465 results on '"Ferlicot, Sophie"'
Search Results
152. The role of replicative senescence in chronic allograft nephropathy
- Author
-
Ferlicot, Sophie, primary, Durrbach, Antoine, additional, Bâ, Nathalie, additional, Desvaux, Dominique, additional, Bedossa, Pierre, additional, and Paradis, Valérie, additional
- Published
- 2003
- Full Text
- View/download PDF
153. Measurement of telomere length on tissue sections using quantitative fluorescence in situ hybridization (Q‐FISH)
- Author
-
Ferlicot, Sophie, primary, Youssef, Nelly, additional, Feneux, Danielle, additional, Delhommeau, François, additional, Paradis, Valérie, additional, and Bedossa, Pierre, additional
- Published
- 2003
- Full Text
- View/download PDF
154. Gastric Inflammatory Myofibroblastic Tumors in Children: An Unpredictable Course
- Author
-
Lazure, Thierry, primary, Ferlicot, Sophie, additional, Gauthier, Frédéric, additional, Doz, François, additional, Couturier, Jérôme, additional, Fabre, Monique, additional, and Bedossa, Pierre, additional
- Published
- 2002
- Full Text
- View/download PDF
155. Expression of cyclooxygenase 2 and prostaglandin E synthase after renal ischemia-reperfusion
- Author
-
Malika, Ait Ali Slimane, primary, Eschwége, Pascal, additional, Droupy, Stéphane, additional, Conti, Marc, additional, Cosson, Claudine, additional, Paradis, Valérie, additional, Ferlicot, Sophie, additional, Loric, Sylvain, additional, Bedossa, Pierre, additional, Gauthier, Frédéric, additional, and Benoît, Gérard, additional
- Published
- 2002
- Full Text
- View/download PDF
156. hTERT expression in sporadic renal cell carcinomas
- Author
-
Paradis, Valérie, primary, Bièche, Ivan, additional, Dargère, Delphine, additional, Bonvoust, Franck, additional, Ferlicot, Sophie, additional, Olivi, Martine, additional, Ben Lagha, Nadia, additional, Blanchet, Pascal, additional, Benoît, Gérard, additional, Vidaud, Michel, additional, and Bedossa, Pierre, additional
- Published
- 2001
- Full Text
- View/download PDF
157. In situdetection of telomerase enzymatic activity in human hepatocellular carcinogenesis
- Author
-
Youssef, Nelly, primary, Paradis, Valerie, additional, Ferlicot, Sophie, additional, and Bedossa, Pierre, additional
- Published
- 2001
- Full Text
- View/download PDF
158. Intraabdominal Desmoplastic Small Round Cell Tumor
- Author
-
Ferlicot, Sophie, primary, Coué, Olivier, additional, Gilbert, Elisabeth, additional, Beuzeboc, Philippe, additional, Servois, Vincent, additional, Klijanienko, Jerzy, additional, Delattre, Olivier, additional, and Vielh, Philippe, additional
- Published
- 2001
- Full Text
- View/download PDF
159. "Burned-Out" Testicular Tumor: Report of Three Cases
- Author
-
Ferlicot, Sophie, primary, Paradis, Valérie, additional, Ladouch, Aliette, additional, Lagha, Nadia Ben, additional, Eschwège, Pascal, additional, Benoît, Gérard, additional, and Bedossa, Pierre, additional
- Published
- 1999
- Full Text
- View/download PDF
160. Genomic expression and single-nucleotidepolymorphism profiling discriminates chromophoberenal cell carcinoma and oncocytoma.
- Author
-
Min-Han Tan, Chin Fong Wong, Hwei Ling Tan, Yang, Ximing J., Ditlev, Jonathon, Matsuda, Daisuke, Sok Kean Khoo, Jun Sugimura, Fujioka, Tomoaki, Furge, Kyle A., Kort, Eric, Giraud, Sophie, Ferlicot, Sophie, Vielh, Philippe, Amsellem-Ouazana, Delphine, Debré, Bernard, Flam, Thierry, Thiounn, Nicolas, Zerbib, Marc, and Benoît, Gérard
- Subjects
GENETIC polymorphisms ,RENAL cell carcinoma ,GENE expression ,CYSTS (Pathology) ,GENETIC toxicology - Abstract
Background: Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. Methods: Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors. Results: A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. Conclusions: Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
