Role Of Androgen Receptor Expression Research Articles

476P The role of androgen receptor expression and epigenetic regulation in adult-type diffuse gliomas

476P The role of androgen receptor expression and epigenetic regulation in adult-type diffuse gliomas

Role of androgen receptor expression in the metastatic potential of colorectal carcinoma

Background The prevalence of colorectal cancer (CRC) is widespread and associated with significant morbidity and deaths. In CRC, hormone receptors, such as androgen receptors (AR), are pathologically modified. Additional research is required to understand better its function and predictive and therapeutic value in CRC metastatic potential. Objective To assess the AR status in CRC primary tumors and metastatic lymph nodes. Methods Tissue microarray and immunohistochemical techniques were applied to 75 CRC cases with lymph node (LN) metastases. We correlate the results with all relevant clinicopathological indicators of prognostic relevance. Results and conclusion Out of the 75 cases that were analyzed, 16% of CRC primaries and 12% of LN metastases had nuclear AR that was focally positive. AR expression was significantly correlated with advanced age, conventional non-mucinous histology, lower grade, and arousal on top of adenoma. A deeper invasion was likewise linked to AR expression; however, this association was not statistically significant. AR expression has a positive prognostic influence since the median overall and disease-free survival of cases with positive AR expression in either primary carcinomas or LN metastases were significantly higher than that of cases with negative expression in both primary and LN metastases. We assume that AR expression in CRC has a positive prognostic influence.

The Role of Androgen Receptor Expression in Prostate Adenocarcinoma

Prostate cancer is one of the most common cancer worldwide, where South Sulawesi is included in four provinces with the highest prevalence of prostate cancer in Indonesia. Laboratorium Sentra Patologia Makassar (SDPM) stated that prostate cancer cases continue to rise each year. Androgen receptor (AR) plays a role in the growth and differentiation of male urogenital structures, both under normal and neoplastic conditions, the neoplastic condition is caused by the mechanism of the AR pathway which undergoes changes that continue in the development and progression of prostate lesions, both benign and malignant. Androgen receptors are generally found evenly distributed in the nuclei of glandular and stromal cells in prostate hyperplasia and vary widely in prostate cancer. These inventions show that AR inhibitors are used to treat prostate adenocarcinoma by inhibiting androgen synthesis. Assessment of AR expression can be used in determining therapy and predicting the success of hormonal therapy so that the prognosis of the disease is better. This study is conducted to learn more about AR expression in adenocarcinoma prostate grading. The type of this research is an observational analytical study with cross-sectional methods. Samples are taken based on consecutive sampling of as many as 77 respondents. There is a significant difference between AR expression score and histopathological feature of prostate adenocarcinoma WHO Grup Grade (p<0,001). In conclusion, there is a significant correlation between AR and WHO Grup Grade and could be used as important marker in grading adenocarcinoma prostate progression
 Keywords : Androgen receptor (AR); prostate adenocarcinoma; WHO Grup Grade

Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes.

HER2+ breast cancer (BC) is an aggressive subtype representing a genetically and biologically heterogeneous group of tumors resulting in variable prognosis and treatment response to HER2-targeted therapies according to estrogen (ER) and progesterone receptor (PR) expression. The relationship with androgen receptors (AR), a member of the steroid hormone’s family, is unwell known in BC. The present study aims to evaluate the prognostic impact of AR expression in HER2+ BC subtypes. A total of 695 BCs were selected and reviewed, AR, ER, PR and HER2 expression in tumor cells were examined by immunohistochemical method, and the SISH method was used in case of HER2 with equivocal immunohistochemical score (2+). A high prevalence of AR expression (91.5%) in BC HER+ was observed, with minimal differences between luminal and non-luminal tumor. According to steroid receptor expression, tumors were classified in four subgroups, including BC luminal and non-luminal HER2+ expressing or not AR. The luminal BC HER2 + AR+ was associated with lower histological grade, lower tumor size, higher PR expression and lower HER2 intensity of expression (2+). Also, the non-luminal tumors AR+ showed lower tumor size and lower prognostic stage but frequently higher grade and higher HER2 intensity of expression (3+). These findings should suggest a different progression of luminal and non-luminal tumors, both expressing AR, and allow us to speculate that the molecular mechanisms of AR, involved in the biology of BC HER2 + AR+, differ in relation to ER and PR expression. Moreover, AR expression may be a useful predictor of prognosis for overall survival (OS) in HER2+ BC subtypes. Our findings suggest that AR expression evaluation in clinical practice could be utilized in clinical oncology to establish different aggressiveness in BC HER2+ subtypes.

Prognostic role of androgen receptor expression in patients with metastatic triple negative breast cancer.

