3227 patients were analyzed for DMFI. For BCSS, 3192 patients were analyzed as patients with unknown cause of death were excluded from the analysis. 2395 of all patients had luminal A and 832 had luminal B HER2 negative BC (Table 1). Median time of follow-up was 6.5 years. Table 1: Percentage of luminal A and luminal B patients per BMI category BMI&amp;lt;25BMI &amp;gt;25 and ≤30BMI &amp;gt;30Luminal A1105 (76%)820 (75%)470 (70%)Luminal B355 (24%)278 (25%)199 (30%)BMI: body mass index BMI interacts with the prognostic effect of PR for DMFI and BCSS in luminal HER2 negative BCs. Only patients with BMI &amp;lt;25 had a reduction in the risk of distant metastasis and BC-related death if the tumor was PR positive as compared to patients with PR negative BC. This was observed in the total cohort and only seen in the luminal B subgroup (table 2). A similar effect was observed in obese patients but this did not reach statistical significance, and was mainly present during the first 5 years following diagnosis. For the overweight patients, no difference in DMFI and BCSS was observed by PR status. Table 2: Multivariate analysis for DMFI and BCSS for PR positive versus PR negative in the 3 BMI categories in the total and the luminal B cohort. DMFI (HR, 95% CI)BCSS (HR, 95% CI)Total cohort BMI &amp;lt;250.25, 0.16 to 0.400.22, 0.12 to 0.40BMI &amp;gt;25 and ≤301.24, 0.59 to 2.600.95, 0.40 to 2.25BMI &amp;gt;300.70, 0.33 to 1.490.53, 0.21 to 1.33luminal B BMI &amp;lt;250.19, 0.11 to 0.330.14, 0.06 to 0.31BMI &amp;gt;25 and ≤301.23, 0.44 to 3.481.02, 0.36 to 2.85BMI &amp;gt;300.82, 0.31 to 2.200.61, 0.18 to 2.00BCSS: breast cancer specific survival, BMI: body mass index, CI: confidence interval, DMFI: distant metastasis free interval, HR: hazard ratio Conclusion Normal weight patients have a reduced risk of developing distant metastases and of BC-related death if the tumor is PR positive compared to PR negative BC. No difference between PR positive and PR negative cases was observed in overweight BC patients. This BMI-dependent prognostic effect of PR was limited to luminal B BC patients. Citation Format: Kathleen Van Asten, Anneleen Lintermans, Annouschka Laenen, Chantal Remmerie, An Poppe, Giuseppe Floris, Hans Wildiers, Marie-Rose Christiaens, Patrick Neven. The body mass index interacts with the prognostic effect of the progesterone receptor in patients with a luminal HER2 negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-02.

Biological profile of oestrogen receptor alpha positive (ERalpha+) primary breast cancers in the elderly and their response to primary endocrine therapy

e20622 Background: Aromatase inhibitors (AIs) have been shown to be superior to tamoxifen in several settings. However, it is unclear whether this superiority extends to its use as primary endocrine therapy in elderly patients with early operable primary breast cancer. Biological characteristics of the tumours may aid in selecting the most suitable agent. Methods: Primary endocrine therapy with one of the AIs (anastrozole) in 64 women &gt;70 years with ERα+ breast cancer was compared to that in 84 treated with tamoxifen during the same period. Their selection was entirely based on contraindications e.g. thromboembolic risks. Needle core biopsies were assessed, by immunohistochemistry, for expression of biomarkers as described below. Results: There was no significant difference between the two groups (anastrozole vs tamoxifen) in terms of response at 6 months (clinical benefit (objective response + stable disease) rates = 97 vs 100%, p=0.099) or progression free survival (median = 16.5 vs 22.5 months, p=0.376). There were no withdrawals due to side effects from anastrozole, compared to four with tamoxifen. For all patients progesterone receptor (PgR), ERβ2, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and Ki-67 were over-expressed in 48%, 99%, 8%, 4% and 64% respectively. HER2 (18 vs 21 months, p=0.003) and Ki-67 (17.5 vs 23 months, p=0.042) over-expression were significantly associated with shorter progression free survival. Conclusions: These results thus far show that primary endocrine therapy with anastrozole in elderly patients with early operable ERα+ breast cancer is similar to tamoxifen in terms of efficacy, but may be better tolerated. In this population, ERα+ breast cancer also appears to have a less aggressive biological profile favouring better hormone sensitivity. [Table: see text]

Solving the dilemma of the immunohistochemical and other methods used for scoring estrogen receptor and progesterone receptor in patients with invasive breast carcinoma

The authors attempted to resolve the dilemma posed by the lack of unanimity concerning the optimal immunohistochemical (IHC) method for determining and scoring estrogen receptor (ER) and progesterone receptor (PR). Sections for IHC were prepared from paraffin embedded tumor samples from 402 patients with lymph node positive breast carcinoma who had biochemical receptor values (obtained with the dextran-coated charcoal [DCC] method) and who were enrolled in a prospective, randomized trial (National Surgical Adjuvant Breast and Bowel Project protocol B-09). IHC receptors were scored independently by two observers according to percent, intensity, and any-or-none algorithms. Results from these evaluations and from two computer-assisted evaluations, DCC, and common pathologic characteristics were analyzed for optimum splits for positive reactions in univariate and multivariate analyses using a tree-structured model. Concordance, sensitivity, and specificity were determined between the DCC method and all other methods. Interobserver agreement and concordance between the DCC method and the other methods and among the methods were high. Univariate analyses revealed that a positive ER score obtained with all methods was related significantly to overall survival (OS) at 5 years and at 10 years. Results related to PR scores and disease-free survival and recurrence-free survival were less consistent. In multivariate analysis, it also was found that all methods for scoring ER predicted a better prognosis for OS in patients with an unfavorable lymph node status at 5 years and 10 years. Patients in a favorable lymph node status group were discriminated further by nuclear grade. All IHC methods for scoring ER appeared valid as prognostic indicators of OS in patients with positive lymph nodes. The any-or-none IHC method, by virtue of its simplicity, represents an appropriate choice for practical use.

