Systems Pathology Approach for the Prediction of Prostate Cancer Progression After Radical Prostatectomy

Donovan, Michael; Hamann, Stefan; Clayton, M.; Khan, Faisal; Sapir, Marina; Bayer-Zubek, Valentina; Fernández, Gerardo; Mesa-Tejada, Ricardo; Teverovskiy, Mikhail; Reuter, Victor E.; Scardino, Peter T.; Cordon‐Cardo, Carlos

doi:10.1200/jco.2007.15.3155

Cited by 83 publications

(92 citation statements)

References 28 publications

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“…Several new molecular markers, including early prostate cancer antigen (EPCA-2), the PCA3 urine test, TMPRSS2:ERG gene fusions, and androgen receptor content, appear promising in identifying indolent tumors [23][24][25][26], but at present, their ability to add additional predictive value above that contained in the clinical parameters (tumor volume, grade, stage, and PSA) on which the Epstein criteria are based is limited [27].…”

Section: Discussionmentioning

confidence: 99%

The Epstein Criteria Predict for Organ-Confined But Not Insignificant Disease and a High Likelihood of Cure at Radical Prostatectomy

et al. 2010

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Section: Discussionmentioning

confidence: 99%

The Epstein Criteria Predict for Organ-Confined But Not Insignificant Disease and a High Likelihood of Cure at Radical Prostatectomy

et al. 2010

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“…High expression levels of the AR protein in patients treated with radical prostatectomy before ADT have been associated with worse overall and disease-specific survival and shorter time to disease relapse (reviewed in Donovan et al (2008Donovan et al ( , 2010 and Hodgson et al (2012)). We showed a similar finding for patients with locally obstructive HN PC treated by palliative TURP.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor β expression and androgen receptor phosphorylation correlate with a poor clinical outcome in hormone-naïve prostate cancer and are elevated in castration-resistant disease

Zellweger¹,

Stürm²,

Rey³

et al. 2013

Endocrine-Related Cancer

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“…Additionally, to our knowledge, no AURKA SNPs have been reported in any prostate cancer genome wide association studies. Further studies are necessary given the prognostic utility of SNPs in predicting cancer risk and recurrence [11,12], based on the premise that these SNP studies will enhance the accuracy of existing prognostic nomograms that incorporate clinical variables such as clinical stage, Gleason score, and prostate-specific antigen (PSA) levels [13].…”

Section: Introductionmentioning

confidence: 99%

The Aurora Kinase A Polymorphisms are not Associated with Recurrence-free Survival in Prostate Cancer Patients

Jaboin

Ausborn

Hwang

et al. 2012

JCST

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Background: The purpose of this study was to investigate the association between haplotype-tagging single nucleotide polymorphisms (SNPs) within the Aurora Kinase A (AURKA) gene and prostate cancer outcomes in patients with clinically localized prostate cancer. Methods:Four intronic haplotype-tagging SNPs within the AURKA gene were individually selected and examined in regard to their influence on clinical outcomes in 212 patients who underwent radical prostatectomy as first-line treatment. Haplotype-tagging SNPs were selected using the ABI SNP Browser to cover SNPs with an r 2 of 0.90 or greater in the AURKA gene with a minor allele frequency of at least 0.25. Results:In our study, a log-rank univariate analysis was performed to identify significant associations between probability of recurrence-free survival or disease-free survival and known prognostic indicators as well as AURKA genotypes. The prognostic indicators Gleason grade, surgical margin, extracapsular extension, and disease stage were associated with recurrence-free survival (all p<0.001). Only Gleason grade was associated with disease-free survival (p<0.001). No associations were found for the SNPs rs1468055, rs8117896, rs2064863, and rs1468056 analyzed for either RFS (p=0.7213, p=0.5140, p=0.0714, p=0.4731, respectively) or DFS (p=0.3282, p=0.1909, p=0.4111, p=0.5014, respectively). Clinical data on patient follow-up at Vanderbilt University Medical Center were retrospectively gathered via electronic medical records. The mean follow-up for disease-free survival and assessment of prostate cancer progression were 8.3 ± 2.4-y and 4.4 ± 3.9-y, respectively. The endpoints analyzed were recurrence-free survival (RFS) and diseasefree survival (DFS). Recurrence post-prostatectomy was classified as biochemical (which has been shown to be a poor predictor of overall survival in patients with localized prostate cancer treated with radical prostatectomy) [14], local or distant, and the most advanced recurrence type documented was assigned to each patient. Biochemical recurrence was defined as a prostate-specific antigen (PSA) detection of > 0.1 ng/ ml in at least two consecutive tests. DFS was defined as the length of time between the date of prostatectomy to the date of death or last follow-up. Conclusions Genotyping of Aurora Kinase A polymorphisms in prostate cancer samplesProstatectomy specimens were processed and genomic DNA extracted from deparaffinizedspecimens as described previously [15]. Purified genomic DNA was genotyped for the following haplotypetagging SNPs in the AURKA gene: rs1468055, rs8117896, rs2064863, and rs1468056. Haplotype-tagging SNPs (htSNPs) were selected using the ABI SNP Browser to cover SNPs with an r 2 of 0.90 or greater in the AURKA gene with a minor allele frequency (MAF) of at least 0.25. A total of 4 SNPs were selected and genotyped in our patient cohort. Allelic discrimination of these AURKA polymorphisms was performed using Taqman SNP genotyping assays (Applied Biosystems: and C_8947664_10 [rs1468056]). The fina...

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Systems Pathology Approach for the Prediction of Prostate Cancer Progression After Radical Prostatectomy

Abstract: The integration of clinicopathologic variables with imaging and biomarker data (systems pathology) resulted in a highly accurate tool for predicting CF within 5 years after prostatectomy. The data support a role for AR signaling in clinical progression and duration of response to ADT.

Cited by 83 publications

References 28 publications

The Epstein Criteria Predict for Organ-Confined But Not Insignificant Disease and a High Likelihood of Cure at Radical Prostatectomy

The Epstein Criteria Predict for Organ-Confined But Not Insignificant Disease and a High Likelihood of Cure at Radical Prostatectomy

Estrogen receptor β expression and androgen receptor phosphorylation correlate with a poor clinical outcome in hormone-naïve prostate cancer and are elevated in castration-resistant disease

The Aurora Kinase A Polymorphisms are not Associated with Recurrence-free Survival in Prostate Cancer Patients

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