Association of expression of ERG oncoprotein with development of disease recurrence and prostate cancer-specific mortality.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15207-e15207
Author(s):  
Richard Johnston ◽  
Elysia Sophia Spencer ◽  
Xiaoyu Qu ◽  
Cigdem Himmetoglu Ussakli ◽  
Ryan Robert Gordon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Recurrent Disease ◽  
Medical Center ◽  
Disease Recurrence ◽  
Patient Treatment ◽  
Genomic Alteration ◽  
Expression Intensity ◽  
Specific Mortality ◽  
Cancer Specific Mortality

e15207 Background: ETS-Related Gene (ERG) protein is present in approximately half of prostate cancer (PCa) specimens and correlates with TMPRSS2-ERG rearrangement. ERG oncogenic activation is believed to be a causal genomic alteration in a significant portion of PCa, its prognostic value in disease progression remains uncertain. This study evaluated ERG levels at radical prostatectomy (RP) to determine if it was predictive of earlier relapse or prostate cancer-specific mortality (PCSM). Methods: From 1954-1997, 1004 consecutive patients underwent RP at Virginia Mason Medical Center in Seattle. Recurrence was confirmed by tissue diagnosis or radiographic signs. Death certificates confirmed PCSM. Patients without tissue were excluded. 34 patients with metastases or PCSM were matched to patients without recurrence at a 1:2 ratio. Paraffin embedded tissue was stained with two anti-ERG monoclonal antibodies, clone 9FY (Furustao et al., PCPD, 2010) and clone EPR3864 (Epitomics, Burlingame, CA). A pathologist evaluated the nuclear expression intensity using a 4-point scale. Statistical analysis was performed on SAS. Results: Mean follow up was 10.26 yrs.Antibody 9FY detected ERG in 10/16 (62.5%) PCSM and 24/44 (54.6%) no recurrence patients. Cancer expression intensity was higher from patients that developed recurrent disease, 0.99 vs 1.59 (p = 0.0265) and PCSM 2.09 (p = 0.0002). Antibody EPR3864 detected ERG in 11/17 (64.7%) PCSM and 26/48 (52.1%) no recurrence patients. Cancer expression intensity was higher from patients that developed recurrent disease, 0.97 vs 1.64 (p = 0.011) and PCSM, 2.30 (p < 0.0001). The two antibodies were independent of PSA and grade and were highly correlated with each other (p < 0.0001). Conclusions: ERG expression at time of surgery was prognostic for the development of disease recurrence and PCSM. Previous studies have shown an increased lifetime risk of PCSM with ERG expression in a surveillance cohort. This is the first report linking PCSM to ERG expression in men treated with surgery. ERG scoring may be a useful metric to identify patients who would benefit from adjuvant treatment or closer follow-up, allowing more accurate individual patient treatment plans.

Association of decreased expression of protein phosphatase 2A subunit PR55γ (PPP2R2C) with an increased risk of metastases and prostate cancer-specific mortality.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4669-4669
Author(s):  
Elysia Sophia Spencer ◽  
Eric Gregory Bluemn ◽  
Richard Johnston ◽  
Xiaotun Zhang ◽  
Ryan Robert Gordon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Phosphatase ◽  
Medical Center ◽  
Protein Phosphatase 2A ◽  
Patient Treatment ◽  
Gleason Grade ◽  
Increased Risk ◽  
Specific Mortality ◽  
Phosphatase 2A ◽  
Cancer Specific Mortality

