MP17-12 MOLECULAR ALTERATIONS IN PROSTATE CANCER AND ASSOCIATION WITH MRI FEATURES

2015 ◽  
Vol 193 (4S) ◽  
Author(s):  
Daniel Lee ◽  
Jacqueline Fontugne ◽  
Naveen Gumpeni ◽  
Kyung Park ◽  
Theresa MacDonald ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Alterations ◽  
Mri Features

Molecular alterations in prostate cancer and association with MRI features

2017 ◽  
Vol 20 (4) ◽  
pp. 430-435 ◽  
Author(s):  
D Lee ◽  
J Fontugne ◽  
N Gumpeni ◽  
K Park ◽  
T Y MacDonald ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Alterations ◽  
Mri Features

scholarly journals N-cadherin increases after androgen deprivation and is associated with metastasis in prostate cancer

2010 ◽  
Vol 17 (2) ◽  
pp. 469-479 ◽  
Author(s):  
Karin Jennbacken ◽  
Tajana Tešan ◽  
Wanzhong Wang ◽  
Heléne Gustavsson ◽  
Jan-Erik Damber ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Neuroendocrine Differentiation ◽  
Hormonal Treatment ◽  
Androgen Deprivation ◽  
Prostate Tumors ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Molecular Alterations

Androgen-deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer. One factor that has been implicated in the metastatic process is the cell adhesion molecule N-cadherin. In this study, we investigated if the expression of N-cadherin was influenced by androgen deprivation and was associated with metastasis in prostate cancer. The effect of androgen deprivation on N-cadherin expression was initially studied in androgen-dependent (AD) LNCaP and androgen-independent (AI) LNCaP-19 and PC-3 prostate cancer cell lines. Expression of N-cadherin increased in the absence of androgens in AI LNCaP-19 primary tumors and metastases and also in vitro, but not in AI PC-3 tumors, indicating a possible involvement of the androgen receptor in the regulation of N-cadherin. N-cadherin was absent in AD LNCaP tumors. No clear associations between N-cadherin and factors related with epithelial–mesenchymal transition or neuroendocrine differentiation could be established. In addition, N-cadherin was evaluated by immunohistochemistry in human prostate tumors. Expression of N-cadherin was more frequently found in tumors from patients treated with ADT than in tumors from patients with no prior hormonal treatment. N-cadherin expression was also associated with metastasis and Gleason score. Furthermore, increased N-cadherin was detected in prostate cancer biopsies already 3 months after initiation of ADT when tumors were in a regressed state. In summary the results indicate that androgen deprivation induces N-cadherin in prostate tumors. Moreover, N-cadherin was increased in castration-resistant tumors in patients with established metastases. This might indicate that castration induces molecular alterations in the tumor cells, resulting in a more invasive and metastatic phenotype.

scholarly journals Molecular Alterations in Prostate Cancer as Diagnostic, Prognostic, and Therapeutic Targets

2008 ◽  
Vol 15 (6) ◽  
pp. 319-331 ◽  
Author(s):  
Bora Gurel ◽  
Tsuyoshi Iwata ◽  
Cheryl M. Koh ◽  
Srinivasan Yegnasubramanian ◽  
William G. Nelson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Therapeutic Targets ◽  
Molecular Alterations

scholarly journals An Emerging Landscape for Canonical and Actionable Molecular Alterations in Primary and Metastatic Prostate Cancer

2020 ◽  
Vol 19 (6) ◽  
pp. 1373-1382 ◽  
Author(s):  
Nancy A. Dawson ◽  
Matthew Zibelman ◽  
Timothy Lindsay ◽  
Rebecca A. Feldman ◽  
Michelle Saul ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Molecular Alterations

scholarly journals Association analysis between quantitative MRI features and hypoxia-related genetic profiles in prostate cancer: a pilot study

2019 ◽  
Vol 92 (1104) ◽  
pp. 20190373 ◽  
Author(s):  
Yu Sun ◽  
Scott Williams ◽  
David Byrne ◽  
Simon Keam ◽  
Hayley M. Reynolds ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pilot Study ◽  
Glucose Transporter ◽  
Pearson Correlation ◽  
Texture Features ◽  
Quantitative Mri ◽  
Imaging Features ◽  
Selective Treatment ◽  
Mri Features ◽  
Genetic Profiles

