Significance Of Estrogen Receptor Research Articles

Molecular and Cellular Expressions in Breast Cancer Responsible for Drug Resistance

Breast cancer continues to be a prevalent and highly lethal cancer affecting women globally. Despite significant advancements in early detection and the development of specific therapeutic approaches, the issue of medication resistance remains a prominent challenge in managing this intricate ailment. The study offers a comprehensive analysis of the mechanisms behind the development of treatment resistance in breast cancer cells. The objective of this study is to provide a comprehensive understanding of the molecular and cellular mechanisms behind the occurrence of therapeutic ineffectiveness. This study elucidates several molecular subtypes of breast cancer and their pharmacological responses. The significance of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in the development of treatment resistance is emphasized. Additional research on the intricacies of innate and acquired drug resistance mechanisms, including genetic modifications, tumor heterogeneity, and the presence of cancer stem cells, has shed light on the multifaceted nature of drug resistance and its dynamic evolution throughout treatment. Furthermore, this study provides a comprehensive analysis of the impact of microenvironmental variables, including hypoxia, immune evasion, and tumor-stroma connections, on the development of drug resistance. The investigation of the interplay between tumor suppressors and oncogenes in the emergence of drug resistance is now underway, yielding valuable insights into prospective targets for therapeutic intervention. Additionally, this study examines the limitations associated with conventional chemotherapy, endocrine therapies, and targeted medicines, while elucidating the mechanisms underlying treatment resistance and proposing potential strategies to overcome it. Emerging therapies like immunotherapies, epigenetic modulators, and new drug delivery methods are looked at to see if they have the potential to get around mechanisms of resistance and improve patient outcomes. This review aims to give clinicians, researchers, and other healthcare workers a full picture of breast cancer’s complex drug resistance mechanisms. By figuring out the molecular complexities and signaling pathways that lead to treatment resistance, we aim to speed up the development of new therapeutic approaches and personalized interventions. This will bring us closer to the long-awaited goal of beating drug resistance and making breast cancer a manageable, treatable condition.

Expression and significance of estrogen receptor and progesterone receptor in endometrial tissue of patients with intrauterine adhesions.

Our study aims to analyze the expression and significance of estrogen receptor (ER) and progesterone receptor (PR) in endometrial tissues of patients with intrauterine adhesion (IUA). Fifty-four patients with IUAs examined in our hospital from January 2017 to January 2019 were selected as the research object (observation group), 54 healthy women who had physical examinations during the same period were selected as the control group, and the immunohistochemical EnVision was used. Two-step and real-time fluorescent quantitative PCR methods were used to detect the expression levels of ER and PR in the endometrial tissues of the two groups of subjects. The immunohistochemical test results showed that ER's expression level in the observation group was significantly higher than that in the control group, and the difference between the two groups was statistically significant (P<0.05). The difference in PR expression levels between the two groups was insignificant (P<0.05). Real-time fluorescent quantitative PCR results showed ER and PR's expression levels in the observation group were significantly higher than those in the control group, and the difference between the two groups was statistically significant (P<0.05). After IUA can detect ER and PR expression, we can formulate a personalized hormone treatment plan to improve the clinical treatment effect.

The significance of estrogen receptors in acromegaly: Are they useful as predictors of prognosis and therapy regimen?

