Spatial Genomics Identifies Heat Shock Proteins as Key Molecular Changes Associated to Adipose Periprostatic Space Invasion in Prostate Cancer.

Purpose: To identify molecular changes during PCa invasion of adipose space using Spatial Transcriptomic Profiling of PCa cells.

Methods: This study was performed on paired intraprostatic and extraprostatic samples obtained from radical prostatectomy with pT3a pathological stages.

Results: Differential gene expression revealed upregulation of heat shock protein genes: DNAJB1, HSPA8, HSP90AA1, HSPA1B, HSPA1A in PCa PanCK+ cells from the adipose periprostatic space.

A collaborative review of the microsatellite instability/deficient mismatch repair phenotype in patients with upper tract urothelial carcinoma.

Objective: To perform a collaborative review of the literature exploring the microsatellite instability/deficient mismatch repair (MSI/dMMR) phenotype in patients with upper tract urothelial carcinoma (UTUC).

Method: A collaborative review of the literature available on Medline was conducted by the Cancer Committee of the French Association of Urology to report studies describing the genetic mechanisms, investigation, prevalence and impact of the MSI/dMMR phenotype in UTUC patients.

Results: The predominant genetic mechanism leading to the MSI/dMMR phenotype in UTUC patients is related to the constitutional mutation of one allele of the MMR genes MLH1, MSH2, MSH6 and PMS2 within Lynch syndrome.

A Comprehensive National Survey of Prostate-specific Antigen Testing and Prostate Cancer Management in France: Uncovering Regional and Temporal Disparities.

We report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men. All prostate-specific antigen (PSA) blood tests performed between 2006 and 2018 were recorded in a National Health registry, which allowed to identify 692516 men diagnosed with PC and a control population consisting of 3899509 men without PC. PSA tests, age at diagnosis, treatments, and survival were analysed.

Tumour-based Mutational Profiles Predict Visceral Metastasis Outcome and Early Death in Prostate Cancer Patients.

Background: Visceral metastases are known to occur in advanced prostate cancer, usually when the tumour is resistant to androgen deprivation and, have worse outcomes regardless of therapies.

Objective: To analyse genomic alterations in tumour samples according to their lymphatic, bone, and visceral metastatic stages and overall survival.

Design, Setting, And Participants: We selected 200 patients with metastatic prostate cancer.

Use of genomic markers to improve epidemiologic and clinical research in urology.

Purpose Of Review: Urologic cancers result from the appearance of genomic alterations in the target organ due to the combination of genetic and environmental factors. Knowledge of the genomic markers involved in their etiology and mechanisms for their development continue to progress. This reviewed provides an update on recent genomic studies that have informed epidemiologic and clinical research in urology.

Endemic statistical paradoxes in epidemiologic studies distort knowledge on prostate cancer: mitigation and caution of fallacies in prostate cancer causal epidemiological studies.

Purpose Of Review: Many studies on epidemiology of prostate cancer (PCa) are based on a diagnosis of PCa using PSA (prostate-specific antigen) level. However, biases can distort the interpretation of the results, which in turn limits policy and decision making on public health prevention strategies or clinical guidelines. The main confusion is to interpret the posterior probability of the outcome following the exposure as a change in the prevalence of the disease outcome, whereas this change reflects only the predictive values of the PSA test induced by the exposure of interest.

Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

Objective: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC).

Patients And Methods: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.

Aligning germline and somatic mutations in prostate cancer. Are genetics changing practice?

Objective: To review the current status of germline and somatic (tumour) genetic testing for prostate cancer (PCa), and its relevance for clinical practice.

Methods: A narrative synthesis of various molecular profiles related to their clinical context was carried out. Current guidelines for genetic testing and its feasibility in clinical practice were analysed.

Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry.

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS.

Dissecting the genetic heterogeneity of gastric cancer.

Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry.

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.

Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.

Design, Setting, And Participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.

Clinical performance of magnetic resonance imaging and biomarkers for prostate cancer diagnosis in men at high genetic risk.

