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DNA repair deregulation in discrete prostate cancer lesions identified on multi-parametric MRI and targeted by MRI/ultrasound fusion-guided biopsy.

ABSTRACT: Prostate cancer is histologically and molecularly heterogeneous. Clinically significant disease is often driven by dominant intra-prostatic lesions (IPLs). Prostate cancers cluster into molecular phenotypes with substantial genetic heterogeneity making pathway-based molecular analysis appealing. MRI/ultrasound fusion biopsy provides a unique opportunity to characterize tumor biology of discrete lesions at diagnosis. This study determined the feasibility of pathway-based gene expression analysis of prostate biopsies and characterized cancer pathway deregulation. Thirteen patients had prostate cancer diagnosed by MRI/ultrasound fusion biopsy and either Gleason 6 or Gleason ≥8. Gene expression profiling was performed on 14 biopsies using >700 genes representing 13 cancer pathways. Pathway-based analysis compared gene expression among samples based on clinical, pathological, and radiographic characteristics. Pathway-based gene expression analysis was successful in 12 of 14 (86%) samples. Samples clustered based upon deregulation of DNA Repair and Notch, Chromatin Modification and Cell Cycle, or all other pathways, respectively. DNA Repair demonstrated the greatest differential deregulation. Lesions with Gleason ≥8, PSA ≥10, or intense dynamic contrast enhancement (DCE) had significantly higher DNA Repair deregulation than those with Gleason 6, PSA <10, or low to moderate DCE. Alterations in DNA Repair gene expression were diverse with upregulation of markers of DNA damage and down-regulation of DNA Repair proteins. This study demonstrates the feasibility of pathway-level gene expression analysis of discrete intra-prostatic lesions sampled by MRI/ultrasound fusion biopsy. IPLs cluster into distinct molecular phenotypes, the most significantly altered being DNA Repair.

SUBMITTER: Dulaney CR

PROVIDER: S-EPMC5620234 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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DNA repair deregulation in discrete prostate cancer lesions identified on multi-parametric MRI and targeted by MRI/ultrasound fusion-guided biopsy.

Dulaney Caleb R CR Rais-Bahrami Soroush S Manna Debra Della DD Gordetsky Jennifer B JB Nix Jeffrey W JW Yang Eddy S ES

Oncotarget 20170710 40

Prostate cancer is histologically and molecularly heterogeneous. Clinically significant disease is often driven by dominant intra-prostatic lesions (IPLs). Prostate cancers cluster into molecular phenotypes with substantial genetic heterogeneity making pathway-based molecular analysis appealing. MRI/ultrasound fusion biopsy provides a unique opportunity to characterize tumor biology of discrete lesions at diagnosis. This study determined the feasibility of pathway-based gene expression analysis ...[more]

PMID: 28978094

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Project description:To determine the evolution of prostatic multi-parametric magnetic resonance imaging (mp-MRI) signal following transrectal ultrasound (TRUS)-guided biopsy.Local ethical permission and informed written consent was obtained from all the participants (n=14, aged 43-69, mean 64 years). Patients with a clinical suspicion of prostate cancer (PSA range 2.2-11.7, mean 6.2) and a negative (PIRAD 1-2/5) pre-biopsy mp-MRI (pre-contrast T1, T2, diffusion-weighted and dynamic-contrast-enhanced MRI) who underwent 10-core TRUS-guided biopsy were recruited for additional mp-MRI examinations performed at 1, 2 and 6 months post biopsy. We quantified mp-MRI peripheral zone (PZ) and transition zone (TZ) normalized T2 signal intensity (nT2-SI); T1 relaxation time (T10); diffusion-weighted MRI, apparent diffusion coefficient (ADC); dynamic contrast-enhanced MRI, maximum enhancement (ME); slope of enhancement (SoE) and area-under-the-contrast-enhancement-curve at 120 s (AUC120). Significant changes in mp-MRI parameters were identified by analysis of variance with Dunnett's post testing.Diffuse signal changes were observed post-biopsy throughout the PZ. No significant signal change occurred following biopsy within the TZ. Left and right PZ mean nT2-SI (left PZ: 5.73, 5.16, 4.90 and 5.12; right PZ: 5.80, 5.10, 4.84 and 5.05 at pre-biopsy, 1, 2 and 6 months post biopsy, respectively) and mean T10 (left PZ: 1.02, 0.67, 0.78, 0.85; right PZ: 1.29, 0.64, 0.78, 0.87 at pre-biopsy, 1, 2 and 6 months post biopsy, respectively) were reduced significantly (P<0.05) from pre-biopsy values for up to 6 months post biopsy. Significant changes (P<0.05) of PZ-ME and AUC120 were observed at 1 month but resolved by 2 months post biopsy. PZ ADC did not change significantly following biopsy (P=0.23-1.0). There was no significant change of any TZ mp-MRI parameter at any time point following biopsy (P=0.1-1.0).Significant PZ (but not TZ) T2 signal changes persist up to 6 months post biopsy, whereas PZ and TZ ADC is not significantly altered as early as 1 month post biopsy. Caution must be exercised when interpreting T1- and T2-weighted imaging early post biopsy, whereas ADC images are more likely to maintain clinical efficacy.