ObjectiveIn this study, we considered to assess the presence of estrogen receptors (ER) and the expression of estrogen receptor genes (ESR) in the surgical tissue samples of acromegaly patients and the control group patients with nonfunctioning adenoma and their association with disease activity. We also aimed to determine the significance of ER positivity in acromegaly patients and to find out whether it carries a potential to be used as a predictor of prognosis and therapy regimen in the future. DesignThis study was conducted on a total of 67 patients over 18 years of age. The study group consisted of 34 patients with acromegaly and 33 patients with nonfunctioning pituitary adenoma. The pre- and post-operative basal pituitary hormone levels and magnetic resonance images (MRI) of all patients, as well as their remission status of all acromegaly patients were evaluated. Immunohistochemical (IHC) staining procedures for ER-α were performed on surgical tissue samples. Real-time quantitative polymerase chain reaction (RT-qPCR) method was used to determine the levels of ESR1 and ESR2 gene expressions. ResultsWe found that IHC staining for ER-α was positive in 31.3% and 45.5% of the patients with acromegaly and nonfunctioning adenoma respectively. There was no statistically significant difference of ER-α positivity, ER-α immunoreactivity score and ESR1/ESR2 gene expression levels among the study groups (p > .05). Nevertheless, the expression of ESR1 gene was found to be 0.26 times more, and the ESR2 gene to be 0.11 times less in the acromegaly group compared to those of the nonfunctioning adenoma group. Additionally, we detected the positivity of ER-α only in acromegaly patients who were in remission. An inverse association was found between the pre-operative insulin-like growth factor-1 (IGF-1) levels and the expressions of ESR1/ESR2 gene in acromegaly patients. So these results indicated that the high ESR1 and ESR2 gene expressions in acromegaly patients are associated to the decrease of pre-operative IGF-1 values. Also an inverse association was found between the pre-operative adenoma volume and ESR1 Ct values, means that increase in ESR1 gene expression is associated to the decrease of adenoma volume. ConclusionsThe current results may suggest the use of these parameters as useful prognostic markers because all ER-positive acromegaly patients were in remission and the high ESR1 and ESR2 gene expressions in acromegaly patients is associated to the decrease of pre-operative IGF-1 values. Our results need to be supported by further studies.

Clinical significance of stromal ER and PR expression in periampullary adenocarcinoma

BackgroundTamoxifen treatment has previously been reported to confer life-prolonging effects in patients with advanced pancreatic cancer, and most evidently so in women. None of these trials did however include biomarkers, and the relevance of female hormone signaling in pancreatic or other periampullary adenocarcinoma remains largely unexplored. The aim of this study was to examine the extent and potential clinical significance of estrogen receptor-α (ER) and progesterone receptor (PR) expression in pancreatic and other periampullary cancers.MethodsER and PR expression was examined using immunohistochemistry on tissue microarrays with primary tumors from a retrospective consecutive cohort of 175 patients with resected periampullary adenocarcinoma, with long-term clinical follow-up. Non-parametric and Chi square tests were applied to examine the associations of stromal ER and PR expression with patient and tumor characteristics. Kaplan-Meier analysis and log rank test were applied to illustrate survival differences in relation to ER and PR expression. Cox regression proportional hazards models were applied to examine the associations between investigative factors and risk of death and recurrence, and to test for interactions between KRAS mutation status and hormone receptor expression in relation to survival.ResultsExpression of both ER and PR was more frequent in the tumor-associated stroma than in the epithelium. A significant prognostic interaction, independent of tumor morphology, was found between stromal PR expression and KRAS mutation status in relation to both overall and recurrence-free survival (pinteraction = 0.026 and pinteraction = 0.005), in particular in women (pinteraction = 0.002 and pinteraction = 0.005). Specifically, stromal PR expression was associated with a prolonged survival in patients with KRAS-mutated tumors, whereas the opposite was seen for KRAS wild-type tumors. The prognostic value of ER positivity was limited to the subgroup of women with tumors of pancreatic origin.ConclusionsThese results demonstrate that stromal PR rather than ER expression, together with KRAS mutation status, provides long-term prognostic information in patients with periampullary adenocarcinoma. Further study into the mechanistic basis for these observations may unveil important clues to the pathogenesis of these cancers and open up for the discovery of novel treatment options.