Objectives: To evaluate different scenarios for the management of early diagnosis of cancer (PCa) in men at high genetic risk, using recently developed blood and urinary molecular biomarkers in combination with clinical information alongside multiparametric magnetic resonance imaging (mpMRI).

Patients And Methods: A total of 322 patients with a high genetic risk (familial or personal history of cancers or a predisposing germline variant) were included in this study. The primary outcome was the detection rates of PCa (positive biopsy) or clinically significant PCa (biopsy with International Society of Urological Pathology [ISUP] grade >1).

Functional characterization of 5p15.33 risk locus in uveal melanoma reveals rs452384 as a functional variant and NKX2.4 as an allele-specific interactor.

The TERT/CLPTM1L risk locus on chromosome 5p15.33 is a pleiotropic cancer risk locus in which multiple independent risk alleles have been identified, across well over ten cancer types. We previously conducted a genome-wide association study in uveal melanoma (UM), which uncovered a role for the TERT/CLPTM1L risk locus in this intraocular tumor and identified multiple highly correlated risk alleles.

Rare Germline Variants Are Associated with Rapid Biochemical Recurrence After Radical Prostate Cancer Treatment: A Pan Prostate Cancer Group Study.

Background: Germline variants explain more than a third of prostate cancer (PrCa) risk, but very few associations have been identified between heritable factors and clinical progression.

Objective: To find rare germline variants that predict time to biochemical recurrence (BCR) after radical treatment in men with PrCa and understand the genetic factors associated with such progression.

Design, Setting, And Participants: Whole-genome sequencing data from blood DNA were analysed for 850 PrCa patients with radical treatment from the Pan Prostate Cancer Group (PPCG) consortium from the UK, Canada, Germany, Australia, and France.

DNA damage repair gene germline profiling for metastatic prostate cancer patients of different ancestries.

Background: Germline and somatic mutations in DNA damage repair genes (DDRg) are now recognized as new biomarkers for the management of metastatic prostate cancers (mPC). We evaluate the frequency of germline DDRg mutations among French mPC patients of European and African ancestries.

Methods: Targeted next-generation sequencing of 21 DDRg was performed on germline DNA from 557 mPC patients, including 15.

Screening, diagnosis and monitoring of sarcopenia: When to use which tool?

Background & Aims: Sarcopenia is a muscle disorder associated with loss of muscle mass, strength and function. Early screening, diagnosis and treatment may improve outcome in different disease conditions. A wide variety of tools for estimation of muscle mass is available and each tool has specific technical requirements.

Development and validation of a cell cycle progression signature for decentralized testing of men with prostate cancer.

The 46-gene Prolaris cell cycle progression test provides information on the risk of prostate cancer progression. Here we developed and validated a 16-gene kit-based version. RNA was extracted from prostate cancer biopsy tissue.

A study of the immunohistochemical profile of bladder cancer in neuro-urological patients by the French Association of Urology.

Purpose: To establish whether the expression of markers of cell differentiation (CK7, CK14, CK20, GATA3), apoptosis (p53), proliferation (Ki67, STAG2) and peri-tumoural lymphocytes (CD3, CD8), provides specific information about urothelial carcinogenesis in neuro-urological patients with bladder cancer (NBC).

Methods: Tissue samples from NBC were retrieved from 15 centres in France and compared to control samples from non neuro-urological patients with bladder cancer (NNBC) and from neuro-urological patients without bladder cancer (NB). The expression of CK7, CK14, CK20, GATA3, p53, Ki67, STAG2, CD3 and CD8 markers was analysed using immunohistochemistry of tissue microarray sections.

A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry.

A rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.

Different Pigmentation Risk Loci for High-Risk Monosomy 3 and Low-Risk Disomy 3 Uveal Melanomas.

Background: Uveal melanoma (UM), a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. UMs carrying a monosomy 3 (M3) frequently relapse mainly in the liver, whereas UMs with disomy 3 (D3) are associated with more favorable outcome. Here, we explored the UM genetic predisposition factors in a large genome-wide association study (GWAS) of 1142 European UM patients and 882 healthy controls .