SPOP and CHD1 alterations in prostate cancer: Relationship with PTEN loss, tumor grade, perineural infiltration, and PSA recurrence

The Prostate ◽  
2021 ◽  
Author(s):  
Silvia Hernández‐Llodrà ◽  
Laura Segalés ◽  
Nuria Juanpere ◽  
Tech Marta Lorenzo ◽  
Marta Salido ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Grade ◽  
Pten Loss ◽  
Psa Recurrence

1188: Time to PSA Recurrence after Radical Prostatectomy and Risk of Prostate Cancer Specific Mortality

2006 ◽  
Vol 175 (4S) ◽  
pp. 382-382
Author(s):  
Stephen J. Freedland ◽  
Elizabeth B. Humphreys ◽  
Leslie A. Mangold ◽  
Mario Eisenberger ◽  
Alan W. Partin
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Specific Mortality ◽  
Psa Recurrence ◽  
Cancer Specific Mortality

scholarly journals Transcriptional landscape of PTEN loss in primary prostate cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eddie Luidy Imada ◽  
Diego Fernando Sanchez ◽  
Wikum Dinalankara ◽  
Thiago Vidotto ◽  
Ericka M. Ebot ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Meta Analysis ◽  
Pten Loss ◽  
Primary Prostate Cancer ◽  
Expression Atlas ◽  
Transcriptomic Signature ◽  
Transcriptional Changes ◽  
New Biomarkers ◽  
Adaptive Immune Systems ◽  
Transcriptional Landscape

Abstract Background PTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. In this study, we highlight the transcriptional changes associated with PTEN loss in PCa. Methods Using a meta-analysis approach, we leveraged two large PCa cohorts with experimentally validated PTEN and ERG status by Immunohistochemistry (IHC), to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. This signature was expanded to lncRNAs using the TCGA quantifications from the FC-R2 expression atlas. Results The signatures indicate a strong activation of both innate and adaptive immune systems upon PTEN loss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. Highlighting potential novel lncRNAs associated with PTEN loss and PCa progression. Conclusion We created a PCa specific signature of the transcriptional landscape of PTEN loss that comprises both the coding and an extensive non-coding counterpart, highlighting potential new players in PCa progression. We also show that contrary to what is observed in other cancers, PTEN loss in PCa leads to increased activation of the immune system. These findings can help the development of new biomarkers and help guide therapy choices.

Prostate Cancer: Population-Based Survival Rates in Central Italy

1995 ◽  
Vol 81 (2) ◽  
pp. 81-85 ◽  
Author(s):  
Emanuele Crocetti ◽  
Eva Buiatti ◽  
Andrea Amorosi
Keyword(s):  
Prostate Cancer ◽  
Central Italy ◽  
Survival Rates ◽  
Relative Survival ◽  
Tumor Grade ◽  
Population Based ◽  
Prognostic Effect ◽  
Disease Extension ◽  
The One ◽  
Histological Verification

Aims To evaluate survival in prostate cancer patients in the Province of Florence where the Tuscany Cancer Registry is active. Methods The survival of 777 patients with prostate cancer diagnosed in the period 1985-87 was evaluated. The observed and relative survival rates 1, 3 and 5 years after diagnosis were computed. Also the prognostic effect of age, disease extension, tumor grade, histological verification, place of residence and year of diagnosis were evaluated using univariate and multivariate analysis. Results The observed survival was 73.4% 1 year, 42.5% 3 years and 29.2% 5 years after diagnosis. The relative survival was respectively 78.7%, 53.0% and 43.0%. Significant independent risks were evident when the disease was extended out of the prostate, for patients older than 80 years, for high grade tumors and for patients without histological verification. Conclusion The 5-year relative survival rate in the province of Florence is similar to those from other European Registries and the Latina Registry, but much lower than the one reported by the SEER program in the US. Data on histological verification percentage, availability of information on disease extension, and tumor grade are discussed as indicators of the quality of the diagnostic approach in comparison with other registries.

scholarly journals Early detection of prostate cancer local recurrence by urinary prostate-specific antigen

2013 ◽  
Vol 3 (3) ◽  
pp. 213 ◽  
Author(s):  
Stéphane Bolduc ◽  
Brant A. Inman ◽  
Louis Lacombe ◽  
Yves Fradet ◽  
Roland R. Tremblay
Keyword(s):  
Prostate Cancer ◽  
Early Detection ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Laboratory Assessment ◽  
Cross Sectional ◽  
Prostatectomie Radicale ◽  
Psa Recurrence ◽  
Patients Atteints De Cancer

