Use of TMPRSS2-ERG gene rearrangement and quantitative ERG expression to predict clinical recurrence after radical prostatectomy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 36-36
Author(s):  
E. A. Klein ◽  
S. M. Falzarano ◽  
T. Maddala ◽  
D. Cherbavaz ◽  
W. F. Novotny ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Clinical Data ◽  
Gene Rearrangement ◽  
Clinical Stage ◽  
Clinical Recurrence ◽  
Psa Recurrence ◽  
Stage T1

36 Background: The association of TMPRSS2-ERG fusions and ERG expression in prostate cancer (PC) with adverse clinical outcomes has been controversial, with mixed results in the literature. We conducted a study to test whether tumor-derived gene expression profiles, including the presence of TMPRSS2-ERG fusions and ERG gene expression, are associated with clinical recurrence (cR) after radical prostatectomy (RP). Methods: All patients with clinical stage T1/T2 prostate cancer treated with RP at CC from 1987 to 2004 were identified (n∼f2,600). A cohort sampling design was used to select 127 patients with cR and 374 patients without cR after RP. For each patient a primary Gleason pattern (GP) sample, secondary (or highest) GP sample, and an adjacent nontumor tissue sample were evaluated. Surgical Gleason Score (GS) and clinical data were centrally reviewed. RNA was extracted from 6 manually dissected 10 μ m formalin-fixed paraffin-embedded sections obtained from RP specimens and expression of TMPRSS2-ERGa, TMPRSS2-ERGb, ERG and reference genes were quantified using RT-PCR. Times to cR, PSA recurrence, and PC death were analyzed using Cox PH regression. Results: Blocks from 441 patients were evaluable. Median F/U was 5.8 years. Patients were mostly Caucasian (83%), clinical stage T1 (66%), had baseline PSA <10 ng/mL (82%), and had surgical Gleason score ≤7 (87%). 848 tumor samples and 410 non-tumor samples were assessed. TMPRSS2-ERGa and/or TMPRSS2-ERGb fusions were present in 51.8% of tumor samples and 7.5% of non-tumor samples. There was 89% concordance (95% CI: 86%, 92%) for TMPRSS2-ERG fusion status between the 2 tumor samples for each patient. High ERG expression was strongly associated with the presence of TMPRSS2-ERG fusions (p <0.01). We did not find an association between TMPRSS2-ERG a/b gene rearrangement or ERG expression with cR, PSA recurrence, PC death, or surgical GS (p > 0.2). Conclusions: This study was notable for the large number of cR events, use of a standardized quantitative assay, and rigorous central review of pathology and clinical data. We did not find an association of TMPRSS2-ERG gene rearrangements or ERG expression with aggressiveness of prostate cancer post RP. [Table: see text]

Use of quantitative gene expression in primary and highest Gleason pattern cancers to identify genes associated with clinical recurrence after radical prostatectomy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 39-39 ◽  
Author(s):  
E. A. Klein ◽  
S. M. Falzarano ◽  
T. Maddala ◽  
C. Millward ◽  
W. F. Novotny ◽  
...  
Keyword(s):  
Gene Expression ◽  
Radical Prostatectomy ◽  
Clinical Stage ◽  
Cleveland Clinic ◽  
Rt Pcr ◽  
Clinical Recurrence ◽  
T Stage ◽  
Gleason Pattern ◽  
Stage T1 ◽  
Baseline Psa