161. In situ detection of telomerase enzymatic activity in human hepatocellular carcinogenesis.
- Author
-
Youssef, Nelly, Paradis, Valerie, Ferlicot, Sophie, and Bedossa, Pierre
- Published
- 2001
- Full Text
- View/download PDF
162. Impact of VKORC1Haplotypes on Long-Term Graft Function in Kidney Transplantation
- Author
-
Quteineh, Lina, Verstuyft, Celine, Durrbach, Antoine, Letierce, Alexia, Ferlicot, Sophie, Charpentier, Bernard, and Becquemont, Laurent
- Abstract
Chronic allograft injury is the major cause of renal allograft loss after the first year of transplantation. Vitamin K epoxide reductase complex subunit 1 (VKORC1) haplotype combinations were found to be associated with the risk of developing vascular diseases. We aimed to study the effect of VKORC1haplotypes on long-term graft function in a cohort of kidney transplant recipients.
- Published
- 2008
- Full Text
- View/download PDF
163. Mucinous tubular and spindle cell carcinoma: a report of 15 cases and a review of the literature
- Author
-
Ferlicot, Sophie, Allory, Yves, Compérat, Eva, Mege-Lechevalier, Florence, Dimet, Stéphanie, Sibony, Mathilde, Couturier, Jérome, and Vieillefond, Annick
- Abstract
Abstract: Mucinous tubular and spindle cell carcinomas are low-grade renal epithelial neoplasms, which were first recognized as a specific entity in the World Health Organization 2004 classification. Forty-five documented cases have been reported. We present 15 additional cases that were incidentally discovered in ten women and five men, with a mean age of 53 years. The tumor is characteristically made up of large eosinophilic regular spindle cells separated by a myxoid stroma with intercellular alcian-blue-positive clear droplets. In peripheral areas, elongated tubules and papillae covered by cubic cells are found. Until this entity had been defined, pathologists used to classify these tumors as variants of solid papillary carcinomas with compressed and elongated papillae, metanephric adenomas, and sarcomatoid carcinomas. In the literature, cytogenetic data indicate various chromosomal losses and gains, but no loss of 3p or trisomy 7 and/or trisomy 17. In two cases, we demonstrate chromosomal loss involving chromosomes 1, 4, 6, 11, 8, 13, 14, 15, 18, and 22. In our 15 cases, immunohistochemistry favored a distal tubule origin (EMA
+ , AE1/AE3+ , CK7+ , CK19+ , E-cadherin+ , AMACR+ , and CD10− ). Prognosis was favorable in our cases, while in the literature, two metastatic cases were reported. Further investigations are required to determine the frequency and true prognosis of these tumors, which are easily identifiable morphologically.- Published
- 2005
- Full Text
- View/download PDF
164. Azoospermia and reciprocal translocation : the two hits hypothesis
- Author
-
Ghieh, Farah, Barbotin, Anne-Laure, Prasivoravong, Julie, Ferlicot, Sophie, Mandon-Pépin, Béatrice, Fortemps, Joanne, Garchon, Henri-Jean, Serazin, Valérie, Leroy, Clara, Marcelli, François, and Vialard, François
- Abstract
L’azoospermie, touchant 1 % des hommes, se traduit par un arrêt méiotique (AM) testiculaire dans 5 % des cas. Bien que l’étiologie de l’AM soit probablement d’origine génétique, seuls quelques anomalies, comme les aberrations chromosomiques, ont été identifiées comme causes récurrentes de ce phénotype testiculaire. Les translocations chromosomiques qu’elles soient réciproques ou robertsoniennes, ont des effets variables sur la spermatogenèse. Par conséquent, aucun marqueur existe pour évaluer le pronostic d’extraction de sperme testiculaire (TESE). L’objectif de cette étude est de définir de nouvelles guidelines pour évaluer la probabilité de TESE positive pour les patients azoospermes présentant des translocations réciproques.
