Androgen receptor content of prostate carcinoma cells estimated by immunohistochemistry is related to prognosis of patients with stage D2 prostate carcinoma

Takeda, H.; Akakura, Koichiro; Masai, Motoyuki; Akimoto, Susumu; Yatani, Ryuichi; Shimazaki, Jun

doi:10.1002/(sici)1097-0142(19960301)77:5<934::aid-cncr20>3.0.co;2-3

Cited by 81 publications

(43 citation statements)

References 30 publications

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“…Finally, AR has recently been suggested to function as a tumor suppressor in epithelium to suppress prostate tumor invasion and metastasis [39]. Also, several reports have shown that higher AR expression and pretreatment testosterone levels predict better response to endocrine therapy [40]–[42]. Consequently, combined with our results, higher transactivated AR with shorter CAG repeats might inhibit prostate cancer metastasis and predict a good prognosis on ADT.…”

Section: Discussionsupporting

confidence: 76%

Molecular Markers in Sex Hormone Pathway Genes Associated with the Efficacy of Androgen-Deprivation Therapy for Prostate Cancer

Huang

et al. 2013

PLoS ONE

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Although most advanced prostate cancer patients respond to androgen-deprivation therapy (ADT), the efficacy is widely variable. We investigated whether the host genetic variations in sex hormone pathway genes are associated with the efficacy of ADT. A cohort of 645 patients with advanced prostate cancer treated with ADT was genotyped for 18 polymorphisms across 12 key genes involved in androgen and estrogen metabolism. We found that after adjusting for known risk factors in multivariate Cox regression models, AKR1C3 rs12529 and AR-CAG repeat length remained significantly associated with prostate cancer-specific mortality (PCSM) after ADT (P≤0.041). Furthermore, individuals carrying two unfavorable genotypes at these loci presented a 13.7-fold increased risk of PCSM compared with individuals carrying zero (P<0.001). Our results identify two candidate molecular markers in key genes of androgen and estrogen pathways associated with PCSM after ADT, establishing the role of pharmacogenomics in this therapy.

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Section: Discussionsupporting

confidence: 76%

Molecular Markers in Sex Hormone Pathway Genes Associated with the Efficacy of Androgen-Deprivation Therapy for Prostate Cancer

Huang

et al. 2013

PLoS ONE

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“…This was the first report of an association between nuclear AR content and hormonal response and might underline the “driving” AR transcriptional role. A study of 62 patients with untreated metastatic prostate cancer who received ADT showed that high immunohistochemical (IHC) AR content is a favorable prognostic indicator [8]. In addition, image IHC analysis of prostate cancer AR with a pattern/receptogram-oriented approach could accurately predict response to hormone therapy in patients with advanced stage, while AR heterogeneity was associated with poor prognosis in different studies [9–11].…”

Section: Potential Biomarkers Of Response To Hormonal Therapy (Tabmentioning

confidence: 99%

Predicting response to hormonal therapy and survival in men with hormone sensitive metastatic prostate cancer

Grivas

Robins

Hussain

2013

Critical Reviews in Oncology/Hematology

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Androgen deprivation is the cornerstone of the management of metastatic prostate cancer. Despite several decades of clinical experience with this therapy there are no standard predictive biomarkers for response. Although several candidate genetic, hormonal, inflammatory, biochemical, metabolic biomarkers have been suggested as potential predictors of response and outcome, none has been prospectively validated nor has proven clinical utility to date. There is significant heterogeneity in the depth and duration of hormonal response and in the natural history of advanced disease; therefore to better optimize/individualize therapy and for future development, identification of biomarkers is critical. This review summarizes the current data on the role of several candidate biomarkers that have been evaluated in the advanced/metastatic disease setting.

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“…Studies show that aberrant expression of the AR correlate with decreased differentiation and higher Gleason scores in prostate cancer [24][25][26]. Overexpression of the AR is a relatively common phenomena among AIPC patients with about 30% of prostate tumors that progress to androgen independence following androgen ablation expressing increased AR mRNA and protein [27,28].…”

Section: Androgen Receptor In Prostate Cancermentioning

confidence: 99%

Cross-Talk Between the Androgen Receptor and the Phosphatidylinositol 3-Kinase/Akt Pathway in Prostate Cancer

Wang¹,

Kreisberg²,

Ghosh³

2007

CCDT

127

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Prostate cancer is initially dependent on androgens for growth; hence, recurrent prostate is treated with androgen ablation which may result in progression to androgen independence characterized by a resistance to such therapy. Androgens bind to and activate the androgen receptor (AR), a member of the nuclear steroid receptor family of transcription factors, which regulates prostate cancer cell proliferation and survival in androgen-independent, as well as -dependent, tumors. Another pathway regulating proliferation and survival is the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Here we analyze reports in the literature indicating that these two pathways cooperate to regulate prostate tumor development and progression. Studies show that AR transcriptional activity and expression are regulated by Akt. In addition, androgens regulate the Akt pathway by both genomic and non-genomic effects. This explains why prostate tumors subjected to androgen ablation experience an increase in Akt phosphorylation, and suggest that the tumor compensates for the loss of one pathway with another. Different modes of interaction between the two pathways, including direct interaction, or regulation via downstream intermediates, such as the wnt/GSK-3beta/beta-catenin pathway, NF-kappaB, and the FOXO family of transcription factors, will be discussed. In addition, we will discuss the role of Akt in the interaction of the AR with upstream regulators of Akt phosphorylation, such as receptor tyrosine kinases of the EGF and IGF-1 receptor families and the tumor suppressor PTEN.

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Androgen receptor content of prostate carcinoma cells estimated by immunohistochemistry is related to prognosis of patients with stage D2 prostate carcinoma

Abstract: Androgen receptor content measured immunohistochemically is a useful prognostic indicator for patients with Stage D2 prostate carcinoma treated with endocrine therapy.

Cited by 81 publications

References 30 publications

Molecular Markers in Sex Hormone Pathway Genes Associated with the Efficacy of Androgen-Deprivation Therapy for Prostate Cancer

Molecular Markers in Sex Hormone Pathway Genes Associated with the Efficacy of Androgen-Deprivation Therapy for Prostate Cancer

Predicting response to hormonal therapy and survival in men with hormone sensitive metastatic prostate cancer

Cross-Talk Between the Androgen Receptor and the Phosphatidylinositol 3-Kinase/Akt Pathway in Prostate Cancer

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