<i>PTEN</i> Expression in Prostate Cancer: Relationship With Clinicopathologic Features and Multiparametric MRI Findings

Switlyk, Marta D.; Salberg, Unn Beate; Geier, Oliver; Vlatkovic, Ljiljana; Lilleby, Wolfgang; Lyng, Heidi; Seierstad, Therese

doi:10.2214/ajr.18.20743

Cited by 17 publications

(23 citation statements)

References 44 publications

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“…However, even when Gleason grade was controlled for, PTEN loss remained higher in the targeted biopsy group. A similar association between PTEN loss and ADC values was demonstrated in a radical prostatectomy population; however, no correlation between PTEN expression and Gleason grade was shown [43] . Other studies found an association with Gleason score ( r = − 0.30, p = 0.04) and K ep ( r = − 0.35, p = 0.02) but not with ADC [44] .…”

Section: Evidence Synthesissupporting

confidence: 60%

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

Norris

Simpson

Parry

et al. 2020

European Urology Open Science

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Context Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain. Objective To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study. Evidence acquisition We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment. Evidence synthesis We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue ( PTEN ) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours. Conclusions Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets. Patient summary Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility.

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Section: Evidence Synthesissupporting

confidence: 60%

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

Norris

Simpson

Parry

et al. 2020

European Urology Open Science

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“…MRI is considered the most sensitive and specific imaging technique for localizing and staging clinically significant PCa. In our patient, the pretreatment imaging findings, including low apparent diffusion coefficient (ADC) values within the tumor, were consistent with the features of aggressive PCa and are in agreement with previous reports [ 47 ].…”

Section: Discussionsupporting

confidence: 92%

The Quandary of DNA-Based Treatment Assessment in De Novo Metastatic Prostate Cancer in the Era of Precision Oncology

Nakken

Lilleby

Switlyk

et al. 2021

JPM

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Guidelines for genetic testing have been established for multiple tumor types, frequently indicating the most confident molecularly targeted treatment options. However, considering the often-complex presentation of individual cancer patients, in addition to the combinatorial complexity and inherent uncertainties of molecular findings, deriving optimal treatment strategies frequently becomes very challenging. Here, we report a comprehensive analysis of a 68-year-old male with metastatic prostate cancer, encompassing pathology and MRI findings, transcriptomic results, and key genomics findings from whole-exome sequencing, both somatic aberrations and germline variants. We identify multiple somatic aberrations that are known to be enriched in prostate cancer, including a deletion of PTEN and a fusion transcript involving BRCA2. The gene expression patterns in the tumor biopsy were also strikingly similar to prostate tumor samples from TCGA. Furthermore, we detected multiple lines of evidence for homologous recombination repair deficiency (HRD), including a dominant contribution by mutational signature SBS3, which is specifically attributed to HRD. On the basis of the genomic and transcriptomic findings, and in light of the clinical case presentation, we discussed the personalized treatment options that exist for this patient and the various challenges that one faces in the process of translating high-throughput sequencing data towards treatment regimens.

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“…McCann et al demonstrated that ADC mean and ADC 10% (tenth percentile ADC) are probably not associated with PTEN-efficiency PCa, as shown by immunohistochemistry (8). On the other hand, Switlyk et al argued that ADC derived from DWI may be useful in selecting patients with potentially aggressive tumor caused by PTEN loss, using bead arrays and reverse-transcription quantitative polymerase chain reaction analysis (9). In our sample set, ADC mean played only a minor role in differentiation between PTEN-deficiency tumor and PTEN-intact tumor, unlike Switlyk et al and in accord with the view of McCann et al A possible explanation accounting for the differences is in the methods for detection of molecular aberrations.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have been performed to determine tumor aggressiveness by means of mpMRI, demonstrating a significant correlation between quantitative MRI parameters such as apparent diffusion coefficient (ADC) and Gleason score (7). The association between PTEN deficiency and ADC has also been investigated by several groups (8,9). However, they were not identical in views.…”

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confidence: 99%

Diagnostic Value of⁶⁸Ga-PSMA PET/CT for Detection of Phosphatase and Tensin Homolog Expression in Prostate Cancer: A Pilot Study

et al. 2019

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Our purpose was to explore the value of 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT for detection of phosphatase and tensin homolog (PTEN)-loss prostate cancer. Methods: We retrospectively enrolled 75 patients who underwent multiparametric MRI and 68 Ga-PSMA PET/CT before radical prostatectomy. Lesions were outlined on pathologic images, and regions of interest were drawn on matched multiparametric MRI and PET/CT images. Imaging parameters, including average apparent diffusion coefficient and SUV max , were derived. Immunohistochemical staining was performed to evaluate the PTEN status. The diagnostic performance of imaging parameters was analyzed by receiver-operating-characteristic analysis. Univariate logistic regression analyses were used to evaluate the association between clinical and imaging variables and PTEN status. Results: In total, 103 lesions from 75 patients were analyzed. Of these lesions, 38 of 103 (36.9%) showed PTEN-loss status. Our study showed a strong association between SUV max and PTEN-loss tumors both in the per-patient analysis (P , 0.01) and in the per-lesion analysis (P , 0.01), yielding sensitivity and specificity of 0.80 and 0.77, respectively, in the perpatient analysis and 0.83 and 0.74, respectively, in the per-lesion analysis. Meanwhile, higher pathologic PSMA expression was found in the PTEN-deficiency tumors. However, there was no significant difference between PTEN-loss tumors and PTEN-intact tumors using parameters such as average apparent diffusion coefficient (P. 0.05) and score on the Prostate Imaging Reporting and Data System, version 2 (P. 0.05). Surprisingly, SUV max was a significant predictor for detection of PTENloss tumors (odds ratio of 7.56 and 95% confidence interval of 2.18-26.24 on per-patient analysis; odds ratio of 13.66 and 95% confidence interval of 4.32-43.24 on per-lesion analysis). Conclusion: 68 Ga-PSMA PET/CT could effectively detect aggressive PTEN-loss tumors.

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PTEN Expression in Prostate Cancer: Relationship With Clinicopathologic Features and Multiparametric MRI Findings

Cited by 17 publications

References 44 publications

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

The Quandary of DNA-Based Treatment Assessment in De Novo Metastatic Prostate Cancer in the Era of Precision Oncology

Diagnostic Value of⁶⁸Ga-PSMA PET/CT for Detection of Phosphatase and Tensin Homolog Expression in Prostate Cancer: A Pilot Study

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PTEN Expression in Prostate Cancer: Relationship With Clinicopathologic Features and Multiparametric MRI Findings

Cited by 17 publications

References 44 publications

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

The Quandary of DNA-Based Treatment Assessment in De Novo Metastatic Prostate Cancer in the Era of Precision Oncology

Diagnostic Value of68Ga-PSMA PET/CT for Detection of Phosphatase and Tensin Homolog Expression in Prostate Cancer: A Pilot Study

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Diagnostic Value of⁶⁸Ga-PSMA PET/CT for Detection of Phosphatase and Tensin Homolog Expression in Prostate Cancer: A Pilot Study