Abstract P5-11-07: The significance of androgen receptor co-expression in ER+ metastatic breast cancer patients treated with palbociclib

Abstract Background: The PALOMA-1 and PALOMA-3 studies demonstrated a significant progression-free survival (PFS) advantage for palbociclib, a CDK4/6 inhibitor, in combination with letrozole or fulvestrant in the first or second line setting compared to these therapies alone in estrogen receptor (ER)+, HER2-negative metastatic breast cancer (MBC). Recent studies have revealed preliminary efficacy signals for androgen receptor (AR) blockade in MBC, predominately in AR+, triple negative patients. We sought to further evaluate AR expression and its significance in ER+ MBC patients treated with palbociclib early in their metastatic treatment course. Methods: A retrospective review identified 22 patients treated with palbociclib for ER+, HER2- MBC after its FDA approval between January 1st, 2015 and October 1st, 2016 at our center with available pre-treatment tumor samples for analysis. Records were reviewed and clinical characteristics for each patient were analyzed. Archival tumor tissue was tested for AR, phosphorylated retinoblastoma (pRb), CDK6, p16, and CyclinE1 by immunohistochemistry assay for each patient. For AR, nuclear staining &amp;gt;0% was considered positive. For all other IHC studies, intensity of staining &amp;gt;2+ or staining in &amp;gt;10% of cells was considered positive. Results: The median age was 63.5 years (range 34-84); 23% were ≥ age 70. Our cohort was 35% African American, 60% Caucasian, and 5% Asian American. 64% of patients were post-menopausal and 59% had visceral metastases. 45% of patients were on their first line of treatment, 23% second line, and 32% third line. 68% of patients were on an aromatase inhibitor. Median follow up was 18.7 months (95% CI 13.9, 23.3 months). The AR was expressed in 59% of patients; 55% had expression &amp;gt;10% and 41% had expression &amp;gt;20%. AR+ patients were significantly more likely to experience event-free survival (EFS) (HR 0.26, p=0.01), with a median EFS of 18.8 months (AR- median EFS 5.4 months). AR expression was significantly associated with expression of pRb (100% of AR+ patients, p=0.02). CDK6, p16, and CyclinE1 expression were not associated with AR expression or EFS. Conclusions: Our data show preliminary evidence of the significance of ER and AR co-expression in ER+, HER2- MBC. ER+, AR+ patients have significantly improved EFS when treated with palbociclib and endocrine therapy as compared with AR-, ER+ patients. There is evidence that AR expression is associated with pRB expression, which may represent a mechanism by which cell cycle inhibition with palbociclib is particularly efficacious in these patients. AR expression rates in ER+, HER2- MBC are significant, and may provide rationale for combining CDK4/6 inhibitors with AR targeting as a subsequent line of targeted therapy in these patients before cytotoxic chemotherapy is initiated. Further studies based on these results are underway. Citation Format: Landry CA, Ru M, Jaffer S, Dimitrova M, Tiersten A. The significance of androgen receptor co-expression in ER+ metastatic breast cancer patients treated with palbociclib [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-11-07.

Expression and significance of estrogen receptor in bladder of experimental autoimmune encephalomyelitis mouse model

Objective To study the changes of estrogen receptor (ER) expression in neurogenic bladder caused by multiple sclerosis (MS) and its significance by establishing an experimental autoimmune encephalomyelitis (EAE) model in mice. Methods The EAE models were induced by an antigen emulsion mixture that was well mixed with mog35-55 and complete Freund’s adjuvant. Twenty female C57Bl/6 mice were randomly divided into experimental group and control group. The clinical symptoms of mice were observed and recorded after immunization. Twenty-third days after immunization, micturition frequency and mean void weight were observed within 4 h. The spinal cord as well as the bladder was collected and the bladder was weighed. The pathological changes were observed by hematoxylin-eosin (HE) staining and Luxol fast blue (LFB) staining. The expression of ER in bladder of EAE mice was detected by Western blotting. Results The clinical score of neurological function in EAE mice increased, and typical MS symptoms appeared. The weight of the control group and experimental group was (23.0±1.1) g and (16.5±1.5) g respectively. As compared with the control group, the weight of the mice in the model group was obviously reduced. The average number of 4H urination in model group (8.7±1.4) was significantly greter than in the control group (4.2±1.1, P=0.001). The urine volume in the model group [(0.22±0.11) mg] was significantly less than that in the control group [(0.34±0.07) mg, P=0.008]. In the model group, the bladder weight ratio [(0.26±0.09)‰] was significantly higher than that in the model group [(0.11±0.03)‰, P=0.001]. HE-LFB staining showed obvious inflammatory cell infiltration and demyelination in the spinal cord of EAE model mice, and Western blotting showed that the relative expression of ER in the bladder of model group (0.38±0.08) was significantly lower than that in the control group (0.71±0.19, P=0.001). Conclusion Mog35-55 can successfully induce the EAE mice model. The EAE mice model can well simulate the MS neurogenic bladder symptoms. ER and estrogen may be the important factors in bladder dysfunction caused by multiple sclerosis. Key words: Estrogen receptor; Experimental autoimmune encephalomyelitis; Neurogenic bladder

