Tumor focality in prostate cancer: implications for focal therapy

Karavitakis, Markos; Ahmed, Hashim U.; Abel, Paul; Hazell, Steven; Winkler, Mathias

doi:10.1038/nrclinonc.2010.190

Cited by 75 publications

(36 citation statements)

References 94 publications

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“…The focal heterogeneity in staining profiles concerned both, the amount of immunoreactive cells as well as the intensity of the staining. This result may be due to the known heterogeneous and multifocal nature of PCa (Karavitakis et al 2011). Interestingly, MED12 expression was more homogeneous in CRPC tissues compared with primary PCa and lymph node metastasis.…”

Section: Discussionmentioning

confidence: 57%

MED12 overexpression is a frequent event in castration-resistant prostate cancer

Shaikhibrahim¹,

Offermann²,

Braun³

et al. 2014

Endocrine-Related Cancer

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In a recent effort to unravel the molecular basis of prostate cancer (PCa), Barbieri and colleagues using whole-exome sequencing identified a novel recurrently mutated gene, MED12, in 5.4% of primary PCa. MED12, encoding a subunit of the Mediator complex, is a transducer of Wnt/b-catenin signaling, linked to modulation of hedgehog signaling and to the regulation of transforming growth factor beta (TGFb)-receptor signaling. Therefore, these studies prompted us to investigate the relevance of MED12 in PCa. Expression of MED12, SMAD3 phosphorylation, and proliferation markers was assessed by immunohistochemistry on tissue microarrays from 633 patients. siRNA-mediated knockdown of MED12 was carried out on PCa cell lines followed by cellular proliferation assays, cell cycle analysis, apoptosis assays, and treatments with recombinant TGFb3. We found nuclear overexpression of MED12 in 40% (28/70) of distant metastatic castration-resistant prostate cancer (CRPC MET ) and 21% (19/90) of local-recurrent CRPC (CRPC LOC ) in comparison with frequencies of less than 11% in androgen-sensitive PCa, and no overexpression in benign prostatic tissues. MED12 expression was significantly correlated with high proliferative activity in PCa tissues, whereas knockdown of MED12 decreased proliferation, reduced G1-to S-phase transition, and increased the expression of the cell cycle inhibitor p27. TGFb signaling activation associates with MED12 nuclear overexpression in tissues and results in a strong increase in MED12 nuclear expression in cell lines. Furthermore, MED12 knockdown

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Section: Discussionmentioning

confidence: 57%

MED12 overexpression is a frequent event in castration-resistant prostate cancer

Shaikhibrahim¹,

Offermann²,

Braun³

et al. 2014

Endocrine-Related Cancer

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“…Multifocality occurs in 56-87% of prostate adenocarcinomas [46]. Multifocal lesions could imply a level of genetic predisposition in the development of prostate carcinoma [47,48].…”

Section: Genetic/molecular Heterogeneitymentioning

confidence: 99%

The Heterogeneity of Prostate Cancer: A Practical Approach

Tolkach¹,

Kristiansen²

2018

Pathobiology

103

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Prostate cancer is a paradigm tumor model for heterogeneity in almost every sense. Its clinical, spatial, and morphological heterogeneity divided by the high-level molecular genetic diversity outline the complexity of this disease in the clinical and research settings. In this review, we summarize the main aspects of prostate cancer heterogeneity at different levels, with special attention given to the spatial heterogeneity within the prostate, and to the standard morphological heterogeneity, with respect to tumor grading and modern classifications. We also cover the complex issue of molecular genetic heterogeneity, discussing it in the context of the current evidence of the genetic characterization of prostate carcinoma; the interpatient, intertumoral (multifocal disease), and intratumoral heterogeneity; tumor clonality; and metastatic disease. Clinical and research implications are summarized and serve to address the most pertinent problems stemming from the extreme heterogeneity of prostate cancer.

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“…Recent evidence supports the concept of an index lesion or lesions that are clinically significant by volume. 28,29 Our use of maximum cancer core length as an indicator of disease burden has not been extensively validated. However, our previous study 22 and that of others 30 revealed close correlation between CCLmax and tumor volume when a systematic sampling strategy was used.…”

Section: Discussionmentioning

confidence: 99%

The Accuracy of Different Biopsy Strategies for the Detection of Clinically Important Prostate Cancer: A Computer Simulation

Lecornet

Ahmed

et al. 2012

Journal of Urology

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To our knowledge our biopsy simulation study is the first to evaluate the performance of different sampling strategies to detect clinically important prostate cancer in a population that better reflects the demographics of a screened cohort. Compared to other strategies standard transrectal ultrasound biopsy performs poorly for detecting clinically important cancer. Marginal improvement can be achieved using additional cores placed anterior but the performance attained by template prostate mapping is optimal.

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Tumor focality in prostate cancer: implications for focal therapy

Cited by 75 publications

References 94 publications

MED12 overexpression is a frequent event in castration-resistant prostate cancer

MED12 overexpression is a frequent event in castration-resistant prostate cancer

The Heterogeneity of Prostate Cancer: A Practical Approach

The Accuracy of Different Biopsy Strategies for the Detection of Clinically Important Prostate Cancer: A Computer Simulation

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