- Published
- 2021
- Full Text
- View/download PDF
165. The Clinicopathological Spectrum of Kidney Lesions in Chikungunya Fever: A Report of 5 Cases With Kidney Biopsy
- Author
-
Aurore, Anne-Claire, Couderc, Thérèse, Dueymes, Jean-Marc, Deligny, Christophe, Lecuit, Marc, Molinié, Vincent, and Ferlicot, Sophie
- Abstract
Chikungunya nephropathy is an uncommon etiology of acute kidney injury, associated with the mosquito-borne Chikungunya arbovirus (CHIKV). The very limited number of pathological reports to date have only involved postmortem analyses. We here report five cases of acute kidney injury for which kidney biopsies were performed in patients with confirmed acute CHIKV infection, during the recent outbreak of Chikungunya disease in the French West Indies. The patients ranged from 42 to 76 years of age. All of the patients developed kidney injury, three of whom required transient kidney dialysis and underwent a kidney biopsy. Analysis of kidney biopsies revealed two main histopathological patterns: acute interstitial nephritis with predominant lymphoid inflammation and acute tubular injury. Epithelioid granulomas were observed in two cases. There were no glomerular lesions, except for two patients including one with a previous known primary focal segmental glomerulosclerosis. CHIKV antigen immunofluorescence microscopy revealed staining in tubular cells. In all of the cases, the short-term outcome was favorable, with recovery of kidney function.
- Published
- 2021
- Full Text
- View/download PDF
166. Severe acute respiratory syndrome coronavirus 2 indirectly damages kidney structures.
- Author
-
Dargelos, Mathilde, Couturier, Aymeric, Ferlicot, Sophie, Goujon, Jean-Michel, Roque-Afonso, Anne-Marie, Gault, Elyanne, Touchard, Guy, Ory, Cecile, Kaaki, Sihem, Vilaine, Eve, Essig, Marie, and Massy, Ziad A
- Subjects
- *
COVID-19 , *ANGIOTENSIN converting enzyme , *RENAL biopsy , *SARS-CoV-2 , *KIDNEYS - Abstract
Background The objectives were to characterize Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) in patients with acute kidney injury (AKI). Methods Kidney biopsy samples in two Caucasian patients and one African with COVID-19 AKI were investigated. Results All patients had a high-level non-selective glomerular proteinuria. SARS-CoV-2 samples by real-time polymerase chain reaction (RT- PCR) assay were all-negative, as well as for virus particles in the kidney by electron microscopy. The three patients and patients with other AKI did not differ significantly with regard to angiotensin-converting enzyme 2 and transmembrane protease serine 2 kidney staining. Conclusions The kidney damage particularly in Caucasians in COVID-19 seems to be an AKI, possibly by the systemic inflammatory response. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
167. Urinary biomarkers for bladder cancer diagnosis and NMIBC follow-up: a systematic review.
- Author
-
Soorojebally, Yanish, Neuzillet, Yann, Roumiguié, Mathieu, Lamy, Pierre-Jean, Allory, Yves, Descotes, Françoise, Ferlicot, Sophie, Kassab-Chahmi, Diana, Oudard, Stéphane, Rébillard, Xavier, Roy, Catherine, Lebret, Thierry, Rouprêt, Morgan, and Audenet, François
- Subjects
- *
BLADDER cancer , *CANCER diagnosis , *NON-muscle invasive bladder cancer , *TUMOR markers , *BLADDER , *TRANSURETHRAL resection of bladder - Abstract
Background: Bladder cancer detection and follow-up is based on cystoscopy and/or cytology, but it remains imperfect and invasive. Current research focuses on diagnostic biomarkers that could improve bladder cancer detection and follow-up by discriminating patients at risk of aggressive cancer who need confirmatory TURBT (Transurethral Resection of Bladder Tumour) from patients at no risk of aggressive cancer who could be spared from useless explorations. Objective: To perform a systematic review of data on the clinical validity and clinical utility of eleven urinary biomarkers (VisioCyt®, Xpert®Bladder, BTA stat®, BTA TRAK™, NMP22 BC®, NMP22® BladderChek® Test, ImmunoCyt™/uCyt1+™, UroVysion Bladder Cancer Kit®, Cxbladder, ADXBLADDER, Urodiag®) for bladder cancer diagnosis and for non-muscle invasive bladder cancer (NMIBC) follow-up. Methods: All available studies on the 11 biomarkers published between May 2010 and March 2021 and present in MEDLINE® were reviewed. The main endpoints were clinical performance for bladder cancer detection, recurrence or progression during NMIBC monitoring, and additional value compared to cytology and/or cystoscopy. Results: Most studies on urinary biomarkers had a prospective design and high level of evidence. However, their results should be interpreted with caution given the heterogeneity among studies. Most of the biomarkers under study displayed higher detection sensitivity compared with cytology, but lower specificity. Some biomarkers may have clinical utility for NMIBC surveillance in patients with negative or equivocal cystoscopy or negative or atypical urinary cytology findings, and also for recurrence prediction. Conclusion: Urinary biomarkers might have a complementary place in bladder cancer diagnosis and NMIBC surveillance. However, their clinical benefit remains to be confirmed. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
168. Cryptic splice site poisoning and meiotic arrest caused by a homozygous frameshift mutation in RBMXL2: A case report.