Abstract P5-05-06: Menopausal status: An important consideration in determining the biology and prognosis of estrogen receptor-positive and progesterone receptor-negative breast cancer

Abstract Background: Transcription of the progesterone receptor (PgR) gene is regulated by estrogen in the breast tissue. PgR loss is considered to be a result in the reduction of estrogen receptor (ER) activity, due to either low circulating estrogen in some older women or a high growth factor signaling. Among the ER-positive breast cancer patients, PR-negative cases frequently have a higher resistance to endocrine therapy, and have a poorer prognosis. Therefore, we examined the clinical significance of ER+/PgR- tumors in luminal/HER2 negative breast cancer and its relationship to menopausal status. Methods: The sample for this study came from 1791 consecutive patients with HER2 negative primary breast cancer from January 2002 to March 2013. The ER and PgR expressions were evaluated using immunohistochemistry (IHC). 1586cases had ER+/PgR+ tumor, 205cases had ER+/PgR- tumor. The items examined were nuclear grade, Ki-67 index value, TP53, tumor size and number of lymph node involvement. The Ki-67 index value and TP53 were evaluated using IHC and the cut-off values were 20% and 50%, respectively. Recurrence free survival (RFS) and breast cancer-specific survival (BCSS) was calculated using the Kaplan-Meier method and evaluated by the log-rank test or generalized Wicoxon test in stage 1 and 2 breast cancer. Results: In terms of the distribution of ER and PgR status, ER+/PgR- were frequently seen in postmenopausal patients (13.7% vs 6.8%, respectively). Patients with ER+/PgR-and HER2 negative tumors had significantly smaller tumors, lower Ki-67 values, and a lower nuclear grade in the postmenopausal group compared with those in the premenopausal group. Moreover, RFS trended to be better in the postmenopausal group (p = 0.06), but there was no significant difference. BCSS was significantly higher in the postmenopausal cases (p = 0.001). On the other hand, in patients with ER+/PgR+ tumors, there was no significant difference in RFS and BCSS between the post- and pre-menopausal groups. Conclusion: The ER+/PgR- tumors were more commonly seen in postmenopausal patients. The biological characteristics of ER+/PgR- tumors were significantly different in terms of the Ki-67 index value, nuclear grade, and the prognosis (BCSS and RFS) between pre- and postmenopausal status. Moreover, the postmenopausal group had a more favorable biology and prognosis than the premenopausal group. Therefore, the findings in this study indicate that menopausal status is related to the biology and prognosis in patients with ER+/PgR- tumors. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-05-06.

Expression and Significance of ER, PR, VEGF, CA15-3, CA125 and CEA in Judging the Prognosis of Breast Cancer