4669 Background: The protein phosphatase 2A (PP2A) holoenzyme complex negatively controls cell growth, differentiation and apoptosis. Down regulation of PP2A activity is associated with oncogenic transformation of papillomas and is a target for the small-T viral oncogene. The PR55γ (2R2C) subunit regulates PP2A target specificity, inhibiting c-Src activity in some cell lines. c-Src activity enhances growth and invasion in prostate cancer. This study evaluates whether PPP2R2C protein levels in radical prostatectomy (RP) specimens were predictive for the development of metastases or prostate-cancer specific mortality (PCSM). Methods: From 1954-1997, 1004 consecutive patients underwent RP at Virginia Mason Medical Center in Seattle. Metastases were confirmed radiographically or by tissue diagnosis. Death certificates confirmed PCSM. Patients without stored tissue were excluded. 34 patients with metastases or PCSM were matched to patients without recurrence (NR) at a 1:2 ratio. Paraffin-embedded tissue was stained with anti-PPP2R2C monoclonal antibody, clone 6D1 (Abnova, Taiwan). A pathologist evaluated the percentage and intensity of nuclei stained using a 4-point scale. Statistical analysis was performed on SAS. Results: Mean follow up was 10.26 years. PPP2R2C was detected in 13/18 (72.2%) PCSM, 18/22 (81.8%) metastases and 45/49 (91.8%) NR patients. Mean expression was lower in cancerous vs benign glands, 1.74 vs 2.04 (p = 0.001). Expression intensity from PCSM vs NR was 1.45 vs 1.80 (p = 0.041). On multivariate analysis, expression was lower in metastases or PCSM versus NR 1.79 vs 2.35 (p = 0.002), independent of pre-op PSA and Gleason grade. Conclusions: PPP2R2C loss was highly correlated with metastasis and PCSM. Patients with the lowest levels of expression were at the highest risk for PCSM. As tissue was obtained at time of surgery, this analysis reflects a truly prognostic biomarker, independent of Gleason grade and PSA. We have shown that PPP2R2C scoring is a useful metric to identify patients at high risk of developing advanced disease. With further validation may allow for more accurate individual patient treatment plans and counseling.

The association of very low PSA with increased cancer-specific death in men with high-grade prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 62-62
Author(s):  
Brandon Arvin Virgil Mahal ◽  
Ayal Aaron Aizer ◽  
Jason Alexander Efstathiou ◽  
Paul Linh Nguyen
Keyword(s):  
Prostate Cancer ◽  
Reference Group ◽  
High Grade ◽  
Specific Mortality ◽  
National Cohort ◽  
Poorly Differentiated ◽  
Cancer Specific Mortality ◽  
Prostate Cancers ◽  
Very High

62 Background: It has been hypothesized that very low PSAs in men with high-grade prostate cancer could reflect dedifferentiation and a poorer prognosis, but clinical evidence to support this is limited. We sought to determine whether a very low-presenting PSA was associated with greater prostate cancer-specific mortality (PCSM) among men with Gleason score (GS) 8-10 disease. Methods: The Surveillance, Epidemiology and End Results Program was used to identify a national cohort of 328,904 men diagnosed with cT1-4N0M0 prostate cancer between 2004 and 2010. Multivariable Fine-Gray competing-risks regression analysis was used to determine PCSM as a function of PSA level (<2.5 ng/mL, 2.6-4 ng/mL, 4.1-10 ng/mL, 10.1-20 ng/mL, 20.1-40 ng/mL, or >40ng/mL) and GS (8-10 vs. <=7). Results: Median follow-up was 38 months. Among men with GS 8-10 disease, using PSA 4.1-10 as the reference group, the Adjusted HR (AHR) for PCSM for men with PSA level <2.5 was 1.86 (95% CI 1.51-2.29; P<0.001), PSA 2.6-4 was1.44 (1.17-1.78; P<0.001), PSA 10.1-20 was 1.58 (1.39-1.78; P<0.001), PSA 20.1-40 was 2.04 (1.78-2.33; P<0.001), and PSA>40 was 3.19 (2.83-3.59; P<0.001), suggesting a U-shaped distribution. There was a significant interaction between PSA level and GS (Pinteraction<0.001) such that PSA <2.5 only significantly predicted for poorer PCSM among patients with high grade GS 8-10 disease. Conclusions: Among patients with high grade GS 8-10 disease, patients with PSA <2.5 and 2.6-4 appear to have a higher risk for cancer-specific death compared to patients with a 10.1-20 PSA level, supporting the notion that low PSA in GS 8-10 disease may be a sign of underlying aggressive and extremely poorly differentiated or anaplastic low PSA-producing tumors. Patients with low PSA GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents in very-high risk prostate cancers.

