The combination of DNA ploidy status and PTEN/6q15 deletions to provide strong and independent prognostic information in prostate cancer.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 5027-5027
Author(s):  
Maximilian Lennartz ◽  
Sarah Minner ◽  
Martina Kluth ◽  
Sophie Brasch ◽  
Hilko Wittmann ◽  
...  
2016 ◽  
Vol 22 (11) ◽  
pp. 2802-2811 ◽  
Author(s):  
Maximilian Lennartz ◽  
Sarah Minner ◽  
Sophie Brasch ◽  
Hilko Wittmann ◽  
Leonard Paterna ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4291
Author(s):  
Karolina Cyll ◽  
Andreas Kleppe ◽  
Joakim Kalsnes ◽  
Ljiljana Vlatkovic ◽  
Manohar Pradhan ◽  
...  

Machine learning (ML) is expected to improve biomarker assessment. Using convolution neural networks, we developed a fully-automated method for assessing PTEN protein status in immunohistochemically-stained slides using a radical prostatectomy (RP) cohort (n = 253). It was validated according to a predefined protocol in an independent RP cohort (n = 259), alone and by measuring its prognostic value in combination with DNA ploidy status determined by ML-based image cytometry. In the primary analysis, automatically assessed dichotomized PTEN status was associated with time to biochemical recurrence (TTBCR) (hazard ratio (HR) = 3.32, 95% CI 2.05 to 5.38). Patients with both non-diploid tumors and PTEN-low had an HR of 4.63 (95% CI 2.50 to 8.57), while patients with one of these characteristics had an HR of 1.94 (95% CI 1.15 to 3.30), compared to patients with diploid tumors and PTEN-high, in univariable analysis of TTBCR in the validation cohort. Automatic PTEN scoring was strongly predictive of the PTEN status assessed by human experts (area under the curve 0.987 (95% CI 0.968 to 0.994)). This suggests that PTEN status can be accurately assessed using ML, and that the combined marker of automatically assessed PTEN and DNA ploidy status may provide an objective supplement to the existing risk stratification factors in prostate cancer.


2015 ◽  
Vol 04 (02) ◽  
pp. 088-090 ◽  
Author(s):  
Anju Bansal ◽  
Anup Gupta ◽  
Sunita Saxena

Abstract Background: Prediction of biological behavior in patients of prostate cancer (CaP) is a major challenge as current parameters only partially meet the need for prognostication. p53 as a prognostic indicator has been studied in several human cancers, including breast, lung, and colorectal carcinoma. However, its significance as a predictive biomarker for CaP is less well-studied. Materials and Methods: This study included 125 cases of CaP, 27 cases of prostatic intraepithelial neoplasia and 25 cases of benign prostatic hyperplasia. Immunohistochemical assessment for p53 nuclear protein was performed. Assessment for apoptotic index and DNA ploidy status by flow cytometry were also done. Results: p53 immunoreactivity was low in organ confined CaP cases having Gleason score ≤3 (P < 0.003). More hormone resistant cases 37 (83%) were aneuploid when compared with hormone sensitive cases 26 (33%) (P < 0.005). 93% of p53 positive cases and none of the p53 negative patient were aneuploid suggesting a significant relation between p53 immunoreactivity and aneuploidy. p53 positivity and DNA aneuploidy, independently, were also predictors of progression and relapse. Conclusion: DNA ploidy and p53 positivity go hand in hand and together yield additional prognostic information in CaP. p53 positivity is possibly a late event in carcinogenesis in CaP and a marker of change in biological behavior of CaP.


1999 ◽  
Vol 23 (3) ◽  
pp. 296-301 ◽  
Author(s):  
Jeffrey S. Ross ◽  
Christine E. Sheehan ◽  
Robert A. Ambros ◽  
Tipu Nazeer ◽  
Timothy A. Jennings ◽  
...  

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e040965
Author(s):  
Sandra Miriam Kawa ◽  
Signe Benzon Larsen ◽  
John Thomas Helgstrand ◽  
Peter Iversen ◽  
Klaus Brasso ◽  
...  

