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 A Novel Correlation of Preoperative Gd-EOB-DTPA-contrast-enhanced MRI with FGFR4 Expression and Its Value in Targeted Therapy for Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Zhiqing Mo ◽  
Liling Long ◽  
Hao Ding ◽  
Xiaojiao Zhou
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Protein Expression ◽  
Signal Intensity ◽  
Image Features ◽  
Arterial Phase ◽  
Hepatobiliary Phase ◽  
Enhanced Mri ◽  
Mri Features ◽  
The Relationship

Abstract Purpose: To assess the relationship between preoperative gadolinium ethoxy-benzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) features and fibroblast growth factor receptor 4 (FGFR4) gene expression in hepatocellular carcinoma (HCC).Materials and methods: Fifty-nine HCC patients (54 males, 5 females) who underwent preoperative enhanced MRI were retrospectively enrolled in this study. Quantitative and qualitative features of Gd-EOB-DTPA-enhanced MRI were analyzed in these pathologically confirmed HCC patients. Immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) were performed to determine the mRNA and protein levels of FGFR4 in HCC. The relationship between these image features and the level of FGFR4 gene expression in HCC was evaluated by correlation analysis.Results: The FGFR4 mRNA and protein expression has significant correlation with the change of signal intensity in the phase of hepatobiliary, IHC analysis revealed significant correlation between the protein expression of FGFR4 and the qualitative enhanced MRI feature, mainly the manifestation of the intratumoral vessels at the arterial phase. Furthermore, the presence of intratumoral vessels (P =0.034, OR=4.71) and heterogeneous 3 signal performance in the hepatobiliary phase (P =0.008, OR=4.2) were identified as independent indicators for high FGFR4 expression in HCC. Conclusions: The findings demonstrate novel correlation between enhanced MRI features and FGFR4 gene expression, suggesting the heterogeneous signal intensity at the phase of hepatobiliary and the present of intratumoral vessels in the arterial phase as indicators for high FGFR4 expression in HCC. Our study may have clinical implication that enhanced MRI holds promise as useful modality in treatment selection of targeted therapies to HCC patients.

Intrahepatic mass-forming cholangiocarcinoma and solitary hypovascular liver metastases: is the differential diagnosis using diffusion-weighted MRI possible?

2017 ◽  
Vol 58 (12) ◽  
pp. 1417-1426 ◽  
Author(s):  
Jelena Djokić Kovač ◽  
Danijel Galun ◽  
Aleksandra Đurić-Stefanović ◽  
Gordana Lilić ◽  
Dragan Vasin ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Signal Intensity ◽  
Univariate Analysis ◽  
Arterial Phase ◽  
Primary Liver Tumor ◽  
Biliary Dilatation ◽  
Target Sign ◽  
Diffusion Weighted ◽  
Mri Features ◽  
Adc Values

Background Intrahepatic mass-forming cholangiocellular carcinoma (IMC) is the second most common primary liver tumor. The differentiation between IMC and solitary hypovascular liver metastases (SHLM) represents a diagnostic challenge due to many overlapping magnetic resonance imaging (MRI) features. Purpose To determine the value of diffusion-weighted imaging (DWI) in addition to conventional MRI for the distinction between intrahepatic mass-forming cholangiocarcinoma and solitary hypovascular liver metastases. Material and Methods Fifty-three patients with pathologically proven IMC (n = 31) and SHLM (n = 22) who had undergone MRI and DWI before surgery or percutaneous biopsy were enrolled in this study. The following MRI features were analyzed: the size and shape of the lesion, presence of capsular retraction and segmental biliary dilatation, T2-weighted (T2W) signal intensity, the presence of target sign on DWI and enhancement pattern. Apparent diffusion coefficient (ADC) values were calculated for each lesion ( b = 800 s/mm2). Univariate and multivariate logistic regression analyses were used to identify significant differentiating features between IMCs and SHLMs. Results Univariate analysis revealed that following parameters favor diagnosis of IMCs over SHLMs: lobulating shape, heterogeneous T2W signal intensity, capsular retraction, segmental biliary dilatation, target sign on DWI and rim-like enhancement on arterial phase followed by progressive enhancement in delayed phases. ADC values measured in the periphery of the lesion were significantly lower in IMCs in comparison to SHLMs. Multivariate analysis revealed that target sign on DWI was the most significant predictor of IMCs. Conclusion Qualitative DWI analysis with target sign significantly improves diagnostic accuracy for differentiation among IMC and SHLM lesions.