Progesterone receptor in patients with hepatolithiasis.

Altered gallbladder motility by progesterone has been recognized as an important factor in the development of gallstones. There are two types of hepatolithiasis, that occurs de novo in the intrahepatic ducts with an intact gallbladder (primary hepatolithiasis) and that which originates in the gallbladder and the stones migrate into the intrahepatic duct (secondary hepatolithiasis). This study was designed to evaluate the possible role of the progesterone receptor of gallbladder in the pathogenesis of hepatolithiasis. Eighty-four patients with hepatolithiasis (34 patients had primary hepatolithiasis and the other 50 patients secondary hepatolithiasis) were included. Paraffin-embedded specimens of gallbladder were processed to have an immunohistochemical staining for progesterone receptor. Positivity for progesterone receptor of gallbladder specimens was noted in eight patients (23.5%) with primary hepatolithiasis and in 23 patients (46%) with secondary hepatolithiasis. There is significant difference (P = 0.031) in positive rate for progesterone receptor between the primary hepatolithiasis and secondary hepatolithiasis groups. In conclusion, many more patients (46%) with secondary hepatolithiasis show positivity for progesterone receptor of gallbladder specimens than patients with primary hepatolithiasis (23.5%) (P = 0.031). This phenomenon is intriguing and should be of further evaluation and elucidated.

Estrogen and progesterone receptors in gynecomastia.

The etiology of gynecomastia is unknown. There seems to be no increased incidence of malignancies in patients with idiopathic gynecomastia; however, patients with Klinefelter syndrome exhibit an increased incidence of malignancy. The authors reviewed the results of 34 patients with gynecomastia diagnosed in adolescence who, following initial evaluation, had a mastectomy. The estrogen and progesterone receptors were analyzed in these patients. Three of the patients were diagnosed with Klinefelter syndrome. These three patients exhibited elevated amounts of estrogen and progesterone receptors. None of the patients who were not diagnosed with this syndrome demonstrated significant elevation of their estrogen or progesterone receptors. The presence of elevated estrogen and progesterone receptors in patients with Klinefelter syndrome provides a potential mechanism by which these patients may develop breast neoplasms. The absence of elevated estrogen and progesterone receptors in patients with idiopathic gynecomastia may serve to clarify why these patients' disease rarely degenerates into malignancy.

Prognostic role of oestrogen and progesterone receptors in patients with breast cancer: relation to age and lymph node status.

To consider the prognostic role of oestrogen receptor and progesterone receptor status in relation to the age at surgery, length of follow up and lymph node status. The study population comprised 977 patients with histologically confirmed breast carcinoma, with a median follow up of nine years. The actuarial life table method was used to test for survival differences. The Cox proportional hazard model was used to test for interaction effects between each hormone receptor and age, lymph node status and length of follow up. As the analysis involved multiple subgroups, significance was set at the 1% level (p < 0.01). When the patients were subdivided into groups according to lymph node status and age, progesterone and oestrogen receptor status predicted prognosis in middle aged (46-60 years) patients with lymph node positive breast cancer. Their prognostic effect in this subgroup, however, was restricted to the first five years after surgery. Progesterone receptor status was the strongest predictor of outcome. The prognostic power of oestrogen and progesterone receptor status varies depending on age, lymph node status and length of follow up after surgery.

Estrogen and progesterone receptors in human meningiomas: Biochemical and immunocytochemical evaluation

BACKGROUND The observation that human meningiomas are rich in steroid hormone receptors has led to the hypothesis that their growth may be hormonally dependent. This study aims to correlate the biochemical expression of estrogen (ER) and progesterone receptors (PgR) with their nuclear immunoreactivity in a large series of meningiomas. METHODS The occurrence of ER and PgR in patients with primary untreated meningiomas was studied with a dextran-coated charcoal method (DCC) and the results were compared with those of an immunocytochemical assay (ICA). Progesterone and estrogen receptor determinations were performed on 103 and 99 meningiomas respectively using the DCC assay. Forty-six and 44 of these samples were immunocytochemically evaluated for the presence of PgR and ER respectively. RESULTS Of the 46 samples evaluated by both the methods, 89% were found PgR positive by DCC and 70% by ICA. The overall concordance between PgR-DCC and PgR-ICA was 80%. Whereas low concentrations of ER were found in 8 44 samples (18%) assayed by DCC, specific staining was never observed in any of the samples tested by ICA. CONCLUSIONS Our findings confirm that the majority of meningiomas are devoid of ER and that the biochemical evidence of PgR correlates well with the nuclear localization of progesterone receptors determined by immunocytochemistry.