To evaluate the prognostic role of androgen receptor (AR) expression in patients with TNBC. The effect of the AR expression level in tumor tissue on overall survival depending on clinical, histological and immunohistochemical characteristics of the tumor was evaluated in 116patients with metastatic TNBC. The independent prognostic value of AR expression in patients with TNBC of different stages was shown. The median overall survival was higher in patients with AR-positive tumors compared with AR-negative tumors (57months vs 27months, p < 0.0001). Five-year survival since diagnosis in the group with AR-positive TNBC was 47.6 ± 8.3% vs 20.0 ± 5.3% in the group with AR-negative TNBC (p < 0.05). The results of our study indicate a favorable impact of AR expression on the overall survival of TNBC patients.

Role of androgen receptor expression in early stage ER+/PgR-/HER2- breast cancer.

Background:Progesterone receptor (PgR) negative breast cancer (BC) is an aggressive subtype with poor prognosis and reduced response to endocrine treatments. Several studies have suggested that androgen receptor (AR) expression is associated with a favorable tumor biology, longer recurrence free survival (RFS), and overall survival. In the literature no data exist regarding the role of AR expression in early stage estrogen receptor (ER)+/PgR– BCs. The aim of this study was to evaluate the prognostic role of AR expression in this setting.Patients and methods:This is a monocentric retrospective study in which 208 patients who underwent surgical intervention for ER+/PgR−/Human Epidermal growth factor Receptor 2 (HER2)– BC were included. The primary objective was to analyze the relationship between AR expression and RFS.Results:At a median follow-up of 77 months, 75 patients (36%) had a disease relapse (all sites included). AR expression was significantly higher in patients who did not relapse compared with those who relapsed with an impact on RFS (hazard ratio [HR] = 0.99, p = 0.025). Patients with AR expression ⩾80% had a lower risk of relapse compared with those with AR <80% (HR = 0.53, p = 0.008). In addition, breast tumors with higher AR expression had good biological features (low ki67 and nuclear grade) compared with BCs with lower AR expression, at least partly explaining the different outcome.Conclusions:The results of this study support the potential prognostic role of AR in patients with ER+/PgR− BCs and may contribute to the identification of subgroups of high-risk patients.

Prognostic Role of Androgen Receptor Expression in Surgically Resected Early Breast Cancer Patients.

PurposeEndocrine therapy is a standard treatment for hormone receptor-positive breast cancer, which accounts for 60%–75% of all breast cancer. Hormone receptor positivity is a prognostic and predictive biomarker in breast cancer. Approximately 50%–80% of breast cancer is also positive for androgen receptor (AR), but the prognostic and predictive value of AR expression in breast cancer is controversial. Here, we investigated AR expression and its prognostic value in patients with surgically resected breast cancer in Korea.MethodsWe retrospectively reviewed the medical records of patients who had surgically resected breast cancer to collect AR expression data and other clinicopathological data. The optimal cut-off for AR positivity was determined using a receiver operating characteristic curve analysis.ResultsWe reviewed 957 patients with surgically resected breast cancer from June 2012 to April 2013. The median follow-up was 62 months, and relapse events occurred in 101 (10.6%) patients. Unlike the cut-off value of 1% or 10% in previous reports, 35% was determined to be best for predicting relapse-free survival (RFS) in this study. At the cut-off value of 35%, 654 (68.4%) patients were AR-positive. AR expression was more prevalent in luminal A (87.6%) and luminal B (73.1%) types than in human epidermal growth factor receptor 2-positive (56.2%) or triple-negative (20.6%) types. AR expression of ≥ 35% was significantly related to longer RFS in a multivariate analysis (hazard ratio, 0.430; 95% confidence interval, 0.260–0.709; p = 0.001).ConclusionWe propose a cut-off value of 35% to best predict RFS in patients with surgically resected breast cancer. AR expression was positive in 68.4% of patients, and AR positivity was found to be an independent prognostic factor for longer RFS.

Role of androgen receptor expression in non-muscle-invasive bladder cancer: a systematic review and meta-analysis.

In order to evaluate the potential prognostic/predictive role of androgen receptor (AR) expression in non-muscle-invasive bladder cancer (NMIBC), and whether it may represent a therapeutic target, we conducted a systematic search of the literature using 'androgen receptor or AR', 'testosterone', 'bladder cancer' and 'non-muscle invasive bladder cancer or NMIBC' as keywords. Eleven studies met the inclusion/exclusion criteria. No significant association was found between AR status and patients' gender (p=0.232), tumor size (p=0.975), tumor stage (p=0.237), tumor grade (p=0.444), tumor multicentricity (p=0.397), concomitant CIS (p=0.316) and progression of disease (p=0.397). On the other hand, relative lack of AR expression was significantly correlated to recurrent disease (p=0.001). Evidence for a direct correlation between AR expression and recurrence-free survival of patients with NMIBC indicate ARs as potential markers of BC behavior; moreover, the finding of a role of androgen blockade therapy in improving survival highlights the potential clinical application of this pathway, which deserves to be further explored.