Quantitative Multiparametric MRI Features and PTEN Expression of Peripheral Zone Prostate Cancer: A Pilot Study

2016 ◽  
Vol 206 (3) ◽  
pp. 559-565 ◽  
Author(s):  
Stephanie M. McCann ◽  
Yulei Jiang ◽  
Xiaobing Fan ◽  
Jianing Wang ◽  
Tatjana Antic ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pilot Study ◽  
Peripheral Zone ◽  
Multiparametric Mri ◽  
Pten Expression ◽  
Mri Features

Defining diagnostic criteria for ductal prostate cancer on prostatic MRI.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17532-e17532
Author(s):  
Weranja Kalana Bodhisiri Ranasinghe ◽  
Patricia Troncoso ◽  
Andrea Kokorovic ◽  
Mohamed A Elsheshtawi ◽  
Miao Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Diagnostic Criteria ◽  
Area Under The Curve ◽  
Prostate Adenocarcinoma ◽  
Accurate Diagnosis ◽  
Sensitivity Analyses ◽  
Nodal Disease ◽  
Mri Features ◽  
Chi Squared ◽  
Adc Values

e17532 Background: Ductal prostate adenocarcinoma (DAC) is an aggressive histologic variant of prostate cancer (PCa) which often be missed due to their low PSA secretion. Further, a large proportion of DACs have extra-prostatic extension and nodal disease at presentation warranting accurate diagnosis and treatment planning. However studies have yet to differentiate DACs from high grade acinar PCas (PAC) on MRI. Therefore we aimed to develop MRI criteria to identify DACs and assess its diagnostic accuracy. Methods: Patients with histologically proven DAC who had MRIs prior to RP were identified from January 2011 to November 2018. Histology-based MRI diagnostic criteria were developed using RP specimens from nine patients with a pure dominant DAC focus and corresponding MRIs. Sixty-eight DAC patients were compared to a matched cohort of 70 patients with Gleason Score 8 or 9 PAC using the pre-defined MRI criteria. Chi-Squared, T tests, Mann Whitney U tests and sensitivity analyses were performed. Results: The following features of DAC were defined on MRI after correlation with histology: 1) intermediate T2 signal 2)well-circumscribed 3) lobulated tumor and 4) a dark peripheral rim. Majority of DACs were lobulated (79.4% vs 5.7%), with a dark peripheral rim on T2 weighted imaging (55.9% vs 4.3%) and had ≥3 MRI features compared to PAC (73.6% vs 7.2%) (all p < 0.001). Moreover, a higher proportion of pure DACs were lobulated (100% vs 5.7%), had a dark peripheral rim (94.7% vs 4.3%) and ≥3 MRI features (100% vs 7.2%) compared to PAC (all P < 0.001). There were no differences in median T2 contrast enhancement, ADC values or ADC ratios between the groups. Using our criteria MRI demonstrated sensitivity of 73.5%, specificity of 92.9 %, PPV of 90.9%, and NPV of 78.3% in diagnosing DACs if ≥3 features were present. In the diagnosis of pure DACs, MRI demonstrated sensitivity of 100%, specificity of 92.9%, PPV of 95.2%, and NPV of 100%. The area under the curve (AUC) for the diagnosis of all DACs was 0.81 and 0.98 for pure DACs. Conclusions: The presence of ≥3 features (well-circumscribed, lobulations and a dark peripheral rim and intermediate signal on the T2 phase) on prostatic MRI can help differentiate DAC from PAC. While this is the largest cohort of DACs to be analyzed, further studies are needed to validate these findings.

