Prostate Cancer SubtyPINg BiomarKers and Outcome: Is Clarity EmERGing?

Smith, Steven C.; Tomlins, Scott A.

doi:10.1158/1078-0432.ccr-14-0818

Cited by 18 publications

(21 citation statements)

References 16 publications

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“…It should be the first time to reveal that both ERG and SPINK1 had relatively low expression frequency in patients with initial diagnosed bone metastatic PCa (10.9% and 13.5%, respectively). Although patients with SPINK1 expression was considered to be lack of ERG rearrangement, apparently and incompletely mutual exclusivity between SPINK1(þ) and ERG(þ) in PCa had been observed, and the co-existence of them was as low as 0.2-4% [14]. But, we did not find any concomitant expression of ERG or SPINK1 in our study.…”

Section: Discussioncontrasting

confidence: 78%

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The expression profile and prognostic value of SPINK1 in initially diagnosed bone metastatic prostate cancer

et al. 2016

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It is the first time to simultaneously detect SPINK1 and ERG expression in initially diagnosed bone metastatic PCa. The over-expression of SPINK1 was not only related to poor PSA response, but also significantly associated with the occurrence of CRPC, especially in those with much more aggressive phenotype (GS 8-10). So, SPINK1 could be considered as a useful prognostic predictor for bone metastatic PCa at the time of diagnosis, and further prospective studies are needed to verify the conclusions. Prostate 76:823-833, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Discussioncontrasting

confidence: 78%

“…To date, a majority of evidence overtly demonstrated that, SPINK1 was almost exclusively allocated in ERG (ETS related gene) negative PCa [14]. However, the prognostic significance of ERG rearrangement in PCa remained controversial [19][20][21][22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

The expression profile and prognostic value of SPINK1 in initially diagnosed bone metastatic prostate cancer

et al. 2016

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“…We also identified a total of 3% of cases with m-ERG + /m-ETS + or m-ERG + /m-SPINK1 + profiles. In our experience, ERG , non- ERG ETS and SPINK1 subtype defining alterations are nearly always mutually exclusive, and observed co-occurrence is most likely due to either misclassification (given the lack of gold standard training data for non-ERG classifiers) or profiling of collisions between genetically distinct tumor clones (which may appear morphologically indistinguishable), although exceptionally rare examples of focal SPINK1 expression in otherwise ERG + tumor have been reported[7,37,38]. As shown by multivariate analysis (Table S8), conflict cases identified herein show similar clinicopathological associations as m-ERG + PCa, consistent with an enrichment of m-ERG + tumors in these conflict cases Thus, studies are ongoing to generate gold standard data for these non-ERG based classifiers.…”

Section: Discussionmentioning

confidence: 99%

Characterization of 1577 Primary Prostate Cancers Reveals Novel Biological and Clinicopathologic Insights into Molecular Subtypes

et al. 2015

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Background Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 over-expression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. Objective To determine the analytical validity and clinicopatholgical associations of microarray-based molecular subtyping. Design, Setting and Participants We analyzed Affymetrix GeneChip expression profiles for 1,577 patients from eight radical prostatectomy (RP) cohorts, including 1,351 cases assessed using the Decipher prognostic assay (performed in a CLIA-certified laboratory). A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS+) or SPINK1 over-expression (SPINK1+). Outcome Measurements Associations with clinical features and outcomes by multivariable logistic regression analysis and receiver operating curves. Results and Limitations The m-ERG classifier showed 95% accuracy in an independent validation subset (n=155 samples). Across cohorts, 45%, 9%, 8% and 38% of PCa were classified as m-ERG+, m-ETS+, m-SPINK1+, and triple negative (m-ERG−/m-ETS−/m-SPINK1−), respectively. Gene expression profiling supports three underlying molecularly defined groups (m-ERG+, m-ETS+ and m-SPINK1+/triple negative). On multivariable analysis, m-ERG+ tumors were associated with lower preoperative serum PSA and Gleason scores, but enriched for extraprostatic extension (p<0.001). m-ETS+ tumors were associated with seminal vesicle invasion (p=0.01), while m-SPINK1+/triple negative tumors had higher Gleason scores and were more frequent in Black/African American patients (p<0.001). Clinical outcomes were not significantly different between subtypes. Conclusions A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes, obviating the need for additional testing. Clinicopathological differences were found among subtypes based on global expression patterns.

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“…Štoviše, SPINK1 posreduje u invaziji unutar stanič-ne linije raka ETS genski negativnih karcinoma prostate. Mehanizam SPINK1 ekspresije za ovu podskupinu ostaje za istraživanje i nije objašnjen kromosomskim preuređivanjem, delecijom ili amplifikacijom gena 44,45 .…”

Section: Erg Protein I Ptenunclassified

Pathohistological diagnosis of prostate cancer

2017

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Sažetak. Rak prostate najčešći je malignom u muškaraca u Europi i SAD-u, raznolik u kliničkoj prezentaciji, patohistološkoj slici, obrascima rasta i širenja. Kada se rak prostate otkrije u ranom stadiju postotak izlječenja je visok. Definitivna verifikacija je patohistološka s individualnom procjenom agresivnog potencijala tumora kroz prognostičke parametre kao što su Gleasonov gradus/gradusna skupina, postotak i broj zahvaćenih cilindara tumorom u iglenoj biopsiji, stadij i pozitivan rub kod prostatektomije. Ovi čimbenici danas značajno utječu na izbor i protokole terapija, ali u ranom stadiju ne mogu prepoznati lokalizirani, klinički značajan karcinom koji će sigurno izazvati metastatku bolest te zahtijeva liječenje. Stoga su se istraživanja danas usredotočila na molekularne biomarkere koji su važni u prognozi, patogenezi te kao ciljne molekule za moguću terapiju. Članak pridonosi boljem razumijevanju patohistološkog nalaza i novih činjenica u molekularnoj patogenezi tumora, što je važno za zbrinjavanje pacijenata s rakom prostate.Ključne riječi: karcinom prostate; molekularni biomarkeri; prognostički čimbenici Abstract. Prostate cancer (PCa) is the most common male cancer in Europe and the US. The early diagnosis relies on prostate specific antigen serum test, digito-rectal and ultrasound exmination. Definitive verification is pathohistological with individual assesment of aggressiveness of the tumor potential through prognostic parameters such as Gleason gradus/grade groups, percentage and number of affected cilinders in the biopsy, stage and positive margins in prostatectomy. These parameters significantly affect the choice and protocol of therapies but can not identify a localized, clinically significant cancer that will certainly cause metastatic disease and require treatment. Therefore, researchers focused on molecular biomarkers that are important in prognosis, pathogenesis, and as a target molecules for possible therapy. The article contributes to a better understanding of the pathohistological findings and new facts about the molecular pathogenesis of tumors, which are important for the care of patients with prostate cancer.

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Prostate Cancer SubtyPINg BiomarKers and Outcome: Is Clarity EmERGing?

Cited by 18 publications

References 16 publications

The expression profile and prognostic value of SPINK1 in initially diagnosed bone metastatic prostate cancer

The expression profile and prognostic value of SPINK1 in initially diagnosed bone metastatic prostate cancer

Characterization of 1577 Primary Prostate Cancers Reveals Novel Biological and Clinicopathologic Insights into Molecular Subtypes

Pathohistological diagnosis of prostate cancer

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