Nuclear androgen receptor staining in bone metastases is related to a poor outcome in prostate cancer patients

Crnalic, Sead; Hörnberg, Emma; Wikström, Pernilla; Lerner, Ulf H.; Tieva, Åse; Svensson, Olle; Widmark, Anders; Bergh, Anders

doi:10.1677/erc-10-0059

Cited by 45 publications

(68 citation statements)

References 31 publications

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“…In human PCa patients, 90% of PCa metastases occur in bone[35], and the majority have strong expression of nuclear AR[158]. In the limited GEM models that develop metastatic bone lesions, the penetrance varies from “rare” up to about 17%.…”

Section: Discussionmentioning

confidence: 99%

Mouse models of prostate cancer: picking the best model for the question

Grabowska

DeGraff

et al. 2014

Cancer Metastasis Rev

109

102

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When the NIH Mouse Models of Human Cancer Consortium (MMCC) initiated the Prostate Steering Committee 15 years ago, there were no genetically engineered mouse (GEM) models of prostate cancer (PCa). Today, a PubMed search for “prostate cancer mouse model” yields 3,200 publications and this list continues to grow. The first generation of GEM utilized the newly discovered and characterized probasin (PB) promoter driving viral oncogenes such as SV40 large T antigen to yield the LADY and TRAMP models. As the PCa research field has matured, the second generation of models has incorporated the single and multiple molecular changes observed in human disease, such as loss of PTEN and over-expression of Myc. Application of these models has revealed that mice are particularly resistant to developing invasive PCa, and once they achieve invasive disease, the PCa rarely resembles human disease. Nevertheless, these models and their application have provided vital information on human PCa progression. The aim of this review is to provide a brief primer on mouse and human prostate histology and pathology, provide descriptions of mouse models, as well as attempt to answer the age old question: Which GEM model of PCa is the best for my research question?

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Section: Discussionmentioning

confidence: 99%

Mouse models of prostate cancer: picking the best model for the question

Grabowska

DeGraff

et al. 2014

Cancer Metastasis Rev

109

102

View full text Add to dashboard Cite

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“…22,23 Since AR overexpression is a late event in the progression of prostate cancer, AR is a potential marker for metastatic prostate cancer. Crnalic et al 22 showed that only two cases out of 58 investigated bone metastases were negative for AR. Concordant with these findings, we also observed a high-expression frequency for AR in distant metastases (91%).…”

Section: Discussionmentioning

confidence: 99%

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Queisser¹,

Hagedorn²,

Braun³

et al. 2015

Modern Pathology

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Prostate cancer is mostly diagnosed at an early stage; however, some tumors are diagnosed in a metastatic stage as cancer of unknown primary origin. In order to allow specific treatment in the case of prostate cancer presenting as cancer of unknown primary origin, it is important to determine the tumor origin. Prostate-specific antigen is used as a diagnostic marker for prostate cancer but the expression declines with progression to castration-resistant prostate cancer. Aim of this study was to identify the most informative marker constellation, which is able to detect metastatic prostate cancer at high sensitivity. The widely used prostate cancer markers such as prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene were investigated for their sensitivity to detect prostatic origin of metastases. Expression of prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene was determined on archived tissue specimens consisting of benign prostatic tissue (n ¼ 9), primary prostate cancer (n ¼ 79), lymph node metastases (n ¼ 58), and distant metastases (n ¼ 39) using immunohistochemistry. The staining intensity was categorized as negative (0), weak (1), moderate (2), and strong (3). All markers except ETS-related gene were able to detect at least 70% of lymph node metastases and distant metastases, with prostate-specific antigen, androgen receptor, and prostate-specific membrane antigen having the highest sensitivity (97%, 91%, and 94%, respectively). A further increase of the sensitivity up to 98% and 100% could be achieved by the combination of prostate-specific antigen, prostate-specific membrane antigen, or androgen receptor for lymph node metastases and for distant metastases, respectively. The same sensitivity could be reached by combining prostate-specific membrane antigen and prostein. Our data show that a combined staining of at least two prostate markers should be utilized to identify metastases as originating from prostate cancer. Modern Pathology (2015) 28, 138-145; doi:10.1038/modpathol.2014 published online 13 June 2014 Prostate cancer is the most commonly diagnosed non-epidermal cancer and second-most common cancer-related cause of death in men in the western world. 1 The patients' death is often caused by the development of castration-resistant prostate cancer. Most prostate cancers are detected early in a localized stage; however, in some cases, metastases can be the first manifestation of a prostate cancer. 2 Unlike other carcinomas, hormone-sensitive prostate cancer responds to hormonal therapy and therefore the identification of the tumor origin is important in order to allow specific treatment. Male patients with a metastatic adenocarcinoma are routinely assessed for prostatic origin using prostate-specific immunohistochemistry markers like prostate-specific antigen (PSA). 3 PSA is highly expressed in benign prosta...

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“…Heterogeneity also extends to the distribution and intensity of AR expression, as revealed by immunohistochemical studies of CRPC bone metastases 88, 90–92 . For example, in a study with 44 CRPC bone metastases, 58.1% of patients had moderate (30.4% of cases) to intense (69.6% of cases) AR staining in 76–100% of the tumor cells, whereas 8.8% of the patients in the study had AR staining in just 1–25% of tumor cells 92 . Thus, metastatic CRPC can exist as a mixture of cells displaying a range of AR expression levels.…”

Section: Complete Androgen Receptor Independencementioning

confidence: 92%

Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer

2015

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Preface Over the past ten years, preclinical studies implicating sustained androgen receptor (AR) signaling as the primary driver of castration resistant prostate cancer (CRPC) led to the development of novel agents targeting the AR pathway that are now in widespread clinical use. These drugs prolong survival of patients with late stage prostate cancer but are not curative. In this review, we highlight emerging mechanisms of acquired resistance to these contemporary therapies, which fall into the three broad categories of restored AR signaling, AR bypass signaling and complete AR independence. This diverse spectrum of resistance mechanisms presents new challenges for long term disease control, which may be addressable through early use of combination therapies guided by recent insights from genomic landscape studies of CRPC.

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Nuclear androgen receptor staining in bone metastases is related to a poor outcome in prostate cancer patients

Cited by 45 publications

References 31 publications

Mouse models of prostate cancer: picking the best model for the question

Mouse models of prostate cancer: picking the best model for the question

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer

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