Prognostic role of androgen receptor expression in triple-negative breast cancer.

1076 Background: Expression of androgen receptor (AR) was reported to be associated with estrogen receptor (ER) expression and predict better disease-free survival (DFS) and overall survival (OS) in early breast cancer. The prognostic role of AR expression in triple-negative breast cancer (TNBC) is unclear. We performed a meta-analysis of published clinical studies to date. The Cancer Genome Atlas (TCGA) data was used to evaluate the association of AR expression with survival outcomes in TNBC. Methods: PubMed was searched for eligible clinical studies that investigated the association of AR expression with clinical outcomes (DFS and/or OS) of TNBC. Pooled hazards ratios (HRs) for survival outcomes with 95% confidence interval (CI) were calculated using Comprehensive MetaAnalysis (v2). AR mRNA expression, clinical information and survival data of breast cancer patients were extracted from the TCGA Data Portal. OS of TNBC patients with different levels of AR expression was compared using Cox-proportional ha...

The role of androgen receptor expression in the curative treatment of prostate cancer with radiotherapy: a pilot study.

The androgen receptor (AR) and its signaling pathway play an important role in the development and progression of prostate cancer (PCa). In the setting of primary treatment of PCa with radiotherapy (RT), where the AR can be expected to be of more importance, studies evaluating the AR expression are lacking. The goal of this research is to evaluate AR protein expression in hormone-naive PCa patients treated by RT and investigate its possible prognostic role. Primary biopsy samples of 18 patients treated with primary RT were analyzed including the corresponding clinical information. AR protein expression of the tumor epithelium (with highest Gleason pattern) and the surrounding stroma was quantified using the Quick score for steroid receptors. The differential expression between epithelium and stroma, respectively, between tumor and normal tissue (ΔTumor − ΔBenign >2 versus ≤2), was predictive for clinical progression-free survival in the biopsy samples (P = 0.014). Preliminary results of this research show already a promising role of differential AR expression in predicting clinical relapse after PCa treatment with primary EBRT. Further research is needed to validate these findings. Hopefully this can lead to a better understanding of PCa evolution and eventually lead to better therapy strategies.

Abstract 3654: Prognostic role of androgen receptor in bladder cancer

Abstract Aims: Hormone receptors are the prototype predictive marker in breast and prostate cancer. Hormone receptor positive cancers have a better prognosis, increased tropism to metastasize into the bones and respond to endocrine treatment options. The prognostic value of hormone receptor in urothelial carcinoma of the bladder (UCB) is less established. This may in part result from technical limitations of immunhistochemical detection methods. Interestingly, female gender has recently been identified as strong adverse factor in advanced UCB (May et al., 2011). By analyzing whole genome expression data from non-muscle invasive bladder cancer patients, we have evaluated the potential of top candidate genes (ESR1, PGR, AR, CYP19, HER2, RACGAP1) commonly used to stratify breast cancer patients to predict bladder cancer progression. In view of the gender specific effects, we have focused on the prognostic role of androgen receptor expression on tumor invasion, disease progression and survival. Methods: Affymetrix microarray data from 41 non-metastatic bladder cancer patients undergoing curative surgery were analyzed. Prognostic value of androgen receptor mRNA expression was analyzed by unsupervised Cluster analysis, partitioning tests, Mann Whitney tests and Kaplan Meier estimates of cancer specific survival. Results: Cluster analysis in the microarray date of the superficial UCB cohort identified a hormone receptor positive subtype and a proliferation dominated subtype of equal size. Androgen receptor expression was negatively associated with cancer specific death (r=−0,42; p=0,005), while proliferation correlated with increased risk of cancer specific death (r=0,46; p=0,003). In addition, low androgen receptor expression was associated with higher tumor stage (pTa vs pT1-4; p=0,017). In Kaplan Meier analysis, the cancer specific survival was significantly better in tumors exhibiting high androgen receptor levels (80% vs. 20 %; p&amp;lt;0,0001). Discussion: Resembling to some extent the situation in other cancer types, hormone receptors are prognostic factors in early stage bladder cancer. These results may also explain the recently described gender specific effects in bladder cancer. Moreover, these results raise the possibility, that UCB patients may be stratified according to their androgen receptor status in view of prognosis and putative endocrine therapy options. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3654. doi:1538-7445.AM2012-3654