39 Background: Prostate biopsy may not adequately sample small, secondary or tertiary Gleason pattern tumors which can drive clinical outcome. We conducted a study to determine whether tumor-derived gene expression profiling could identify a distinct underlying biology associated with clinical recurrence (cR) after radical prostatectomy (RP) across both the primary and highest Gleason pattern (GP) samples. Methods: All patients (pts) with clinical stage T1/T2 prostate cancer treated with RP at Cleveland Clinic from 1987 to 2004 were identified (n∼f2,600). A cohort sampling design was used to select 127 patients with cR and 374 patients without cR after RP. Each patient had two spatially distinct tumor specimens sampled that included the primary GP and the highest GP. Surgical GS and clinical data were centrally reviewed. RNA was extracted from 6 manually dissected 10 μ m fixed paraffin embedded tissue sections obtained from the RP tumor specimens and expression of 732 cancer-related and reference genes was quantified using RT-PCR. Clinical recurrence-free interval (cRFI) was analyzed using Cox PH regression. Results: Blocks from 441 patients were evaluable. Median F/U was 5.8 years. Pts were mostly Caucasian (83%), clinical stage T1 (66%), had baseline PSA <10 ng/mL (82%), and had surgical GS ≤7 (87%). As expected, surgical GP, biopsy GP, path T- stage, clin T-stage, baseline PSA, and year of surgery (p<0.05, unadj) were associated with cRFI. In the primary and highest GP specimens respectively, 295 and 297 genes were significantly associated (unadj. p<0.05) with cRFI. 235 genes were associated with cRFI in both specimens, well in excess of the number expected by chance. In a multivariate model adjusted for AUA risk group and allowing a 10% false discovery rate, 289 genes remained significantly and strongly associated with cRFI. Conclusions: Gene expression analysis using quantitative RT-PCR identified a large number of genes, and underlying biology, that are strongly associated with clinical recurrence in both the primary and highest GP. This information can be used to develop a biopsy-based assay that distinguishes indolent versus aggressive disease. [Table: see text]

scholarly journals Gene expression signature of Gleason score is associated with prostate cancer outcomes in a radical prostatectomy cohort

Oncotarget ◽  
2017 ◽  
Vol 8 (26) ◽  
pp. 43035-43047 ◽  
Author(s):  
Min A. Jhun ◽  
Milan S. Geybels ◽  
Jonathan L. Wright ◽  
Suzanne Kolb ◽  
Craig April ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Gene Expression Signature ◽  
Cancer Outcomes ◽  
Expression Signature

Validation of a genomic-clinical classifier model for predicting clinical recurrence of patients with localized prostate cancer in a high-risk population.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 175-175 ◽  
Author(s):  
Robert B. Jenkins ◽  
Eric J Bergstralh ◽  
Elai Davicioni ◽  
R. Jeffrey Karnes ◽  
Karla V. Ballman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Risk Group ◽  
High Risk Group ◽  
High Risk Population ◽  
Clinical Recurrence ◽  
Clinical Variables ◽  
Subset Analysis

175 Background: The efficient delivery of adjuvant and salvage therapy after radical prostatectomy in patients with prostate cancer is hampered by a lack of biomarkers to assess the risk of clinically significant recurrence and progression. Methods: Mayo Clinic Radical Prostatectomy Registry (RP) patient specimens were selected from a case-control cohort with 14 years median follow-up for training and initial validation of an expression biomarker genomic classifier (GC). An independent, blinded case-cohort study of high-risk RP subjects was used to validate GC, comparing the performance of GC to a multivariate logistic regression clinical model (CM) and GC combined with clinical variables (genomic-clinical classifier, GCC) for predicting clinical recurrence (defined as positive bone or CT scan within 5 years after biochemical recurrence). The concordance index (c-index) and Cox model were used to evaluate discrimination and estimate the risk of clinical recurrence. Results: In the training subset (n=359), both GC and GCC had a c-index of 0.90 whereas CM had a c-index of 0.76. In the internal validation set (n=186), GC and GCC had a c-index of 0.76 and 0.75, while CM had a c-index of 0.69. In an independent high-risk study (n=219), GC and GCC had a c-index of 0.77 and 0.76, while CM had a c-index of 0.68. In subset analysis of Gleason score 7 patients within the high-risk group, GC and GCC showed improved discrimination with c-index of 0.78 and 0.76, respectively compared to 0.70 for CM. In the high-risk group, the risk of recurrence by GC model score quartiles at 5 years after RP was estimated at 1%, 5%, 5% and 18%. Conclusions: The GC model shows improved performance over CM in the prediction of clinical recurrence in a high-risk cohort and in subset analysis of Gleason score 7 patients. The addition of clinical variables to the GC model did not significantly contribute to classifier performance in patients with high-risk features. We are further testing the performance of the GC and GCC models and their usefulness in guiding decision-making (e.g., for the adjuvant therapy setting) in additional studies of prostate cancer clinical risk groups.