ObjectiveTo investigate the risk of prostate cancer-specific mortality (PCSM) following initial negative systematic transrectal ultrasound-guided (TRUS) prostate biopsies.DesignSystematic review.Data sourcesPubMed and Embase were searched using a string combination with keywords/Medical Subject Headings terms and free text in the search builder. Date of search was 13 April 2020.Study selectionStudies addressing PCSM following initial negative TRUS biopsies. Randomised controlled trials and population-based studies including men with initial negative TRUS biopsies reported in English from 1990 until present were included.Data extractionData extraction was done using a predefined form by two authors independently and compared with confirm data; risk of bias was assessed using the Newcastle–Ottawa Scale for cohort studies when applicable.ResultsFour eligible studies were identified. Outcomes were reported differently in the studies as both cumulative incidence and Kaplan-Meier estimates have been used. Regardless of the study differences, all studies reported low estimated incidence of PCSM of 1.8%–5.2% in men with negative TRUS biopsies during the following 10–20 years. Main limitation in all studies was limited follow-up.ConclusionOnly a few studies have investigated the risk of PCSM following initial negative biopsies and all studies included patients before the era of MRI of the prostate. However, the studies point to the fact that the risk of PCSM is low following initial negative TRUS biopsies, and that the level of prostate-specific antigen before biopsies holds prognostic information. This may be considered when advising patients about the need for further diagnostic evaluation.PROSPERO registration numberCRD42019134548.


PROTEOMICS ◽  
2006 ◽  
Vol 6 (15) ◽  
pp. 4370-4380 ◽  
Author(s):  
Helena Lexander ◽  
Carina Palmberg ◽  
Ulf Hellman ◽  
Gert Auer ◽  
Magnus Hellström ◽  
...  

2013 ◽  
Author(s):  
Βασίλειος Τζελέπης

Objective: This study assesses the correlation of p53 immunoreactivity andp21 immunoreactivity with biochemical recurrence after radicalprostatectomy.Materials and Methods: P53 protein expression and p21 were evaluated on84 archival paraffin-embedded radical prostatectomy specimens. Patientswere divided into 2 groups for p533: patients with low (38/84, 45%) andpatients with high (46/84, 55%) p53 immunoreactivity and into 5 groups forp21. Patients with expression of p21<1%, patients with p21 expressionbetween 1 and 5%, patients with p21 expression between 5 and 10%,patients with p21 expression between 10 and 20% and finally patients withp21 expression over 20%. The results were correlated with Gleason score,DNA ploidy, stage and serum PSA. Kaplan-Meier biochemical recurrence freesurvival and Cox hazard-regression model were used for analysis.Results: Multivariate analysis revealed p53, DNA ploidy, Gleason score andstage to be independent prognostic factors in the order they are presented.Kaplan-Meier analysis showed a statistically significant difference inbiochemical recurrence when p53 high expression and DNA aneuploidy werecombined. P21 and PSA level according the previus analysis were notindependent prognostic factors. Conclusion: The results of this study suggest that stratification for p53expression, p21 expression and DNA ploidy status can provide additionalprognostic information for patients with prostate carcinoma after radicalprostatectomy.


2009 ◽  
Vol 27 (21) ◽  
pp. 3459-3464 ◽  
Author(s):  
Jennifer R. Stark ◽  
Sven Perner ◽  
Meir J. Stampfer ◽  
Jennifer A. Sinnott ◽  
Stephen Finn ◽  
...  

Purpose Gleason grading is an important predictor of prostate cancer (PCa) outcomes. Studies using surrogate PCa end points suggest outcomes for Gleason score (GS) 7 cancers vary according to the predominance of pattern 4. These studies have influenced clinical practice, but it is unclear if rates of PCa mortality differ for 3 + 4 and 4 + 3 tumors. Using PCa mortality as the primary end point, we compared outcomes in Gleason 3 + 4 and 4 + 3 cancers, and the predictive ability of GS from a standardized review versus original scoring. Patients and Methods Three study pathologists conducted a blinded standardized review of 693 prostatectomy and 119 biopsy specimens to assign primary and secondary Gleason patterns. Tumor specimens were from PCa patients diagnosed between 1984 and 2004 from the Physicians' Health Study and Health Professionals Follow-Up Study. Lethal PCa (n = 53) was defined as development of bony metastases or PCa death. Hazard ratios (HR) were estimated according to original GS and standardized GS. We compared the discrimination of standardized and original grading with C-statistics from models of 10-year survival. Results For prostatectomy specimens, 4 + 3 cancers were associated with a three-fold increase in lethal PCa compared with 3 + 4 cancers (95% CI, 1.1 to 8.6). The discrimination of models of standardized scores from prostatectomy (C-statistic, 0.86) and biopsy (C-statistic, 0.85) were improved compared to models of original scores (prostatectomy C-statistic, 0.82; biopsy C-statistic, 0.72). Conclusion Ignoring the predominance of Gleason pattern 4 in GS 7 cancers may conceal important prognostic information. A standardized review of GS can improve prediction of PCa survival.


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