To explore the expression and significance of estrogen receptor (ER), progestrone receptor (PR), vascular endothelial growth factor (VEGF), CA15-3, CA125 and carcinoma embryonic antigen (CEA) expression in judging the prognosis of breast cancer. Sixty-five patients with breast cancer undergoing operations in the general surgery department were considered as the observation group, and 50 healthy outpatients of our hospital as the control group. Cubital venous blood was drawn in the morning from fasting patients in the two groups and chemiluminescence immunoassays were used to detect the levels of CA15-3, CA125 and CEA in serum. The follow-up duration was from 4 months to 2 years, and change in levels of the indicators was detected by dynamically drawing blood. After surgery, cancer tissue samples of patients in observation group remained on file (the non-recurrent patients were biopsied). Immunohistochemistry was applied to determine the expression of ER, PR and VEGF in tissue. The effective rate of 12 patients with negative ER and PR expression was 33.3% in the observation group, being associated with prognosis to varying extents. Serum CA15-3, CA125 and CEA in the observation group were all significantly higher than in control group (p<0.01). With increase in pathological staging, levels of serum CA15-3, CA125 and CEA gradually increased (p<0.01). Levels in patients with lymph node metastasis were markedly higher than in those without (p<0.01). In addition, values with distal lymph node metastasis were notably higher than with adjacent lymph node metastasis (p<0.01). The postoperative follow-up results revealed that positive VEGF and levels of serum VEGF, CA15-3, CA125 and CEA in recurrence group were obviously higher than in non-recurrence group (p<0.01). Joint detection of ER and PR expression as well as levels of serum VEGF, CA15-3, CA125 and CEA is meaningful and can guide the diagnosis and treatment for breast cancer.

Estrogen receptor β (ERβ) is a novel prognostic marker of recurrence survival in non-muscle-invasive bladder cancer potentially by inhibiting cadherin switch

The function and significance of estrogen receptor β (ERβ) in bladder cancer remains a field of hot debate. In this study, we aimed to (a) evaluate ERβ as a novel prognostic marker of recurrence free survival; and (b) digest the underlying mechanism by elucidating the relationship between ERβ expression and cadherin switch. We examined the expression levels of ERβ, E-cadherin and N-cadherin in 42 initial non-muscle-invasive urothelial bladder carcinomas via immunohistochemistry. Correlation analysis was performed among ERβ expression, cadherin switch and recurrence free survival. Moreover, in vitro studies were performed to validate the identified correlation using two bladder cancer cell lines RT4 and 253J. Upon stimulation with an ERβ selective agonist diarylpropionitrile, E-cadherin, N-cadherin expressions; cell migration and invasion capacity were assessed. Expression of ERβ protein was seen in 34 bladder cancer cases (80.9%), and 21 (50%) specimens showed non-cadherin switch (positive E-cadherin and negative N-cadherin). ERβ expression and the non-cadherin switch are both accompanied with better recurrence free survival. Also, the least ERβ expression was observed in specimens that undergo cadherin switch. Moreover, these results were consistent with our observations in bladder cancer RT4 and 253J cell lines studies. Diarylpropionitrile stimulation resulted in an increase in E-cadherin, a decrease in N-cadherin expression and abolished cell migration and invasion. ERβ is a prognostic marker of recurrence free rate in non-muscle-invasive bladder cancer, potentially through suppressing cadherin switch, and may act as a potential target for bladder cancer therapy.

Emerging Significance of Estrogen Receptor β in Gliomas

Primary brain tumors are heterogeneous group of intracranial lesions that are categorized into different subtypes based on their close morphology to their parental cell. Gliomas are the most common and deadliest tumors that accounts for ~70-80% of total brain tumors and the etiology of brain tumors is not completely understood [1-3]. Recent evidence suggests that the incidence of brain tumors is significantly higher in men than in women during the periods of active menstrual cycle suggesting the possible protective role of female sex hormones in the development of brain tumors [4-6]. Furthermore, a lower glioma incidence was reported for females who used exogenous hormones. The existence of a gender bias and the involvement of steroid hormones in the development of gliomas highlight the importance of this field in the glioma pathobiology. Estrogens are the steroid hormones that play a crucial role during development and differentiation of central nervous system [7,8], and locally synthesized estrogens play an essential role in neuroprotective functions [9]. The biological effects of estrogens are mediated through their cognate receptors: estrogen receptor alpha [ERα] and estrogen receptor beta [ERβ] [10]. ERβ has quite a different function than ERα and ERβ functions as a tissue-specific tumour suppressor with antiproliferative actions [10,11]. Several studies demonstrated that most of the gliomas express ERβ with negative or weak expression of ERα. ERβ is highly expressed in low-grade astrocytomas and non-neoplastic brain tissues. In contrast, most of the high-grade tumors express low ERβ expression and this lower ERβ expression correlates with histological malignancy and poor survival of patients [12-14]. Lower ERβ expression is significantly associated with higher expression of cytoplasmic BAG-1 [a coregulator of ER signalling] and worse clinical outcome [14]. Further, high expression of ERβ was an independent favourable prognostic factor [15].