Objective: To investigate the association between multiparametric MRI (mpMRI) imaging features and hypoxia-related genetic profiles in prostate cancer. Methods: In vivo mpMRI was acquired from six patients prior to radical prostatectomy. Sequences included T2 weighted (T2W) imaging, diffusion-weighted imaging, dynamic contrast enhanced MRI and blood oxygen-level dependent imaging. Imaging data were co-registered with histology using three-dimensional deformable registration methods. Texture features were extracted from T2W images and parametric maps from functional MRI. Full transcriptome genetic profiles were obtained using next generation sequencing from the prostate specimens. Pearson correlation coefficients were calculated between mpMRI data and hypoxia-related gene expression levels. Results were validated using glucose transporter one immunohistochemistry (IHC). Results: Correlation analysis identified 34 candidate imaging features (six from the mpMRI data and 28 from T2W texture features). The IHC validation showed that 16 out of the 28 T2W texture features achieved weak but significant correlations (p < 0.05). Conclusions: Weak associations between mpMRI features and hypoxia gene expressions were found. This indicates the potential use of MRI in assessing hypoxia status in prostate cancer. Further validation is required due to the low correlation levels. Advances in knowledge: This is a pilot study using radiogenomics approaches to address hypoxia within the prostate, which provides an opportunity for hypoxia-guided selective treatment techniques.

Evidence for a field effect in early prostate cancer (PCa): Gene expression profiles in normal-appearing prostate tissue (NT) adjacent to tumor (T) as predictors of clinical outcome.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5029-5029 ◽  
Author(s):  
Eric A. Klein ◽  
Sara Moscovita Falzarano ◽  
Nan Zhang ◽  
Dejan Knezevic ◽  
Tara Maddala ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Field Effect ◽  
Proportional Hazards ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cox Proportional Hazards ◽  
Clinical Recurrence ◽  
Molecular Alterations ◽  
Cox Proportional Hazards Models

5029 Background: We previously identified genes whose expression predicts aggressive PCa (clinical recurrence (cR), prostate cancer death (PCD), adverse pathology) when assessed in histologically heterogeneous tumor foci and in biopsies (Klein ASCO 2012). These results enabled the definition of a multi-gene Genomic Prostate Score (GPS), which has been clinically validated (Cooperberg AUA 2013). There is interest regarding a possible field effect in PCa, i.e. molecular alterations throughout the gland that may influence PCa development. We conducted exploratory analyses to evaluate gene expression, including GPS, in adjacent normal-appearing tissue (NT) for prediction of cR and PCD. Methods: Cohort sampling was used to select 127 patients with and 374 without cR from 2,641 patients treated with RP for T1/T2 PCa. Expression of 732 genes was measured by qRT-PCR separately in T and NT (defined as > 3 mm from T) specimens. GPS (0-100 units) was determined using the genes and algorithm from the validation study. Analysis used Cox proportional hazards models and Storey’s false discovery rate (FDR) control. Results: 410 evaluable patients had paired T and NT. Of the 405 genes which were predictive of outcome in T (FDR < 20%), 289 (71%) showed similar but weaker effects in NT. 47 genes were associated with cR in NT (FDR < 20%), of which 34 also concordantly predicted cR in T (FDR < 20%). GPS assessed in NT significantly predicted time to cR (HR/20 units = 1.8; 95% CI: 1.3-2.4; p< 0.001) and PCD (HR/20 units = 1.9; 95% CI: 1.2-3.0; p = 0.005) but was less predictive than GPS in T (HR/20 units = 4.8 for cR; 95% CI: 3.7-6.2; p < 0.001 and HR/20 units = 6.9 for PCD; 95% CI: 4.4-10.7; p < 0.001). The strongest components of GPS in predicting cR and PCD in NT were stromal response and androgen signaling genes (p < 0.05); proliferation and cellular organization genes did not consistently provide a significant contribution in NT. Conclusions: These data indicate that gene expression profiles, including GPS, can predict outcome in NT, albeit more weakly than in tumor. These findings suggest that there is an underlying field effect associated with the development of aggressive PCa.