Evaluating the impact of African American ancestry among men with localized prostate cancer treated with radical prostatectomy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 41-41
Author(s):  
Daniel Canter ◽  
Julia E. Reid ◽  
Maria Latsis ◽  
Margaret Variano ◽  
Shams Halat ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Metastatic Disease ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Cox Proportional Hazards ◽  
Significant Difference ◽  
The Impact

41 Background: Prostate cancer (PC) is the most common male malignancy. Prior data has suggested that African American (AA) men present with more aggressive disease relative to men of other ancestries. Here, we examined the effects of ancestry on clinical and molecular measures of disease aggressiveness as well as pathologic outcomes in men treated with radical prostatectomy (RP) for localized PC. Methods: Data was collected from patients undergoing RP at the Ochsner Clinic from 2006 to 2011. Formalin−fixed paraffin embedded biopsy tissue was analyzed for the RNA expression of 31 cell cycle progression (CCP) genes and 15 housekeeping genes to obtain a CCP score (a validated molecular measure of PC aggressiveness). Cancer of the Prostate Risk Assessment (CAPRA) scores were also determined based on clinicopathologic features at the time of diagnosis. Clinical (Gleason score, tumor stage, CAPRA score) and molecular (CCP score) measures of disease aggressiveness were compared based on ancestry (AA versus non−AA). Cox proportional hazards models were used to test association of ancestry to biochemical recurrence (BCR) and progression to metastatic disease. Fisher’s exact and Wilcoxon rank sum tests were used to compare ancestries. Results: A total of 384 patients were treated with RP, including 133 (34.8%) AA men. At the time of diagnosis, the median age was 62 years (interquartile range (IQR) 56, 66) and PSA was 5.4 ng/mL (IQR 4.2, 7.6). When compared by ancestry, there were no significant differences in biopsy Gleason score (p = 0.26), clinical stage (p = 0.27), CAPRA score (p = 0.58), or CCP score (p = 0.87). In addition, there was no significant difference in the risk of BCR between ancestries (p = 0.55). Only non−AA men progressed to metastatic disease within the ten years of follow−up. Conclusions: Contrary to prior reports, these data appears to indicate that men of AA ancestry do not necessarily present with or develop a more biologically aggressive form of PC. Although these data represents only one institution’s experience, it contains a highly robust AA population compared to prior reports. Further research is required to account for the discrepancy in the previously published literature.

Use of a tissue biomarker panel to predict which men with a rising PSA post-definitive prostate cancer therapy will have systemic progression

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5017-5017
Author(s):  
R. B. Jenkins ◽  
T. Nakagawa ◽  
T. Kollmeyer ◽  
B. Morlan ◽  
E. Bergstrahl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Expression Pattern ◽  
Cancer Progression ◽  
Gene Expression Pattern ◽  
Prostate Cancer Progression ◽  
Definitive Therapy ◽  
Psa Recurrence ◽  
Additional Therapy