Estrogen receptor β (ERβ) is a novel prognostic marker of recurrence survival in non-muscle-invasive bladder cancer potentially by inhibiting cadherin switch

The function and significance of estrogen receptor β (ERβ) in bladder cancer remains a field of hot debate. In this study, we aimed to (a) evaluate ERβ as a novel prognostic marker of recurrence-free survival and (b) digest the underlying mechanism by elucidating the relationship between ERβ expression and cadherin switch. We examined the expression levels of ERβ, E-cadherin and N-cadherin in 42 initial non-muscle-invasive urothelial bladder carcinomas via immunohistochemistry. Correlation analysis was performed among ERβ expression, cadherin switch, and recurrence-free survival. Moreover, in vitro studies were performed to validate the identified correlation using two bladder cancer cell lines RT4 and 253 J. Upon stimulation with an ERβ-selective agonist diarylpropionitrile, E-cadherin, N-cadherin expressions; cell migration, and invasion capacity were assessed. Expression of ERβ protein was seen in 34 bladder cancer cases (80.9%), and 21 (50%) specimens showed non-cadherin switch (positive E-cadherin and negative N-cadherin). ERβ expression and the non-cadherin switch are both accompanied with better recurrence-free survival. Also, the least ERβ expression was observed in specimens that undergo cadherin switch. Moreover, these results were consistent with our observations in bladder cancer RT4 and 253 J cell lines studies. Diarylpropionitrile stimulation resulted in an increase in E-cadherin, a decrease in N-cadherin expressions and abolished cell migration and invasion. ERβ is a prognostic marker of recurrence-free rate in non-muscle-invasive bladder cancer, potentially through suppressing cadherin switch, and may act as a potential target for bladder cancer therapy.

Expression and significance of estrogen receptor α and β in prostate cancer and peri-cancer tissue

Objective To investigate the expression of estrogen receptor (ER) α and β in human prostate cancer (PC), peri-cancer tissue and benign prostatic hyperplasia (BPH) tissue, and to discuss the role of estrogen receptor in prostate cancer. Methods The expression of ERα and ERβ in PC (n=28), peri-cancer tissue (n=28) and BPH (n=29) were detected by immunohistochemistry with En vision method. The ERα and ERβ expression were compared among different tissues by chisquare. The relationship between ER expression and related clinicopathologic features was statistically analyzed by spearman rank collection. Results ERα was localized dominantly in the stromal cell of PC. There were significant differences of the expression of ERα in PC, peri-cancer tissue and BPH tissue (epithelial cell 0%, 14%, 24%, P＜0. 05; stromal cell 57%, 68%, 31%,P＜0. 05). ERβ was localized in both epithelial and stromal cell of PC. There were significant differences of the expression of ERβ in PC, peri-cancer tissue and BPH tissue (epithelial cell 39%, 64%, 29%, P＜0.01; stromal cell 50%, 75%, 79%, P＜0.05). There was a significant difference of the expression of ERβ in different Gleason scores of PC tissue. Conclusions ERα is localized in the stromal cell of PC tissue.ERβ is localized in both epithelial and stromal cell of PC tissue. The ERβ might be related to the tumor differentiation of PC. Key words: Estrogen receptor alpha; Estrogen receptor beta; Prostatic neoplasms; Carcinoma; Prostatic hyperplasia

Significance of estrogen receptor 1 (ESR-1) gene imbalances in colon and hepatocellular carcinomas based on tissue microarrays analysis