Project description:ImportanceTargeted magnetic resonance (MR)/ultrasound fusion prostate biopsy has been shown to detect prostate cancer. The implications of targeted biopsy alone vs standard extended-sextant biopsy or the 2 modalities combined are not well understood.ObjectiveTo assess targeted vs standard biopsy and the 2 approaches combined for the diagnosis of intermediate- to high-risk prostate cancer.Design, setting, and participantsProspective cohort study of 1003 men undergoing both targeted and standard biopsy concurrently from 2007 through 2014 at the National Cancer Institute in the United States. Patients were referred for elevated level of prostate-specific antigen (PSA) or abnormal digital rectal examination results, often with prior negative biopsy results. Risk categorization was compared among targeted and standard biopsy and, when available, whole-gland pathology after prostatectomy as the "gold standard."InterventionsPatients underwent multiparametric prostate magnetic resonance imaging to identify regions of prostate cancer suspicion followed by targeted MR/ultrasound fusion biopsy and concurrent standard biopsy.Main outcomes and measuresThe primary objective was to compare targeted and standard biopsy approaches for detection of high-risk prostate cancer (Gleason score ≥ 4 + 3); secondary end points focused on detection of low-risk prostate cancer (Gleason score 3 + 3 or low-volume 3 + 4) and the biopsy ability to predict whole-gland pathology at prostatectomy.ResultsTargeted MR/ultrasound fusion biopsy diagnosed 461 prostate cancer cases, and standard biopsy diagnosed 469 cases. There was exact agreement between targeted and standard biopsy in 690 men (69%) undergoing biopsy. Targeted biopsy diagnosed 30% more high-risk cancers vs standard biopsy (173 vs 122 cases, P < .001) and 17% fewer low-risk cancers (213 vs 258 cases, P < .001). When standard biopsy cores were combined with the targeted approach, an additional 103 cases (22%) of mostly low-risk prostate cancer were diagnosed (83% low risk, 12% intermediate risk, and 5% high risk). The predictive ability of targeted biopsy for differentiating low-risk from intermediate- and high-risk disease in 170 men with whole-gland pathology after prostatectomy was greater than that of standard biopsy or the 2 approaches combined (area under the curve, 0.73, 0.59, and 0.67, respectively; P < .05 for all comparisons).Conclusions and relevanceAmong men undergoing biopsy for suspected prostate cancer, targeted MR/ultrasound fusion biopsy, compared with standard extended-sextant ultrasound-guided biopsy, was associated with increased detection of high-risk prostate cancer and decreased detection of low-risk prostate cancer. Future studies will be needed to assess the ultimate clinical implications of targeted biopsy.Trial registrationclinicaltrials.gov Identifier: NCT00102544.

Project description:BackgroundTo investigate puncture skills and complications prevention in ultrasound-guided percutaneous needle biopsy for peripheral lung lesions.MethodsNinety-two peripheral lung lesions in 92 patients, detected via computed tomography (CT) and also visible on ultrasound, were retrospectively analyzed. All patients underwent percutaneous peripheral lung lesion needle biopsy under traditional ultrasound or contrast enhanced ultrasound (CEUS) guidance paying attention to avoiding necrotic areas and large blood vessels. All the specimens were examined histopathologically. Preprocedure all 92 lesions were performed by traditional ultrasonography to evaluate the size, the echogenecity, liquefaction areas and blood flow on color Doppler imaging, some of which were performed by CEUS for evaluating non-enhanced necrosis areas, contrast agent arrival time (AT) and characteristics of blood perfusion.ResultsThe histopathologic results of all 92 lesions were as follows: 67 malignant tumors (including 28 adenocarcinomas, 19 squamous cell carcinomas, 6 bronchoalveolar carcinomas, 5 small cell carcinomas, 5 metastatic cancers, 3 poorly differentiated cancers and 1 malignant mesothelioma), 20 benign lesions (including 9 pneumonia, 6 inflammatory pseudotumors and 5 tuberculomas), 5 undetermined lesions. Of 52 lesions by CEUS guidance, 7 lesions showed enhancement in the pulmonary arterial-phase (including 6 pneumonia and 1 malignant tumors), 45 lesions showed enhancement in the bronchial artery phase (including 37 malignant tumors, 3 inflammatory pseudotumors, 4 tuberculomas and 1 undetermined lesion). According to needle insertion angle along linear path, a total of 92 lesions were divided into two groups, 49 lesions at an angle of 70°-80° needle insertion and 43 lesions at an angle of 80°-90° needle insertion. In the study, linear and non-linear two puncture paths were used, we first tried to puncture along linear path in all lesions, if an attempt to insert into the lesions failed due to be blocked by the ribs and then changed to puncture along non-linear path instead. The success rate of biopsy procedure along linear puncture was significantly higher at an angle of 80°-90°group (93.0% vs. 20.4%, P<0.01), and the adoption rate of non-linear path biopsy for solving the puncture needle blocked by the ribs was significantly higher at angle of 70°-80°group (79.6% vs. 7.0%, P<0.01). Of 52 lesions by CEUS guidance, 27 (51.9%) showed non enhanced necrosis areas on CEUS, only 5 showed liquefaction necrosis areas on gray-scale ultrasound. Of 40 lesions by traditional ultrasound guidance, 4 showed necrosis areas on gray-scale ultrasound. There were no significant differences in lesion size, the average number of biopsy attempts and complication rates between CEUS guidance group and traditional ultrasound guidance group (P>0.05), the pathological confirmation rate in CEUS guidance group was higher than that in traditional ultrasound guidance group, but without significant difference (98.1% vs. 90.0%, P>0.05). Of all 92 cases, 3 cases (3.3%) had mild pneumothorax and 4 cases (4.3%) had hemoptysis.ConclusionsIn ultrasound-guided needle biopsy for peripheral lung lesions, using a combination of linear and non-linear puncture techniques and keeping away from necrotic areas and large blood vessels, may help to increase the success rate and reduce the incidence of complications further.

Dataset Information

DNA repair deregulation in discrete prostate cancer lesions identified on multi-parametric MRI and targeted by MRI/ultrasound fusion-guided biopsy.

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DNA repair deregulation in discrete prostate cancer lesions identified on multi-parametric MRI and targeted by MRI/ultrasound fusion-guided biopsy.

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