PREDICTORS OF PROSTATE CANCER SPECIFIC MORTALITY AMONG MEN WITH RECURRENT DISEASE AFTER RADICAL PROSTATECTOMY

2009 ◽  
Vol 181 (4S) ◽  
pp. 271-272
Author(s):  
Thomas Chi ◽  
Matthew R. Cooperberg ◽  
Alan T Paciorek ◽  
Peter R. Carroll
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Recurrent Disease ◽  
Specific Mortality ◽  
Cancer Specific Mortality

scholarly journals Predicting prostate cancer specific-mortality with artificial intelligence-based Gleason grading

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Ellery Wulczyn ◽  
Kunal Nagpal ◽  
Matthew Symonds ◽  
Melissa Moran ◽  
Markus Plass ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Artificial Intelligence ◽  
Risk Groups ◽  
Risk Scores ◽  
Pathology Report ◽  
Gleason Grading ◽  
Specific Mortality ◽  
Cancer Specific Mortality ◽  
Open Question

Abstract Background Gleason grading of prostate cancer is an important prognostic factor, but suffers from poor reproducibility, particularly among non-subspecialist pathologists. Although artificial intelligence (A.I.) tools have demonstrated Gleason grading on-par with expert pathologists, it remains an open question whether and to what extent A.I. grading translates to better prognostication. Methods In this study, we developed a system to predict prostate cancer-specific mortality via A.I.-based Gleason grading and subsequently evaluated its ability to risk-stratify patients on an independent retrospective cohort of 2807 prostatectomy cases from a single European center with 5–25 years of follow-up (median: 13, interquartile range 9–17). Results Here, we show that the A.I.’s risk scores produced a C-index of 0.84 (95% CI 0.80–0.87) for prostate cancer-specific mortality. Upon discretizing these risk scores into risk groups analogous to pathologist Grade Groups (GG), the A.I. has a C-index of 0.82 (95% CI 0.78–0.85). On the subset of cases with a GG provided in the original pathology report (n = 1517), the A.I.’s C-indices are 0.87 and 0.85 for continuous and discrete grading, respectively, compared to 0.79 (95% CI 0.71–0.86) for GG obtained from the reports. These represent improvements of 0.08 (95% CI 0.01–0.15) and 0.07 (95% CI 0.00–0.14), respectively. Conclusions Our results suggest that A.I.-based Gleason grading can lead to effective risk stratification, and warrants further evaluation for improving disease management.

Daily Aspirin Use and Prostate Cancer–Specific Mortality in a Large Cohort of Men with Nonmetastatic Prostate Cancer

2014 ◽  
Vol 32 (33) ◽  
pp. 3716-3722 ◽  
Author(s):  
Eric J. Jacobs ◽  
Christina C. Newton ◽  
Victoria L. Stevens ◽  
Peter T. Campbell ◽  
Stephen J. Freedland ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Recent Analysis ◽  
Clinical Database ◽  
Specific Mortality ◽  
Cancer Specific Mortality ◽  
Daily Aspirin ◽  
High Doses ◽  
Large Prospective Cohort