Estrogen receptor alpha-encoded by ESR1 gene-overexpression correlates with prognosis and response to specific chemotherapy in breast adenocarcinoma cases. Mechanisms of ESR-1 deregulation in carcinomas remain under investigation. To analyze ESR1 in carcinomas of different histogenesis. Using tissue microarray technology, 172 primary carcinomas including breast ductal adenocarcinomas (n=60), hepatocellular carcinomas (n=52), and colon adenocarcinomas (n=60) were cored and re-embedded in three paraffin blocks. Initial diagnosis was based on liquid based cytology (LiquiPrep/ThinPrep). Immunohistochemistry and fluorescence in situ hybridization were performed. Quantitative evaluation of ER-a protein levels was assessed by applying digital image analysis. ER-a overexpression was observed in 41/60 (68.3%), 23/52 (44.2%) and 4/60 (6.6%) cases, respectively. ESR1 gene multiple copies were confirmed in 13/60 (21.6%) breast adenocarcinomas, but high amplification only in 8/13 (62.8%). Allelic absence was identified in 3/52 (5.7%) hepatocellular carcinomas, whereas colon adenocarcinomas demonstrated gene gains in 5/60 (8.3%) cases referred to chr 6 aneuploidy and not to amplification. ER-a overall expression was associated strongly to ESR1 gene copies only in breast carcinoma (P=0.036). ESR-1 gene overexpression happens frequently in breast cancer, but only a subset of them are high amplified cases correlated to increased response rates in hormonal therapy (tamoxifen). Absence of this mechanism in hepatocellular and colon carcinomas maybe is a negative factor for applying this therapy. This is a pattern of histo-genetic depended targeted therapeutic strategy.

The expression and significance of estrogen and progesterone receptor, HER-2 and p53 in endometrial carcinoma

Objective To investigate the expression and clinical significance of estrogen receptor (ER) ,progesterone receptor (PR), HER-2 and p53 in endometrial carcinoma. Methods The immunohis-tostaining of 162 cases of endometrial carcinoma was detected for ER, PR, HER-2 and 1053 expression, and the relationship between histological grade, depth of invasion and lymph node metastasis was analyzed. Results In 162 cases of endometrial carcinoma, the positive rate of ER, PR, HER2 and p53 was 53.7% ,61.1%, 18.5% and 33. 3% ,respectly. The expression of ER and PR was related to the histological grade or endometrial adeno-carcinoma,but without relationship to the invnsive depth and lymph node metastasis. The expression of HER-2 and p53 was related the invasive depth, and HER-2 expression was related lymph node metastasis. Conclusion The detection of ER, PR, HER-2 and p53 expression in endometrial carcinoma helped to access the prognosis and formulate individualized treatment programs. Key words: Endometrial cancer; Estrogen receptor; progesterone receptor; HER-2 ; p53 ; Immunohistechemistry

The significance of estrogen receptor β in 301 surgically treated non–small cell lung cancers

Estrogen receptor expression in lung cancer has been understudied, particularly in light of its potential biologic importance in the epidemic of lung cancer in women. The expression of estrogen receptors was investigated to better understand the possible role of sex hormones in lung cancer. A total of 301 patients with surgically resected non-small cell lung cancers of stages I to III were explored. Sections of paraffin-embedded tumor samples were stained with estrogen receptor alpha and estrogen receptor beta antibodies. Tumors with moderate-to-strong nuclear staining in at least 50% of the tumor cells were scored as positive for overexpression. The overall frequency of overexpression for estrogen receptor beta was 45.8% (138/301). It was detected most frequently in female patients (in 54.3% of 127 tumors vs 39.7% of 174 tumors in men, P = .012). However, there was no estrogen receptor alpha nuclear staining detectable in non-small cell lung cancers. Interestingly, a significant correlation between estrogen receptor beta expression, stage of disease, grade of differentiation, smoking status, vascular invasion, and survival in patients with stage II and III disease was found. By using multivariate analysis of survival among patients with stage II and III disease, estrogen receptor beta overexpression, stage II tumor, well differentiation, nonsmoking status, and lack of vascular invasion were significantly favorable prognostic factors. The results presented here show for the first time that immunohistochemical expression of estrogen receptor beta can be used as a prognostic indicator in patients with surgically resected stage II and III non-small cell lung cancers. These observations might offer a possibility for hormonal therapy in patients with lung cancer.