5017 Background: The majority of men with prostate cancer are diagnosed with cancers with low mortality. Such men are treated with radical prostatectomy, external beam radiotherapy, or brachytherapy and followed by serum PSA evaluations. Some men with a rising PSA therapy will have local recurrence or metastasis, but many will have no other evidence of recurrent disease other than a rising PSA. The PSA doubling time has been used to determine which of these men deserve adjuvant hormonal ablation, radiation therapy, or observation. We hypothesize that additional biomarkers will predict which men with a rising PSA post-definitive therapy would benefit from additional therapy. Methods: We designed a custom array containing 526 RNA targets whose expression has been reported to be altered in association with prostate cancer progression. We included targets from Mayo Clinic prostate cancer research. Together with a second commercial array, 530 genes implicated in prostate cancer progression and 420 other cancer-related genes were evaluated. A case-control design was used to test the association of the expression results with outcome. Cases were men post-radical prostatectomy who developed systemic progression within 5 years after PSA recurrence (N=213). Controls were matched men post-radical prostatectomy with PSA recurrence but no evidence of clinical progression within 5 years (N=213). Results: Of 426 eligible patients, paraffin blocks were available on 418 (98.1%). RNA was prepared from all 418 blocks, and both arrays were both successful on 405 (96.9%) RNAs. Upon univariate analysis, 40 genes were highly significantly over- or under-expressed in the cases versus controls (1x10-22 < p < 1x10-7). Recursive partitioning (RP) selected 4 genes (TPX2, FAM13C1, TOPO2A and TSP2) that distinguished cases from controls. Random Forest analysis selected 24 genes (including 3 of the RP 4). A multivariable ROC analysis using these 24 genes generated an AUC of 0.80 (95% CI: 0.75–0.84). Conclusions: A specific gene expression pattern was significantly associated with systemic progression after PSA recurrence. The measurement of gene expression pattern may be useful for determining which men may benefit from additional therapy after PSA recurrence. No significant financial relationships to disclose.

Subclassification of Clinical Stage T1 Prostate Cancer: Impact on Biochemical Recurrence Following Radical Prostatectomy

2007 ◽  
Vol 178 (4) ◽  
pp. 1277-1281 ◽  
Author(s):  
Ahmed Magheli ◽  
Soroush Rais-Bahrami ◽  
H. Ballentine Carter ◽  
Hugh J. Peck ◽  
Jonathan I. Epstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Biochemical Recurrence ◽  
Clinical Stage ◽  
Stage T1

scholarly journals Neuroendocrine Immunophenotype as Predictor of Clinical Recurrence in 110 Patients with Prostate Cancer

2007 ◽  
Vol 20 (4) ◽  
pp. 765-770 ◽  
Author(s):  
R. Autorino ◽  
M.G. Lamendola ◽  
G. De Luca ◽  
M. De Sio ◽  
F. Giugliano ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Median Time ◽  
Gleason Score ◽  
Biochemical Recurrence ◽  
Univariate Analysis ◽  
Localized Prostate Cancer ◽  
Clinical Recurrence ◽  
Psa Recurrence ◽  
Well Differentiated

We evaluated the relationship between NE expression and well-known prognostic factors and assessed whether tumor relapse after radical surgery correlates with the extent of NE differentiation. Radical prostatectomy specimens from 110 patients with clinically localized prostate cancer were assessed. Patients were followed up every three months for the first two years after surgery and six monthly for 5 additional years until failure, or for a mean of 48 months from the time of surgery for those who did not experience failure. The percentage of cells showing CgA immunoreactivity was evaluated using a visual quantitative method. Tumor staining was categorized as positive if >10% and negative if <10% of tumor cells were stained, to ensure that only cases with significant positivity were included in the positive group. The median follow-up was 5.4 years (range 1.8 to 7.2). The median time to clinical recurrence was 7.5 years and the median time to biochemical recurrence was 2.8 years. Of 31 patients (28%) who experienced a PSA recurrence, 15 developed a clinical recurrence. The mean preoperative PSA level was 9 ng/ml (range 2.7 to 25). Most cases were well differentiated (Gleason score <7), intraprostatic (≤pT2) tumors. Immunoreactivity in ≥10% of the cells was seen in 17.2% (n=19) of the tumor specimens. The preoperative PSA level, Gleason score, use of neoadjuvant or adjuvant therapy, lymphnode positivity were not statistically associated with NE expression. Only the primary pathologic stage appeared to be associated with CgA staining in the primary tumor (p=0.001). On the univariate analysis NE expression did not predict biochemical recurrence free survival, whereas it was associated with clinical recurrence. NE differentiation in clinically localized prostate cancer can be associated with failure after definitive surgical treatment, even if no conclusions can be drawn regarding its value as an independent prognostic factor.