Purpose In a recent analysis of a large clinical database, postdiagnosis aspirin use was associated with 57% lower prostate cancer–specific mortality (PCSM) among men diagnosed with nonmetastatic prostate cancer. However, information on this association remains limited. We assessed the association between daily aspirin use and PCSM in a large prospective cohort. Patients and Methods This analysis included men diagnosed with nonmetastatic prostate cancer between enrollment in the Cancer Prevention Study-II Nutrition Cohort in 1992 or 1993 and June 2009. Aspirin use was reported at enrollment, in 1997, and every 2 years thereafter. During follow-up through 2010, there were 441 prostate cancer deaths among 8,427 prostate cancer cases with information on prediagnosis aspirin use and 301 prostate cancer deaths among 7,118 prostate cancer cases with information on postdiagnosis aspirin use. Results Compared with no aspirin use, neither prediagnosis nor postdiagnosis daily aspirin use were statistically significantly associated with PCSM (prediagnosis use, multivariable-adjusted hazard ratio (HR) = 0.92, 95% CI 0.72 to 1.17, postdiagnosis use, HR = 0.98; 95% CI, 0.74 to 1.29). However, among men diagnosed with high-risk cancers (≥ T3 and/or Gleason score ≥ 8), postdiagnosis daily aspirin use was associated with lower PCSM (HR = 0.60; 95% CI, 0.37 to 0.97), with no clear difference by dose (low-dose, typically 81 mg per day, HR = 0.50; 95% CI, 0.27 to 0.92, higher dose, HR = 0.73; 95% CI, 0.40 to 1.34). Conclusion A randomized trial of aspirin among men diagnosed with nonmetastatic prostate cancer was recently funded. Our results suggest any additional randomized trials addressing this question should prioritize enrolling men with high-risk cancers and need not use high doses.

The Association between pre-operative PSA and prostate cancer-specific mortality in patients with long-term follow-up after radical prostatectomy

The Prostate ◽  
2011 ◽  
Vol 72 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Dan Lewinshtein ◽  
Brandon Teng ◽  
Ashley Valencia ◽  
Robert Gibbons ◽  
Christopher R. Porter
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Specific Mortality ◽  
Long Term Follow Up ◽  
Cancer Specific Mortality

scholarly journals Prospective Study of Prostate Tumor Angiogenesis and Cancer-Specific Mortality in the Health Professionals Follow-Up Study

2009 ◽  
Vol 27 (33) ◽  
pp. 5627-5633 ◽  
Author(s):  
Lorelei A. Mucci ◽  
Anna Powolny ◽  
Edward Giovannucci ◽  
Zhiming Liao ◽  
Stacey A. Kenfield ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Microvessel Density ◽  
Health Professionals ◽  
Prostate Cancer Mortality ◽  
Follow Up Study ◽  
Vessel Lumen ◽  
Specific Mortality ◽  
Cancer Specific Mortality ◽  
And Function

Purpose Tumor growth requires the development of independent vascular networks that are often primitive in morphology and function. We examined whether microvessel morphology contributes to the considerable biologic heterogeneity of prostate cancer. Methods We evaluated microvessel morphology as a predictor of prostate cancer mortality among 572 men in the Health Professionals Follow-Up Study diagnosed with cancer during 1986 to 2000. We immunostained prostatectomy tumor block sections for endothelial marker CD34 and assessed microvessel density, vessel size (area and diameter), and irregularity of vessel lumen using image analysis. Proportional hazards models were used to assess microvessel density and morphology in relation to lethal prostate cancer. Results Poorly differentiated tumors exhibited greater microvessel density, greater irregularity of the vessel lumen, and smaller vessels. During 20 years of follow-up, 44 men developed bone metastases or died of cancer. Men with tumors exhibiting the smallest vessel diameter, based on quartiles, were 6.0 times more likely (95% CI, 1.8 to 20.0) to develop lethal prostate cancer. Men with the most irregularly shaped vessels were 17.1 times more likely (95% CI, 2.3 to 128) to develop lethal disease. Adjusting for Gleason grade and prostate-specific antigen levels did not qualitatively change the results. Microvessel density was not linked to cancer-specific mortality after adjusting for clinical factors. Conclusion Aggressive tumors form vessels that are primitive in morphology and function, with consequences for metastases. Vascular size and irregularity reflect the angiogenic potential of prostate cancer and may serve as biomarkers to predict prostate cancer mortality several years after diagnosis.

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