Expression of Cathepsin D in Colorectal Adenocarcinomas: Correlation with Clinicopathologic Features

Expression of Cathepsin D in Colorectal Adenocarcinomas: Correlation with Clinicopathologic Features

Relevance of ER to the Development of Endometrial Hyperplasia and Adenocarcinoma.

Estrogen has an important role in both the etiology and treatment of hormone-dependent endometrial cancers, although the mechanism remains elusive. To definethe role of estrogen-mediated signaling we investigated the biological significance of estrogen receptors (ER) in NIH3T3 cell transformation via the [ &sup12; Val ] K-Ras mutant. This mutant enhanced the steady state level and transcriptional activity of ER. In addition, overexpression of both wild type K-Ras and ER transformed NIH3T3 cells. Co-expression of the progesterone receptor (PR) with mutant K-Ras led to suppression of tumorigenicity and inhibition of ER activation. The antisense oligomers complementary to ER suppressed proliferation and transformed phenotypes of K12V cells. These observations support the importance of ER in Ras-mediated cell transformation. To address whether ER activation is also important in the development of human endometrial cancers, we investigated ER and PR expression levels in premalignant and malignant endometrial lesions. The results suggested the implication of ER abundance in endometrial hyperplasias, though modulation of PR expression by ER was retained. G1 adenocarcinoma also expressed higher levels of ER while PR modulation by ER was abrogated. These data implied the importance of ER activitiesin endometrial hyperplasia and G1 adenocarcinoma development.

Clinical Significance of Estrogen Receptor Àin Breast Cancer.

To estimate the clinical significance of estrogen receptor (ER) beta in breast cancer we reviewed some reports and compared them with our preliminary results. The structure of ERbetais similar to that of ER alpha. The DNA binding domain of ER beta is 96% conserved compared with ER alpha, and the ligand binding domain shows 58% conserved residues, suggesting that both receptors can bind estrogen responsiveelements on target genes and that they may also bind similar ligand. The targettissues of ER beta such as testis, prostate, lung, brain, thymus, and ovary, are different from those of ER alpha, ovary, uterus, endometrium, and breast. Although the function of ER beta in breast cancer progression is not well understood, 30-50% of breast cancers may express ER beta mRNA signals. Additionally, ER beta may be auseful prognostic factor in patients with breast cancer, because tumors that co-expressed ER alpha and ER beta might be node positive and tend to be of higher grade.Further characterization of the function of ER beta and its isoforms in breast cancer is warranted.

Steroid hormones and their receptors in the brain

Steroid hormones regulate several important functions of the brain by altering the expression of particular genes through their receptors. First in this paper the localization of glucocorticoid receptor immunoreactivity and mRNA in the brain was examined. Second biphasic effects of glucocorticoid on the hippocampus was described and particular emphasis was given on the apoptosis. Third the significance of estrogen receptor in the sexually dimorphic areas was discussed. These results suggest that steroids modulate the gene expression along with the alteration of cell structures in a different manner in a tissue-specific pattern.

690 Prognostic significance of estrogen receptors in 405 primary breast cancers (B.C.): A comparison of immunohistochemical (ICA) and biochemical (DCC) methods

ER were determined on 405 primary b.c. by both biochemical and immunoistochemical methods. The aim of this study was to evaluate if one of the two methods is more predictive of prognosis. We considered ERDCC + if ≥ 10 f mol/mg and ERICA+ if ≥ 45% of cells were stained. Product-limit method and Cox's proportional hazard model were used for the statistical analysis. The median follow-up was 40 months (range 4–95); 98 pts relapsed and 48 died. There is a close association between ERICA and ERDCC (concordance: 81.5%). ERICA status was significantly associated with both DFS and OS (higher in ERICA+); ERDCC status was significantly associated only with OS (higher in ERDCC+). Similar results were obtained when adjustments for the effect of other prognostic variables (pT, pN, age) were considered. A comparison of DFS and OS when ERICA and ERDCC status were jointly evaluated showed that these methods gave quite similar information on prognosis, so that it is possible to use only one technique.