Image analysis of androgen receptor immunostaining in metastatic prostate cancer heterogeneity as a predictor of response to hormonal therapy

Sadi, Marcus Vinícius; Barrack, Evelyn R.

doi:10.1002/1097-0142(19930415)71:8<2574::aid-cncr2820710823>3.0.co;2-1

Cited by 111 publications

(59 citation statements)

References 18 publications

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“…Similar observation was reported by several other authors. 12,[21][22][23] In a prostate cancer specimen, AR staining in the epithelium is heterogenous, with a marked decrease in ARpositive cells occurring in less differentiated tumors. 24 The possibility that increased heterogeneity of cellular staining may be present during hormonal therapy arose from our data.…”

Section: Discussionmentioning

confidence: 99%

“…This may suggest the possibility that AR mutations may not be involved in all cases of therapy resistance and that additional mechanisms contributing to tumor recurrence also need to be considered. 22 It is not known whether AR gene mutations in hormone-refractory disease arose during androgen ablation therapy or were already present prior to therapy. The present study indicates that AR gene mutations may not exist in a subset of early stage or even advanced stage primary prostate tumors prior to initiation of hormonal therapy.…”

Section: Discussionmentioning

confidence: 99%

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Expression and somatic mutation on androgen receptor gene in prostate cancer

et al. 2002

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Background : Lack of androgen receptor (AR) expression or mutation on the AR gene creates the tendency for androgen independence and progression of prostate cancer. However, the association between the progression and AR expression or mutations is still controversial. In this study, we evaluated the prognostic significance of AR expression and mutations in prostate cancers. Methods : Forty-two prostate adenocarcinomas and three lymph node metastatic lesions sampled prior to hormonal therapy were included in this study; AR expression was analyzed immunohistochemically using an antibody against AR and the result was scored as the percentage of AR-positive tumor cells in the total tumor cells. Polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing were used to detect AR mutations. Results : Our study revealed the average AR expression in the prostate adenocarcinoma was 52.2 ± 27.1%, which was significantly lower than that in the adjacent non-tumorous prostate tissue (68.3 ± 18.3% in average) ( P < 0.001). A significant correlation was obtained between progressionfree survival and AR expression ( P < 0.01). By SSCP analysis, three silent mutations (T649T, E709E and E711E) were detected in three separate prostate carcinomas. Conclusion : We conclude that AR expression is a useful prognostic indicator for tumor progression. Androgen receptor mutation may be an uncommon molecular event in untreated prostate cancer in Japanese men.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Expression and somatic mutation on androgen receptor gene in prostate cancer

et al. 2002

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“…These authors were the first to report that AR immunostaining appeared similar in early CaP and benign prostate tissue. These results were contrasted with studies of advanced CaP from their own laboratory [21] and from others [22][23][24][25] where reduced AR immunoreactivity and increased heterogeneity of cellular staining was observed. They attributed the similar findings in early CaP and benign prostate tissue to the lack of development of greater genetic instability and altered androgen sensitivity, which they believed a characteristic of advanced CaP, especially after administration of ADT.…”

Section: Androgen-receptor Expression In the Epithelia Of Clinically mentioning

confidence: 99%

“…[39] However, they subsequently reported that the heterogeneity of expression of AR predicted response to ADT. [25] A series of studies that took advantage of the ability to examine archival tissue and to more precisely quantitate AR expression using image analysis techniques have confirmed these results. Tilley's group used video image analysis and an affinity-purified polyclonal antibody directed against the N terminus of AR to predict perfectly the outcome after ADT of 21 patients with advanced CaP.…”

Section: Androgen Receptor In Advanced Prostate Cancer Androgen Recepmentioning

confidence: 99%

“…Mean optical density (MOD) measured using image analysis was found to be more accurate and reproducible for measuring AR expression, but object identification remained difficult. Investigators used a light pen to encircle [25] or a sampling window [41] to select areas of malignant nuclei for optical density measurement. However, these interactive image analysis methods were tedious, and user bias influenced the measurements.…”

Section: Accurate Measurement Of Androgen-receptor Expression In Clinmentioning

confidence: 99%

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A role for the androgen-receptor in clinically localized and advanced prostate cancer

Mohler

2008

Best Practice & Research Clinical Endocrinology & Metab

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Earlier studies of androgen-receptor (AR) expression using frozen prostate tissue, and later studies using archived specimens, produced the consensus that ligand-stabilized AR is nuclear, AR expression is similar in benign epithelia and stroma, AR expression is greater in secretory epithelia than basal cells, and AR expression is more variable in prostate cancer (CaP) than in benign prostatic hyperplasia (BPH). Accurate measurement of AR expression remains technically challenging but necessary to evaluate the relevance of ARs to clinical CaP. Recent studies demonstrated that AR expression in epithelia and stroma may be prognostic in clinically localized CaP, and AR expression may play a role in racial differences in CaP mortality and predict response to androgen deprivation therapy. High levels of AR and AR-regulated gene expression indicate a central role for AR in growth regulation of castration-recurrent CaP. New treatments for the lethal phenotype of CaP require better understanding of AR transactivation during androgen deprivation therapy. Keywordsandrogen receptor; prostate cancer; quantitative video image analysis; immunohistochemistry Androgens are necessary for the development and growth of the prostate and for the development, growth and progression of prostate cancer (CaP). An American man is diagnosed with CaP every 3 minutes,[1] and the worldwide incidence of CaP is increasing an estimated 1.1% annually.[2] Despite increased use of digital rectal examination and serum prostatespecific antigen (PSA) measurement for early detection, approximately 30% of men treated with curative intent suffer CaP recurrence. These men, and those who present with locally advanced or metastatic CaP, can be palliated by androgen deprivation therapy (ADT), which causes regression of androgen-dependent CaP through programmed cell death.[3] Although there are many methods for medical and surgical ADT, the results of ADT remain unimproved since its discovery more than 60 years ago.[4] More than 80% of men with disseminated CaP demonstrate clinical or biochemical response that is associated with a mean life expectancy of approximately 3.5 years, in contrast to non-responders or untreated patients who live an average of 9 months. Regardless of the androgen responsiveness of incurable CaP, almost all patients succumb to castration-recurrent CaP because it responds poorly to all known therapies, and

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