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William L. Duren Jr., Andrew M. Gleason, and Peter J. Hilton Interview Transcripts
No full textDolph Briscoe Center for American Histor
Prognostic Utility of the Gleason Grading System Revisions and Histopathological Factors Beyond Gleason Grade
No full textBackground: The International Society of Urological Pathology (ISUP) revised the Gleason system in 2005 and 2014. The impact of these changes on prostate cancer (PCa) prognos-tication remains unclear. Objective: To evaluate if the ISUP 2014 Gleason score (GS) predicts PCa death better than the pre-2005 GS, and if additional histopathological information can further improve PCa death prediction. Patients and Methods: We conducted a case–control study nested among men in the National Prostate Cancer Register of Sweden diagnosed with non-metastatic PCa 1998–2015. We included 369 men who died from PCa (cases) and 369 men who did not (controls). Two uro-pathologists centrally re-reviewed biopsy ISUP 2014 Gleason grading, poorly formed glands, cribriform pattern, comedonecrosis, perineural invasion, intraductal, ductal and mucinous carcinoma, percentage Gleason 4, inflammation, high-grade prostatic intraepithelial neoplasia (HGPIN) and post-atrophic hyperplasia. Pre-2005 GS was back-transformed using i) information on cribriform pattern and/or poorly formed glands and ii) the diagnostic GS from the registry. Models were developed using Firth logistic regression and compared in terms of discrimination (AUC). Results: The ISUP 2014 GS (AUC = 0.808) performed better than the pre-2005 GS when back-transformed using only cribriform pattern (AUC = 0.785) or both cribriform and poorly formed glands (AUC = 0.792), but not when back-transformed using only poorly formed glands (AUC = 0.800). Similarly, the ISUP 2014 GS performed better than the diagnostic GS (AUC = 0.808 vs 0.781). Comedonecrosis (AUC = 0.811), HGPIN (AUC = 0.810) and number of cores with ≥50% cancer (AUC = 0.810) predicted PCa death independently of the ISUP 2014 GS. Conclusion: The Gleason Grading revisions have improved PCa death prediction, likely due to classifying cribriform patterns, rather than poorly formed glands, as Gleason 4. Comedonecrosis, HGPIN and number of cores with ≥50% cancer further improve PCa death discrimination slightly
Metabolomics of prostate cancer gleason score in tumor tissue and serum
No full textGleason score, a measure of prostate tumor differentiation, is the strongest predictor of lethal prostate cancer at the time of diagnosis. Metabolomic profiling of tumor and of patient serum could identify biomarkers of aggressive disease and lead to the development of a less-invasive assay to perform active surveillance monitoring. Metabolomic profiling of prostate tissue and serum samples was performed. Metabolite levels and metabolite sets were compared across Gleason scores. Machine learning algorithms were trained and tuned to predict transformation or differentiation status from metabolite data. A total of 135 metabolites were significantly different (Padjusted < 0.05) in tumor versus normal tissue, and pathway analysis identified one sugar metabolism pathway (Padjusted 1⁄4 0.03). Machine learning identified profiles that predicted tumor versus normal tissue (AUC of 0.82 ± 0.08). In tumor tissue, 25 metabolites were associated with Gleason score (unadjusted P < 0.05), 4 increased in high grade while the remainder were enriched in low grade. While pyroglutamine and 1,5-anhydroglu-citol were correlated (0.73 and 0.72, respectively) between tissue and serum from the same patient, no metabolites were consistently associated with Gleason score in serum. Previously reported as well as novel metabolites with differing abundance were identified across tumor tissue. However, a “metabolite signature” for Gleason score was not obtained. This may be due to study design and analytic challenges that future studies should consider
Narrative review of prostate cancer grading systems: Will the Gleason scores be replaced by the grade groups?
No full textThe Gleason grading system, proposed by Dr. Donald F. Gleason in 1966, is one of the most important prognostic factors in men with prostate cancer (PCa). At consensus conferences held in 2005 and 2014, organized by the International Society of Urological Pathology (ISUP), the system was modified to reflect the current diagnostic and therapeutic approaches. In particular, in the 2014 Conference, it was recognized that there were weaknesses with the original and the 2005 ISUP modified Gleason systems. Based on the results of a research conducted by Prof. JI Epstein and his group, a new grading system was proposed by the ISUP in order to address some of such deficiencies: i.e., the five distinct Grade Groups (GGs). Since 2014, results of studies have been published by different groups and societies, including the Genitourinary Pathology Society (GUPS), giving additional support to the prognostic role of the architectural Gleason patterns and, in particular, of the GGs. A revised GG system, taking into account the percentage of Gleason pattern (GP) 4, cribriform and intraductal carcinoma, tertiary GP 5, and reactive stroma grade, has shown to have some advantages, however not ready for adoption in the current practice. The aim of this contribution was to review the major updates and recommendations regarding the GPs and GSs, as well as the GGs, trying to give an answer to the following questions: “How has the grade group system been used in the routine?” and “will the Gleason scoring system be replace by the grade groups?” We also discussed the potential implementation in the future of molecular pathology and artificial intelligence in grading to further define risk groups in patients with PCa
Socio-economic inequalities in survival of patients with prostate cancer: role of age and Gleason grade at diagnosis
No full textIn the United Kingdom, survival of prostate cancer patients has improved since the 1990s. A deprivation gap in survival (better survival for the least deprived compared with the most deprived) has been reported but it is not known if differential distribution of earlier age or lower grade disease at diagnosis might explain such patterns. We therefore investigated the impact of age and Gleason grade at diagnosis on the deprivation gap in survival of prostate cancer patients over time. Incident cases of prostate cancer (ICD-10 C61) from the West of Scotland were extracted from the Scottish Cancer Registry from 1991 to 2007. Socio-economic circumstances were measured using the Scottish Index for Multiple Deprivation 2004 (SIMD). Age and deprivation specific mortality rates were obtained from the General Registrar Office for Scotland (GRO(S)). The survival gradient across the five deprivation categories was estimated with linear regression, weighted by the variance of the relative survival estimate. We examined the data for 15,292 adults diagnosed with prostate cancer between 1991 and 2007. Despite substantial improvements in survival of prostate cancer patients, a deprivation gap persists throughout the three periods of diagnoses. The deprivation gap in five year relative survival widened from −4.76 in 1991–1996 to −10.08 in 2003–2007. On age and grade-specific analyses, a significant deprivation gap in five year survival existed between all age groups except among patients' age ≥75 and both low and high grade disease. On multivariate analyses, deprivation was significantly associated with increased excess risk of death (RER 1.48, 95% CI 1.31–1.68, p-value<0.001) independent of age, Gleason grade and period of diagnosis. The deprivation gap in survival from prostate cancer cannot be wholly explained by socio-economic differentials in early detection of disease. Further research is needed to understand whether differences in comorbidities or treatment explain inequalities in prostate cancer outcomes
The reasons behind variation in Gleason grading of prostatic biopsies: areas of agreement and misconception among 266 European pathologists.