- Author
-
Ghieh, Farah, Izard, Vincent, Poulain, Marine, Fortemps, Johanne, Kazdar, Nadia, Mandon‐Pepin, Béatrice, Ferlicot, Sophie, Ayoubi, Jean Marc, and Vialard, François
- Subjects
- *
FRAMESHIFT mutation , *ALTERNATIVE RNA splicing , *MALE infertility , *RNA-binding proteins , *KNOCKOUT mice , *POISONING - Abstract
Gene expression in meiotic cells in the testis is characterized by intense transcriptional activity and alternative splicing. These processes are mainly controlled by RNA‐binding proteins expressed strongly in germ cells. Functional impairments in any of these proteins' functions can lead to defects in meiosis and thus severe male infertility. Here, we have identified a homozygous frameshift mutation (NM_014469.4:c.301dup; p.Ser101LysfsTer29) in the RNA‐binding motif protein, X‐linked like 2 (RBMXL2) gene in a man with an azoospermia due to meiotic arrest. As RBMXL2 is known to be crucial for safeguarding the meiotic transcriptome in mice testes, we hypothesized that this variant leads to cryptic splice site poisoning. To determine the variant's impact on spermatogenesis, we confirmed the absence of RBMXL2 protein in the patient's testis tissue and then evidenced abnormal expression of several spermatogenesis proteins (e.g. meiosis‐specific with coiled‐coil domain) known to be altered in rbmxl2 knock‐out mice with meiotic arrest. Our results indicate that RBMXL2's function in spermatogenesis is conserved in mammals. We hypothesize that deleterious variant in the RBMXL2 gene can result in male infertility and complete meiotic arrest, due to the disruption of gene expression by cryptic splice site poisoning. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
169. Ultrasound and Magnetic Resonance Imaging of Burned-Out Testicular Tumours: The Diagnostic Keys Based on 48 Cases.
- Author
-
Desmousseaux, Thomas, Arama, Emmanuel, Maxwell, Florian, Ferlicot, Sophie, Hani, Chahinez, Fizazi, Karim, Lebacle, Cédric, Loriot, Yohann, Boumerzoug, Meriem, Cohen, Julian, Garrouche, Nada, and Rocher, Laurence
- Subjects
- *
RETROPERITONEUM , *MAGNETIC resonance imaging , *METASTASIS , *RETROSPECTIVE studies , *ACQUISITION of data , *MANN Whitney U Test , *FISHER exact test , *CANCER patients , *T-test (Statistics) , *TESTIS tumors , *SCROTUM , *HISTOLOGICAL techniques , *CASTRATION , *DESCRIPTIVE statistics , *MEDICAL records , *DATA analysis software - Abstract
Simple Summary: In rare cases, testicular cancers regress spontaneously. This is known as a burned-out testicular tumour. Few data have been published regarding the radiological appearance of these lesions. In this study, we describe the lesions observed in 48 patients using several imaging techniques (conventional ultrasound, advanced ultrasound techniques and MRI). In both ultrasound and MRI, there are features that allow the recognition of such lesions and may help in the correct management of these patients by proposing orchiectomy. The spontaneous regression of testicular germ-cell tumours is a rare event whose mechanisms have yet to be elucidated. In the majority of published cases, tumour regression is concomitant with the metastatic development of the disease. Residual lesions, often referred to as burned-out testicular tumours (BOTTs), are difficult to diagnose due to the paucity of published data, especially in the field of imaging. The aim of this article is to describe the radiological signs of BOTTs on multimodal ultrasound and multiparametric MRI from a series of 48 patients whose diagnosis was confirmed histologically. The demographic, clinical and laboratory characteristics of the patients are studied, as well as the data of the imaging examinations, including conventional scrotal ultrasound, shear-wave elastography, contrast-enhanced ultrasound (CEUS) and multiparametric MRI. A total of 27 out of 48 patients were referred for investigation of primary testicular lesion following the discovery of retroperitoneal metastases, 18/48 patients were referred because of lesions suspected on an ultrasound that was performed for an infertility work-up, and 3/48 were referred because of scrotal clinical signs. Of these last 21 patients (infertility work-up/scrotal clinical