ERG Overexpression and PTEN Status Predict Capsular Penetration in Prostate Carcinoma

Nagle, Raymond B.; Algotar, Amit M.; Cortez, Connie C.; Smith, Katherine J.; Jones, Carol; Yun, Steven; Riley, Janice; Nagy, Dea; Dittamore, Ryan; Dalkin, Bruce L.; Brosh, Laura; Pestano, Gary A.

doi:10.1002/pros.22675

Cited by 17 publications

(14 citation statements)

References 33 publications

(40 reference statements)

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“…Prior studies have reported that the lack of ETS gene fusions and lack of PTEN loss ( ERG wt/ PTEN wt) were associated with good prognosis in patients undergoing radical prostatectomy or in a conservatively treated watchful waiting cohort (39–41). However those who were ERG +/ PTEN del had faster BCR rates in the prostatectomy cohort (41), whereas the ERG wt/ PTEN del patients had significantly lower survival rates than ERG +/ PTEN del patients in the watchful waiting cohort (31).…”

Section: Discussionmentioning

confidence: 99%

Recurrent Prostate Cancer Genomic Alterations Predict Response to Brachytherapy Treatment

Fontugne

Lee

Cantaloni

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background This study aimed to evaluate the association of recurrent molecular alterations in prostate cancer, such as ERG rearrangements and phosphatase and tensin homolog gene (PTEN) deletions, with oncologic outcomes in patients with prostate cancer treated with brachytherapy. Methods Ninety-two men underwent I-125 brachytherapy with a 145 Gy delivered dose between 2000 and 2008. Pretreatment prostate biopsies were analyzed by immunohistochemistry (IHC) and FISH for ERG rearrangement and overexpression, PTEN deletion, and expression loss. Univariable and multivariable Cox-regression analyses evaluated association of ERG and PTEN status with biochemical recurrence (BCR). Results Within a median follow-up of 73 months, 11% of patients experienced BCR. Of 80 samples with both IHC and FISH performed for ERG, 46 (57.8%) demonstrated rearrangement by FISH and 45 (56.3%) by IHC. Of 77 samples with both IHC and FISH for PTEN, 14 (18.2%) had PTEN deletion by FISH and 22 (28.6%) by IHC. No significant associations were found between ERG, PTEN status, and clinicopathologic features. Patients with concurrent ERG rearrangement and PTEN deletion demonstrated significantly worse relapse-free survival rates compared with those with ERG or PTEN wild type (P < 0.01). In multivariable Cox regression analysis adjusted for the effects of standard clinicopathologic features, combined ERG rearranged and PTEN deletion was independently associated with BCR (HR = 2.6; P = 0.02). Conclusions Concurrent ERG rearrangement and PTEN loss was independently associated with time to BCR in patients undergoing brachytherapy. Future studies are needed to validate prostate cancer molecular subtyping for risk stratification. Impact Identifying patients in the ERG-rearranged/PTEN-deleted molecular subclass may improve treatment personalization.

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Section: Discussionmentioning

confidence: 99%

Recurrent Prostate Cancer Genomic Alterations Predict Response to Brachytherapy Treatment

Fontugne

Lee

Cantaloni

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Further, the multifocal nature of prostate cancer is well- recognized and several studies have documented the interfocal heterogeneity of ERG rearrangements in PCa harboring multiple tumor foci[11],[12] [13]. Hence genetically distinct tumor foci within the same patient are not unusual.…”

Section: Introductionmentioning

confidence: 99%

Novel RNA Hybridization Method for the In Situ Detection of ETV1, ETV4, and ETV5 Gene Fusions in Prostate Cancer

Kunju

Carskadon

Siddiqui

et al. 2014

Applied Immunohistochemistry &Amp; Molecular Morphology

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The genetic basis of 50–60% of prostate cancer is attributable to rearrangements in ETS (ERG, ETV1, ETV4, and ETV5), BRAF and RAF1 genes and overexpression of SPINK1. The development and validation of reliable detection methods are warranted to classify various molecular subtypes of prostate cancer for diagnostic and prognostic purposes. ETS gene rearrangements are typically detected by fluorescence in situ hybridization (FISH) and reverse transcription PCR methods. Recently, monoclonal antibodies against ERG have been developed that detect the truncated ERG protein in immunohistochemical assays where staining levels are strongly correlated with ERG rearrangement status by FISH. However, specific antibodies for ETV1, ETV4 and ETV5 are unavailable, challenging their clinical use. We developed a novel RNA in situ hybridization based assay for the in situ detection of ETV1, ETV4, and ETV5 in formalin fixed paraffin embedded tissues from prostate needle biopsies, prostatectomy, and metastatic prostate cancer specimens using RNA probes. Further, with combined RNA in situ hybridization and immunohistochemistry we identified a rare subset of prostate cancer with dual ETS gene rearrangements in collisions of independent tumor foci. The high specificity and sensitivity of RNA in situ hybridization provides an alternate method enabling bright field in situ detection of ETS gene aberrations in routine clinically available prostate cancer specimens.

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“…Prostate cancer (PCa) is also known to express variable levels of several markers associated with disease progression, such as phosphatase tensin homolog (PTEN) and ETS-Related Gene (ERG), making it a viable target for testing this procedure. A link between the PTEN pathway and ERG protein expression has previously been evaluated in various prostate cancer studies [8][9][10][11][12][13]. In studies investigating the trend of PTEN loss in tumors of prostatectomies and locally recurring castrate-resistant prostate cancers (CRCPs) with ERG overexpression, the data showed that the loss of PTEN was significantly associated with ERG positivity [11].…”

Section: Experimental Designmentioning

confidence: 99%

A Method to Reuse Archived H&E Stained Histology Slides for a Multiplex Protein Biomarker Analysis

Hinton

Dvorak

Roberts

et al. 2019

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Archived Hematoxylin and Eosin (H&E) stained pathology slides are routinely stored to index formalin-fixed paraffin-embedded (FFPE) sample tissue blocks. FFPE blocks are clinically annotated human tumor specimens that can be valuable in studies decades after the tissue is collected. If stored properly, they have the potential to yield a valuable number of serial sectioned slides for diagnostic or research purposes. However, some retrospective studies are limited in scope because the tissue samples have been depleted or not enough material is available in stored blocks for serial sections. The goal of these studies was to determine if archived H&E-stained slides can be directly reutilized by optimizing methods to de-stain and then re-stain the H&E stained slides to allow the detection of several biomarkers of interest using a conjugated antibody with chromogen multiplex immunohistochemistry procedure. This simple but innovative procedure, combined with image analysis techniques, demonstrates the ability to perform precise detection of relevant markers correlated to disease progression in initially identified tumor regions in tissue. This may add clinical value in retaining H&E slides for further use.

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ERG Overexpression and PTEN Status Predict Capsular Penetration in Prostate Carcinoma

Cited by 17 publications

References 33 publications

Recurrent Prostate Cancer Genomic Alterations Predict Response to Brachytherapy Treatment

Recurrent Prostate Cancer Genomic Alterations Predict Response to Brachytherapy Treatment

Novel RNA Hybridization Method for the In Situ Detection of ETV1, ETV4, and ETV5 Gene Fusions in Prostate Cancer

A Method to Reuse Archived H&E Stained Histology Slides for a Multiplex Protein Biomarker Analysis

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