No full textAIMS: The Gleason scoring system underwent revision at the International Society of Urological Pathology (ISUP) conference in 2005. It is not known how uropathologists have interpreted its recommendations.
METHOD AND RESULTS: A web-based survey to European Network of Uropathology members received replies from 266 pathologists in 22 countries. Eighty-nine per cent claimed to follow ISUP recommendations. Key areas of disagreement included the following. Smoothly rounded cribriform glands were assigned Gleason pattern (GP) 3 by 51% and GP 4 by 49%. Necrosis was diagnosed as GP 5 by 62%. Any amount of secondary pattern of higher grade in needle biopsies was included in the Gleason score by 58%. Tertiary GP of higher grade on needle biopsies was included in the Gleason score by only 58%. If biopsy cores were embedded separately, only 56% would give a Gleason score for each core/slide examined; 68% would give a concluding Gleason score and the most common method was a global Gleason score (77%). Among those who blocked multiple biopsy cores together, 46% would only give an overall Gleason score for the case.
CONCLUSION: Misinterpretation of ISUP 2005 is widespread, and may explain the variation in Gleason scoring seen. Clarity and uniformity in teaching ISUP 2005 recommendations is necessary
Relação do antígeno prostático específico, escore do gleason e da percentagem de tumor na biópsia com estadiamento patológico no câncer de próstata.
No full textTrabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Dapartamento de Clínica Cirúrgica
Bayesian belief network for the Gleason patterns in prostatic adenocarcinoma: development of a diagnostic decision support system for educational purposes.
No full textOBJECTIVE: To develop a Bayesian belief network (BBN) for Gleason grading of prostate adenocarcinoma.
STUDY DESIGN: A shallow network was developed for Gleason grading with open-tree topology, with a root node containing 5 subjective diagnostic alternatives and 8 first-level descendant nodes for diagnostic features. Features or diagnostic clues of the descendant nodes were based on architecture of Gleason patterns. Data collected on 20 slides in the first and third slide circulations in the U.K.-based investigation of observer reproducibility of Gleason grading of prostatic biopsies were used. Circulations were called A and B. Level of agreement was studied using kappa statistics.
RESULTS: Mean of percentage agreements between subjective Gleason major pattern attributed to slides by pathologists and subjective Gleason major pattern most frequently assigned to each slide was 85% in A and 88% in B. Mean of percentage agreements between BBN reading for slides read by pathologists and BBN reading most frequently seen in each slide was 77% in A and 70% in B.
CONCLUSION: The BBN for Gleason grading is readily implemented, allowing use of linguistic variables and descriptive terms and accumulation of evidence presented by morphologic clues. This diagnostic decision support system has potential in pathology education
Interpolation and Gleason parts in 𝐿-domains
No full textWe describe the closure of
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, we describe all interpolation sequences for
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, we show that a homomorphism (except the distinguished homomorphism, when it exists) lies in a nontrivial Gleason part if and only if it is contained in the closure of an interpolating sequence, and we describe all the analytic structure occurring in
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A study of Gleason score interpretation in different groups of UK pathologists; techniques for improving reproducibility
No full textAims: To test the effectiveness of a teaching resource (a decision tree with diagnostic criteria based on published literature) in improving the proficiency of Gleason grading of prostatic cancer by general pathologists. Methods: A decision tree with diagnostic criteria was developed by a panel of urological pathologists during a reproducibility study. Twenty-four general histopathologists tested this teaching resource. Twenty slides were selected to include a range of Gleason score groups 2–4, 5–6, 7 and 8–10. Interobserver agreement was studied before and after a presentation of the decision tree and criteria. The results were compared with those of the panel of urological pathologists. Results: Before the teaching session, 83% of readings agreed within ± 1 of the panel's consensus scores. Interobserver agreement was low (κ = 0.33) compared with that for the panel (κ = 0.62). After the presentation, 90% of readings agreed within ± 1 of the panel's consensus scores and interobserver agreement amongst the pathologists increased to κ = 0.41. Most improvement in agreement was seen for the Gleason score group 5–6. Conclusions: The lower level of agreement among general pathologists highlights the need to improve observer reproducibility. Improvement associated with a single training session is likely to be limited. Additional strategies include external quality assurance and second opinion within cancer networks
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