Oct1 regulates cell growth of LNCaP cells and is a prognostic factor for prostate cancer

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Hazard Analysis ◽  
Critical Role ◽  
Immunohistochemical Analysis ◽  
Lncap Cells ◽  
Cancer Specific Survival ◽  
High Gleason Score ◽  
Castrate Resistant ◽  
Transcription Factor 1

The androgen receptor (AR) plays a critical role in the development and the progression of prostate cancer. Alterations in theexpression of AR coregulators lead to AR hypersensitivity, which is one of the mechanisms underlying the progression ofprostate cancer into a castrate-resistant state. Octamer transcription factor 1 (Oct1) is a ubiquitous member of the POUhomeodomainfamily that functions as a coregulator of AR. In our study, the contribution of Oct1 to prostate cancerdevelopment was examined. Immunocytochemistry analysis showed that Oct1 is expressed in the nuclei of LNCaP cells.siRNA-mediated silencing of Oct1 expression inhibited LNCaP cell proliferation. Immunohistochemical analysis of Oct1expression in tumor specimens obtained from 102 patients with prostate cancer showed a positive correlation of Oct1immunoreactivity with a high Gleason score and AR immunoreactivity (p 5 0.0042 and p &lt; 0.0001, respectively). Moreover,patients with high immunoreactivity of Oct1 showed a low cancer-specific survival rate, and those patients with highimmunoreactivities of both Oct1 and AR exhibited poorer cancer-specific prognosis. Multivariate hazard analysis revealed asignificant correlation between high Oct1 immunoreactivity and poor cancer-specific survival (p 5 0.012). These resultsdemonstrate that Oct1 can be a prognostic factor in prostate cancer as a coregulator of AR and may lead to the developmentof a new therapeutic intervention for prostate cancer.

scholarly journals Glyoxalase 1 Expression as a Novel Diagnostic Marker of High-Grade Prostatic Intraepithelial Neoplasia in Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3608
Author(s):  
Liliana Rounds ◽  
Ray B. Nagle ◽  
Andrea Muranyi ◽  
Jana Jandova ◽  
Scott Gill ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Diagnostic Marker ◽  
Precancerous Lesion ◽  
Immunohistochemical Analysis ◽  
Intraepithelial Neoplasia ◽  
Prostatic Intraepithelial Neoplasia ◽  
Glycolytic Flux ◽  
Gleason Grade ◽  
High Grade ◽  
Glyoxalase 1

Glyoxalase 1 (GLO1) is an enzyme involved in the detoxification of methylglyoxal (MG), a reactive oncometabolite formed in the context of energy metabolism as a result of high glycolytic flux. Prior clinical evidence has documented GLO1 upregulation in various tumor types including prostate cancer (PCa). However, GLO1 expression has not been explored in the context of PCa progression with a focus on high-grade prostatic intraepithelial neoplasia (HGPIN), a frequent precursor to invasive cancer. Here, we have evaluated GLO1 expression by immunohistochemistry in archival tumor samples from 187 PCa patients (stage 2 and 3). Immunohistochemical analysis revealed GLO1 upregulation during tumor progression, observable in HGPIN and PCa versus normal prostatic tissue. GLO1 upregulation was identified as a novel hallmark of HGPIN lesions, displaying the highest staining intensity in all clinical patient specimens. GLO1 expression correlated with intermediate–high risk Gleason grade but not with patient age, biochemical recurrence, or pathological stage. Our data identify upregulated GLO1 expression as a molecular hallmark of HGPIN lesions detectable by immunohistochemical analysis. Since current pathological assessment of HGPIN status solely depends on morphological features, GLO1 may serve as a novel diagnostic marker that identifies this precancerous lesion.

scholarly journals The triangular fibrocartilage complex on high-resolution 3 T MRI in healthy adolescents: the thin line between asymptomatic findings and pathology