Radical prostatectomy for clinically localized prostate cancer: long-term results of 1,143 patients from a single institution.

1994 ◽  
Vol 12 (11) ◽  
pp. 2254-2263 ◽  
Author(s):  
H Zincke ◽  
E J Bergstralh ◽  
M L Blute ◽  
R P Myers ◽  
D M Barrett ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
At Risk ◽  
Survival Rate ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Adjuvant Treatment ◽  
Clinical Stage ◽  
Survival Rates ◽  
Histologic Grade ◽  
Localized Prostate Cancer

PURPOSE To determine the efficacy and complication rate of radical prostatectomy (RP) as a treatment option for clinically localized prostate cancer (clinical stage < or = T2c). METHODS The study was a retrospective analysis of 1,143 consecutive patients (median age, 64 years; range, 38 to 79 y) who underwent RP at one institution (mean follow-up time, 9.7 years). Complications for this study population were compared with those of a contemporary group of 1,000 consecutive patients. RESULTS Of 1,143 patients, 83 (7%) had a low clinical stage (T1) and 160 (14%) had a low histologic grade (Gleason score < or = 3); 648 (57%) had a high clinical stage (T2b or T2c) and 204 (18%) had a high histologic grade (Gleason score > or = 7). Only 113 (10%) died of prostate cancer, and 177 (15%) developed metastasis. Adjuvant treatment (androgen deprivation or radiation therapy) was given in 197 (17%) patients (> or = pT3) and provided virtually identical results as without adjuvant treatment. The 10- and 15-year crude survival rates for 1,143 patients were 75% +/- 1.5% (SE) and 60% +/- 2.2%, respectively; the cause-specific survival rates were 90% +/- 1.1% and 83% +/- 1.9%, respectively; and the metastasis-free survival rates were 83% +/- 1.3% and 77% +/- 1.9%, respectively (398 men at risk at 10 years and 138 men at risk at 15 years). The 10-year survival rate for patients with Gleason score > or = 7 was 74% +/- 3.9%. Only tumor grade was a significant predictor for disease outcome. The hospital mortality rate decreased from 0.7% for the 1,143 study patients to 0% for the more recent 1,000 patients. Severe incontinence declined to 1.4% for the more recent 1,000 patients. Most patients who underwent RP were healthy (Charlson comorbidity index). CONCLUSION Survival at 15 years was similar to the expected survival rate. Current morbidity and mortality rates associated with RP were extremely low. Thus, RP has been a viable management option for men with clinically localized prostate cancer who have a life expectancy of more than 10 years.

scholarly journals Case: Spontaneous regression of post-radical prostatectomy prostate-specific antigen elevation without adjuvant therapy in a patient with lymph node metastasis

2017 ◽  
Vol 11 (7) ◽  
pp. E315-7
Author(s):  
Taehyoung Lee ◽  
Yanbo Guo ◽  
Saahil Vij ◽  
Rahul Bansal ◽  
Nathan C. Wong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Radical Prostatectomy ◽  
Adjuvant Therapy ◽  
Gleason Score ◽  
Clinical Stage ◽  
Specific Antigen ◽  
Surgical Margin ◽  
Lymph Node Involvement ◽  
Complete Regression

Prostate cancer remains the most frequently diagnosed cancer among men. The combination of clinical stage, serum prostatespecific antigen (PSA), and Gleason score (biopsy) assists in predictive assessment of pathological stage and prognosis. Furthermore, pathological criteria, including Gleason score, surgical margin status, extracapsular extension, seminal vesicle invasion, and lymph node involvement, provide prognostication in patients undergoing radical prostatectomy (RP). In this paper, we present a case of a patient with high-risk prostate cancer with persistent PSA elevation post-RP who experiences a complete regression of PSA without any adjuvant therapy. To the authors’ knowledge, such a finding has not been described in the literature previously.

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