sign), 6 were found to be metastatic on the extension work-up. Of the 48 orchiectomy specimens, tumour involution was complete in 41 cases, and a small active contingent remained in 7 cases, with 6 suspected upon advanced US and MRI. Typically, BOTTs appear on a conventional ultrasound as ill-delineated, hypoechoic and hypovascular nodular areas. Clustered microliths (60.4%) and macrocalcifications (35.4%) were frequent. Shear-wave elastography showed areas of focal induration (13.5 ± 8.4 vs. 2.7 ± 1.2 kPa for normal parenchyma, p < 0.01) in 92.5% of the patients for whom it was performed, and contrast ultrasonography demonstrated hypoperfusion of these lesions. Of the 42 MRIs performed, BOTTs corresponded to nodules on T2-weighted sequences (hyposignal) with significantly increased ADC values compared with healthy parenchyma (2 ± 0.3 versus 1.3 ± 0.3 × 10−3 mm2/s, p < 0.01) and an enhancement defect after injection. This enhancement defect overlapped the lesions visible on T2-weighted sequences in most cases. In the case of predominant partial regression, an enhanced portion after contrast injection was visible on MRI in all seven patients of our series, and in six of them a focal diffusion restriction zone was also present. Spontaneously involuted testicular germ-cell tumours have specific radiological signs, and all of the mentioned examinations contribute to this difficult diagnosis, even histologically, because there is no tumour cell left. These signs are similar whether the patient is initially symptomatic metastatic or whether the discovery is fortuitous on the occasion of an infertility work-up, and whatever the seminomatous or non-seminomatous nature of the germ-cell tumour, when this can be determined. The appearance of regressed germ-cell tumours is often trivialized, which can lead to the wrong diagnosis of an extra gonadal germ-cell tumour (in metastatic patients) or of scarring from an acute event such as trauma or infection, which is not recognized or forgotten. In our series, two patients had an unrecognized diagnosis in their history, with local and/or distant recurrence. An improvement in diagnosing burned-out tumours, combining advanced US and MRI, is necessary in order to optimize patient management, with special attention paid to asymptomatic patients, to prompt extension screening and orchiectomy with analysis of the whole testis. This may reveal a persistent viable tumour or lesions of germinal neoplasia in situ, which are precursors of testicular germ-cell tumours. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
170. Testicular Lesions in Infertile Men.
- Author
-
Dupeux, Margot, Maxwell, Florian, Rocher, Laurence, Izard, Vincent, Guettier, Catherine, and Ferlicot, Sophie
- Subjects
- *
GERMINOMA , *GENITALIA tumors , *RETROSPECTIVE studies , *INFERTILITY , *TESTIS tumors , *DISEASE complications - Abstract
Objectives: An increasing number of incidental testicular tumors are diagnosed in patients during infertility workup. The aim of this study was to evaluate the accuracy of frozen section examination (FSE) for the management of these tumors.Methods: We retrospectively studied a series of 46 testicular tumors diagnosed during exploration for infertility from 2000 to 2019 and submitted for FSE.Results: A diagnosis of malignancy was made in 23 cases on both gross examination (yellow-white or cream-colored nodules for seminomas) and FSE, then confirmed on final diagnosis in 22 of the cases. One seminoma reported on FSE was revised as being a Leydig cell tumor. The 23 other lesions were diagnosed as benign on FSE, including 11 Leydig cell tumors (yellow-brown nodules), 2 Leydig cell hyperplasias, and 10 whitish fibrous lesions. All Leydig cell lesions were confirmed except 1, which was reclassified as a Sertoli cell tumor. Of the 10 cases of fibrous lesions, 6 were associated with malignancy.Conclusions: The high incidence of Leydig cell tumors and the accuracy of FSE for these lesions demonstrate the interest in FSE. In contrast, FSE is not reliable for fibrous lesions, and surgeons should be aware that a fibrosis result often corresponds with regressed tumors. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