2021 ◽  
Author(s):  
Anne-Sophie van der Post ◽  
Sjoerd Jens ◽  
Frank F. Smithuis ◽  
Miryam C. Obdeijn ◽  
Roelof-Jan Oostra ◽  
...  
Keyword(s):  
Signal Intensity ◽  
Sagittal Plane ◽  
Articular Surface ◽  
Triangular Fibrocartilage Complex ◽  
Ulnar Variance ◽  
Observer Agreement ◽  
Mri Findings ◽  
Mri Features ◽  
Triangular Fibrocartilage ◽  
The Individual

Abstract Objective The objective of the study is to provide a reference for morphology, homogeneity, and signal intensity of triangular fibrocartilage complex (TFCC) and TFCC-related MRI features in adolescents. Materials and methods Prospectively collected data on asymptomatic participants aged 12–18 years, between June 2015 and November 2017, were retrospectively analyzed. A radiograph was performed in all participants to determine skeletal age and ulnar variance. A 3-T MRI followed to assess TFCC components and TFCC-related features. A standardized scoring form, based on MRI definitions used in literature on adults, was used for individual assessment of all participants by four observers. Results per item were expressed as frequencies (percentages) of observations by all observers for all participants combined (n = 92). Inter-observer agreement was determined by the unweighted Fleiss’ kappa with 95% confidence intervals (95% CI). Results The cohort consisted of 23 asymptomatic adolescents (12 girls and 11 boys). Median age was 13.5 years (range 12.0–17.0). Median ulnar variance was −0.7 mm (range − 2.7–1.4). Median triangular fibrocartilage (TFC) thickness was 1.4 mm (range 0.1–2.9). Diffuse increased TFC signal intensity not reaching the articular surface was observed in 30 (33%) observations and a vertical linear increased signal intensity with TFC discontinuation in 19 (20%) observations. Discontinuation between the volar radioulnar ligament and the TFC in the sagittal plane was seen in 23 (25%) observations. The extensor carpi ulnaris was completely dislocated in 10 (11%) observations, more frequent in supinated wrists (p = 0.031). Inter-observer agreement ranged from poor to fair for scoring items on the individual TFCC components. Conclusion MRI findings, whether normal variation or asymptomatic abnormality, can be observed in TFCC and TFCC-related features of asymptomatic adolescents. The rather low inter-observer agreement underscores the challenges in interpreting these small structures on MRI. This should be taken into consideration when interpreting clinical MRIs and deciding upon arthroscopy.

Recent advances in siRNA delivery systems for prostate cancer therapy

2021 ◽  
Vol 22 ◽  
Author(s):  
Shahin Aghamiri ◽  
Pourya Raee ◽  
Shiva Shahmohamadnejad ◽  
Sasan Shabani ◽  
Jaber Ghorbani ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Sirna Delivery ◽  
Delivery Systems ◽  
Multi Drug Resistance ◽  
New Paradigm ◽  
Polymeric Systems ◽  
Chemotherapy Drugs ◽  
Prostate Cancer Therapy ◽  
Effective Delivery ◽  
Critical Problems

: The critical problems of conventional prostate cancer therapeutic strategies like nonspecific toxicity and multi-drug resistance prompted the development and application of countless nanoparticle-based siRNA therapeutics. The main challenges to siRNA-based therapeutics becoming a new paradigm in the treatment of prostate cancer stem from the lack of safe and effective delivery systems, immune system stimulation, poor knowledge of nano-bio interactions, and limitations concerning designing, manufacturing, clinical translation, and commercialization. In this review, we provide cutting-edge advances in nanoparticle-mediated siRNA delivery carriers like polymeric systems, lipid systems, specific systems, and rigid nanoparticles for the treatment of prostate cancer. Moreover, co-delivery of conventional chemotherapy drugs with siRNA as a robust revolutionary strategy for prostate cancer combinational therapy is completely covered.

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