Purpose: We assessed the role of urinary prostate-specific antigen(uPSA) in the follow-up of prostate cancer after retropubic radicalprostatectomy (RRP) for the early detection of local recurrences.Methods: We recruited 50 patients previously treated for prostatecancer with RRP and who had not experienced a prostatespecificantigen (PSA) recurrence within their first postoperativeyear into a cross-sectional laboratory assessment and prospective6-year longitudinal follow-up study. We defined biochemicalfailure as a serum PSA (sPSA) of 0.3 μg/L or greater. Patientsprovided blood samples and a 50-mL sample of first-voided urine.We performed Wilcoxon rank-sum and Fisher exact tests for statisticalanalysis.Results: The median sPSA was 0.13 μg/L. The median uPSA was0.8 μg/L, and was not significantly different when comparingGleason scores or pathological stages. Of the 50 patients, 27 initiallyhad a nondetectable sPSA but a detectable uPSA, and11 patients experienced sPSA failure after 6 years. Six patients haddetectable sPSA and uPSA initially. Fifteen patients were negativefor both sPSA and uPSA, and 13 remained sPSA-free after 6 years.The odds ratio (OR) of having sPSA failure given a positive uPSAtest was 4.5 if sPSA was undetectable, but was reduced to 2.6 ifsPSA was detectable. The pooled Mantel–Haenszel OR of 4.2 suggestedthat a detectable uPSA quadrupled the risk of recurrence,independent of whether sPSA was elevated or not. The sensitivityof uPSA for detecting future sPSA recurrences was 81% andspecificity was 45%.Conclusion: Urinary PSA could contribute to an early detection oflocal recurrences of prostate cancer after a radical prostatectomy.Objectif : Nous avons évalué le rôle de l’antigène prostatiquespécifique (APS) urinaire dans le suivi du cancer de la prostateaprès prostatectomie radicale rétropubienne (PRR) pour le dépistageprécoce de récidives locales.Méthodes : Cinquante patients atteints de cancer de la prostatetraités par PRR et n’ayant présenté aucune récidive avec anomaliede l’APS dans l’année suivant l’intervention chirurgicale ontété inscrits à une étude transversale par épreuves de laboratoireavec suivi longitudinal prospectif sur 6 ans. L’échec sur le planbiochimique était défini comme un taux d’APS sérique de 0,3 μg/Lou plus. Les patients devaient fournir des échantillons de sanget un échantillon d’urine du matin de 50 mL. Les analyses statistiquesreposaient sur le test de Wilcoxon et la méthode exactede Fisher.Résultats : La valeur médiane de l’APS sérique était de 0,13 μg/L.La valeur médiane de l’APS urinaire était de 0,8 μg/L; la différenceétait non significative quand on tenait compte des scores deGleason ou des stades pathologiques. Sur les 50 patients,27 présentaient des taux d’APS sérique non décelables au début,mais des taux d’APS urinaire décelables; 11 patients ont présentéun échec quant aux taux d’APS sérique après 6 ans. Six patientsavaient des taux d’APS sérique et urinaire décelables au départ.Quinze patients n’avaient aucun taux décelable d’APS sérique ouurinaire, et aucun APS sérique n’était toujours décelable chez13 patients après 6 ans. Le rapport de risque d’un échec quantaux taux d’APS sérique après détection d’APS urinaire est de 4,5en l’absence d’un taux d’APS sérique décelable, mais diminueà 2,6 en présence d’un taux d’APS sérique décelable. Le rapportde risque cumulé de 4,21 calculé par la méthode deMantel–Haenszel porte à croire que des taux d’APS urinaire décelablesquadruplent le risque de présenter une récidive, queles taux sériques soient élevés ou non. La sensibilité du test dedépistage de l’APS urinaire pour la détection des récidives avecanomalie des taux sériques était de 81 %, et la spécificité, de 45 %.Conclusion : Le taux d’APS urinaire peut contribuer à un dépistageprécoce des récidives locales après une prostatectomie radicale.

scholarly journals Molecular Characterization of Prostate Cancer in Middle Eastern Population Highlights Differences with Western Populations with Prognostic Implication

2019 ◽  
Author(s):  
Ramy A. Abdelsalam ◽  
Ibrahim Khalifeh ◽  
Alan Box ◽  
Maria Kalantarian ◽  
Sunita Ghosh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Middle Eastern ◽  
Genomic Alteration ◽  
Published Data ◽  
Lower Grade ◽  
Eastern Population ◽  
Western Population ◽  
Pten Loss ◽  
Middle Eastern Population ◽  
Grade Groups