Radiogenomics of prostate cancer: Association between qunatitative multiparametric MRI features and PTEN.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 126-126 ◽  
Author(s):  
David James VanderWeele ◽  
Stephanie McCann ◽  
Xiaobing Fan ◽  
Tatjana Antic ◽  
Yulei Jiang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signal Intensity ◽  
Immunohistochemical Analysis ◽  
Fold Increase ◽  
Image Features ◽  
Pten Expression ◽  
New Paradigm ◽  
Clinical Images ◽  
Mri Features ◽  
Adc Values

126 Background: Better methods are needed to assess prior to prostatectomy the risk of aggressive prostate cancer. Radiogenomics is a promising new paradigm that aims to gain molecular and genomic insights from clinical images. Loss of PTEN expression correlates with clinically aggressive disease and is associated with a 7-fold increase in the risk of prostate cancer death. Methods: From 38 patients who had undergone multi-parametric prostate MRI prior to prostatectomy, a pathologist and a radiologist simultaneously identified 45 peripheral-zone cancer regions of interest (ROIs). Histologic sections of the cancer foci underwent immunohistochemical analysis and were scored according to percent of tumor cells expressing PTEN as: negative (0-20%), mixed (20-80%), or positive (80-100%). From the MRI ROIs, the average and 10th percentile ADC values, T2-weighted signal-intensity histogram skewness, and quantitative perfusion parameters were calculated. Both dynamic perfusion two-compartment model and an empirical mathematical model (EMM) were used to fit the average contrast concentration curves within the ROIs as a function of time. Associations between the quantitative image features and PTEN expression were analyzed with Pearson's correlation coefficient (r). Results: The PTEN scores were: positive (n = 21, 47%), mixed (n = 12, 27%), and negative (n = 12, 27%). Two perfusion imaging contrast uptake parameters obtained from EMM correlated with PTEN scores (r = 0.25, p < 0.1 and r = 0.43, p < 0.01), and T2-weighted signal-intensity skewness also showed some correlation tendency (r = −0.25, p < 0.1). No correlation was seen between mean ADC and 10th percentile ADC values and PTEN score. Conclusions: This preliminary study of radiogenomics of prostate cancer suggests that fast contrast uptake of cancer on DCE-MR imaging and a T2-weighted imaging feature are potentially associated with prostate cancer PTEN expression, which warrants further studies and validation.

scholarly journals Molecular Alterations during Progression of Prostate Cancer to Androgen Independence

2011 ◽  
Vol 57 (10) ◽  
pp. 1366-1375 ◽  
Author(s):  
Punit Saraon ◽  
Keith Jarvi ◽  
Eleftherios P Diamandis
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Androgen Independence ◽  
Molecular Alterations ◽  
Signaling Mechanisms ◽  
Hormonal Therapies ◽  
Epigenetic Signatures ◽  
Key Pathways ◽  
Androgen Independent

BACKGROUND Prostate cancer is the most commonly diagnosed cancer among men in North America and is a leading cause of death. Standard treatments include androgen deprivation therapy, which leads to improved clinical outcomes. However, over time, most tumors become androgen independent and no longer respond to hormonal therapies. Several mechanisms have been implicated in the progression of prostate cancer to androgen independence. CONTENT Most tumors that have become androgen independent still rely on androgen receptor (AR) signaling. Mechanisms that enhance AR signaling in androgen-depleted conditions include: AR gene amplification, AR mutations, changes in the balance of AR cofactors, increases in steroidogenic precursors, and activation via “outlaw” pathways. Along with AR signaling, various other AR-independent “bypass” pathways have been shown to operate aberrantly during androgen independence. Changes in the epigenetic signatures and microRNA concentrations have also been implicated in the development of androgen-independent prostate cancer. SUMMARY Understanding of the molecular mechanisms that lead to the development of androgen-independent prostate cancer will allow for improved therapeutic strategies that target key pathways and molecules that are essential for these cells to survive.

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