Abstract Background To investigate the incidence and prognostication of ERG, PTEN and SPINK1 protein expressions in prostate cancer cohort of Middle Eastern descent in comparison to published data from Western populationMethods Immunohistochemistry for ERG, PTEN and SPINK1 was performed in cohort of localized PCa (n=340). Data correlated to pathological and clinical outcomes and compared to Western populations.Results ERG expression and PTEN loss noted in 123/288 (42.7%) and 91/297 (30.6%) of patients, respectively. SPINK1 expression assessed in subset of cases, noted in 6/150 (4%) of patients. Only ERG expression was associated with grade groups, being more common in lower grade groups (1-3 vs 4-5; p=0.04). In contrast to Western population, PTEN loss foci were more likely to be ERG negative, observed in 81% of tumor foci and patients with PTEN neg/ERG pos were more likely to exhibit biochemical recurrence (OR 2.831; 95% CI: 1.10-726, p=0.03). This association remained significant in multivariate analysis (OR 2.68; 95% CI: 0.98-7.33, p=0.05), after adjusting for GG, path stage and surgical margin.Conclusion This study documents significant differences in key molecular events in PCa in Middle Eastern population compared to Western populations that could explain differences in PCa incidence, progression and prognostication. ERG, PTEN and SPINK1 genomic alteration occur less frequently and the enrichment of ERG for PTEN loss is not observed. Additionally, patients with combined PTEN loss/ERG positive are at highest rate for BCR vs North American Caucasian population where PTEN loss alone seems to be associated with the worst clinical outcome. The data presented here further support differences in clonal evolution between Middle Eastern and Western population in relation to PCa and add further insight to understanding PCa molecular pathways.

scholarly journals Overview of the Development and Use of Akt Inhibitors in Prostate Cancer

2021 ◽  
Vol 11 (1) ◽  
pp. 160
Author(s):  
Anis Gasmi ◽  
Guilhem Roubaud ◽  
Charles Dariane ◽  
Eric Barret ◽  
Jean-Baptiste Beauval ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Phase Ii ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Loss Of Function ◽  
Pten Loss ◽  
Castration Resistant ◽  
Recent Phase ◽  
Phase Ii And Iii

Deregulation of the PI3K-Akt-mTOR pathway plays a critical role in the development and progression of many cancers. In prostate cancer, evidence suggests that it is mainly driven by PTEN loss of function. For many years, the development of selective Akt inhibitors has been challenging. In recent phase II and III clinical trials, Ipatasertib and Capivasertib associated with androgen deprivation therapies showed promising outcomes in patients with metastatic castration-resistant prostate cancer and PTEN-loss. Ongoing trials are currently assessing several Akt inhibitors in prostate cancer with different combinations, at different stages of the disease.

MP79-08 PTEN LOSS IN LOCALIZED PROSTATE CANCER: CLINICOPATHOLOGIC PARAMETERS AND RELATIONSHIP WITH DISEASE OUTCOME

2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
Lisly Chery ◽  
Johnathan L. Wright ◽  
Daniel W. Lin ◽  
Xiaoyu Qu ◽  
Min Fang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Localized Prostate Cancer ◽  
Disease Outcome ◽  
Pten Loss ◽  
Clinicopathologic Parameters

scholarly journals Relationship between tumor grade and geometrical complexity in prostate cancer

2015 ◽  
Author(s):  
José Llanos Pérez ◽  
Eduardo Tejera Puente ◽  
Elena Izquierdo Kulich ◽  
Juvencio A Betancourt MAr ◽  
Manuel Nistal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Grade ◽  
Prognostic Indicator ◽  
Histological Evaluation ◽  
Gleason Grade ◽  
Therapy Planning ◽  
Tissue Architecture ◽  
Visual Grading ◽  
Geometrical Complexity ◽  
Architectural Patterns

Prostate cancer exhibits high mathematical complexity due to the disruption of tissue architecture. An important part of the diagnostic of prostate tumor samples is the histological evaluation of cellular and glandular organization. The Gleason grade and score, a commonly used prognostic indicator of patient outcome, is based on the match of glandular architectural patterns with standard patterns. Unfortunately, the subjective nature of visual grading leads to variations in scoring by different pathologists. We proposed the fractal dimension of the lumen and the Lempel-Zip complexity of the histopathological patterns as useful descriptors aiding pathologist to standardize histological classification and thus prognosis and therapy planning.

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