171. DCLRE1B/Apollo germline mutations associated with renal cell carcinoma impair telomere protection.
- Author
-
Bories, Charlie, Lejour, Thomas, Adolphe, Florine, Kermasson, Laëtitia, Couvé, Sophie, Tanguy, Laura, Luszczewska, Gabriela, Watzky, Manon, Poillerat, Victoria, Garnier, Pauline, Groisman, Regina, Ferlicot, Sophie, Richard, Stéphane, Saparbaev, Murat, Revy, Patrick, Gad, Sophie, and Renaud, Flore
- Subjects
- *
RENAL cell carcinoma , *TELOMERES , *GERM cells , *DNA repair , *CELLULAR aging , *MISSENSE mutation , *GENETIC mutation - Abstract
Hereditary renal cell carcinoma (RCC) is caused by germline mutations in a subset of genes, including VHL , MET , FLCN , and FH. However, many familial RCC cases do not harbor mutations in the known predisposition genes. Using Whole Exome Sequencing, we identified two germline missense variants in the DCLRE1B/Apollo gene (Apollo N246I and Apollo Y273H ) in two unrelated families with several RCC cases. Apollo encodes an exonuclease involved in DNA Damage Response and Repair (DDRR) and telomere integrity. We characterized these two functions in the human renal epithelial cell line HKC8. The decrease or inhibition of Apollo expression sensitizes these cells to DNA interstrand crosslink damage (ICLs). HKC8 Apollo −/− cells appear defective in the DDRR and present an accumulation of telomere damage. Wild-type and mutated Apollo forms could interact with TRF2, a shelterin protein involved in telomere protection. However, only ApolloWT can rescue the telomere damage in HKC8 Apollo −/− cells. Our results strongly suggest that ApolloN246I and ApolloY273H are loss-of-function mutants that cause impaired telomere integrity and could lead to genomic instability. Altogether, our results suggest that mutations in Apollo could induce renal oncogenesis. [Display omitted] • Two germline mutations in DCLRE1B/Apollo in two families with inherited ccRCC • Inhibition of Apollo sensitized HKC8 cells to DNA damages • ApolloWT protects telomeres by contrast to ApolloN246I and ApolloY273H • Apollo mutants could lead to genomic instability and renal oncogenesis • Putative link between DNA repair, telomere protection and renal oncogenesis [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
172. High-flow Priapism Due to a Malignant Glomus Tumor (Glomangiosarcoma) of the Corpus Cavernosum.
- Author
-
Masson-Lecomte, Alexandra, Rocher, Laurence, Ferlicot, Sophie, Benoît, Gérard, and Droupy, Stéphane
- Subjects
- *
PRIAPISM , *WOUNDS & injuries , *BLOOD vessels , *PENILE tumors , *TUMORS , *IMPOTENCE - Abstract
ABSTRACT Introduction. The major cause of non-ischemic high-flow priapism is post-traumatic vascular injury leading to an arterio-lacunar fistula. However, rare causes such as tumors may induce priapism. This is the first report of a malignant glomus tumor localized in the corpora cavernosa. Aim. The aim of this case is to emphasize the importance of the initial management of priapism and to suggest new tracks on the tests to be performed when the usual exams are not sufficient. Method. We report the case of a hypervascular penile tumor responsible for high-flow priapism as the first clinical symptom of a metastatic glomus tumor. The persistent penile tumescence was initially considered to be a stuttering priapism and treated using an oral α-adrenergic as no provoking event nor fistula was found. After a 2-week reluctance, a penile magnetic resonance imaging (MRI) was performed. Results. The MRI showed a hypervascular lesion at the proximal part of the right corpora. The lesion was considered as a fistula, and a selective embolization was performed. Two weeks after embolization, the patient came back to the emergency room because of syncopes and dyspnea. Examination by cardiac ultrasound and chest computed tomography revealed the presence of cardiac, pulmonary, and subcutaneous malignant glomus tumors (glomangiosarcoma). Patient received three lines of chemotherapy, and the penile tumor was surgically removed because of persistent erectile dysfunction and perineal pain. Conclusion. This case supports the use of corporal body blood gas analysis in difficult cases to discriminate high- and low-flow priapism and penile MRI when clinical history, physical examination, and aspiration are not contributory. Masson-Lecomte A, Rocher L, Ferlicot S, Benoît G, and Droupy S. High-flow priapism due to a malignant glomus tumor (glomangiosarcoma) of the corpus cavernosum. J Sex Med **;**:**-**. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
173. IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?
- Author
-
Devocelle, Aurore, Lecru, Lola, Ferlicot, Sophie, Bessede, Thomas, Candelier, Jean-Jacques, Giron-Michel, Julien, and François, Hélène
- Subjects
- *
RENAL fibrosis , *CHRONIC kidney failure , *MYOFIBROBLASTS , *MONOCYTE chemotactic factor , *COLLAGEN , *EXTRACELLULAR matrix , *FIBRONECTINS , *TRANSFORMING growth factors - Abstract
Chronic kidney disease (CKD), secondary to renal fibrogenesis, is a public health burden. The activation of interstitial myofibroblasts and excessive production of extracellular matrix (ECM) proteins are major events leading to end-stage kidney disease. Recently, interleukin-15 (IL-15) has been implicated in fibrosis protection in several organs, with little evidence in the kidney. Since endogenous IL-15 expression decreased in nephrectomized human allografts evolving toward fibrosis and kidneys in the unilateral ureteral obstruction (UUO) model, we explored IL-15's renoprotective role by pharmologically delivering IL-15 coupled or not with its soluble receptor IL-15Rα. Despite the lack of effects on myofibroblast accumulation, both IL-15 treatments prevented tubulointerstitial fibrosis (TIF) in UUO as characterized by reduced collagen and fibronectin deposition. Moreover, IL-15 treatments inhibited collagen and fibronectin secretion by transforming growth factor-β (TGF-β)-treated primary myofibroblast cultures, demonstrating that the antifibrotic effect of IL-15 in UUO acts, in part, through a direct inhibition of ECM synthesis by myofibroblasts. In addition, IL-15 treatments resulted in decreased expression of monocyte chemoattractant protein 1 (MCP-1) and subsequent macrophage infiltration in UUO. Taken together, our study highlights a major role of IL-15 on myofibroblasts and macrophages, two main effector cells in renal fibrosis, demonstrating that IL-15 may represent a new therapeutic option for CKD. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
174. Technical feasibility and correlations between shear-wave elastography and histology in kidney fibrosis in children.
- Author
-
Desvignes, Catherine, Dabadie, Alexia, Aschero, Audrey, Ruocco, Alix, Garaix, Florentine, Daniel, Laurent, Ferlicot, Sophie, Villes, Virginie, Loundou, Anderson D., Gorincour, Guillaume, and Petit, Philippe
- Subjects
- *
RENAL fibrosis , *KIDNEY transplantation , *HISTOLOGY , *RENAL biopsy , *ELASTOGRAPHY , *JUVENILE diseases - Abstract
Background: Ultrasound elastography has been suggested for assessing organ fibrosis. Objective: To study the feasibility of shear-wave elastography in children with kidney disease and the correlation between elasticity and kidney fibrosis in order to reduce the indications for kidney biopsy and its complications. Materials and methods: Four operators measured kidney elasticity in children with kidney diseases or transplants, all of whom also had a renal biopsy. We assessed the feasibility and the intraobserver variability of the elasticity measurements for each probe used and each kidney explored. Then we tested the correlation between elasticity measurements and the presence of fibrosis. Results: Overall, we analyzed 95 children and adolescents, 31 of whom had renal transplant. Measurements with the convex probe were possible in 100% of cases. Linear probe analysis was only possible for 20% of native kidneys and 50% of transplants. Intraobserver variabilities ranged from moderate to high, depending on the probe and kidney studied. Elasticity was higher with the linear probe than with the convex probe (P<0.001 for left kidney and P=0.03 for right kidney). Measurements did not differ from one kidney to another in the same child. Elasticity and fibrosis were both higher in transplant patients (P=0.02 with convex probe; P=0.01 with linear probe; P=0.04 overall). There was no correlation between elasticity and fibrosis. Conclusion: Of the devices used in this work, kidney elastography was more accurately analyzed with a convex probe. Our study did not identify any correlation between elasticity and kidney fibrosis. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
175. Long‐term exposure to monoclonal anti‐TNF is associated with an increased risk of lymphoma in BAFF‐transgenic mice.
- Author
-
Nocturne, Gaetane, Ly, Bineta, Paoletti, Audrey, Pascaud, Juliette, Seror, Raphaele, Nicco, Carole, Mackay, Fabienne, Vincent, F.B., Lazure, Thierry, Ferlicot, Sophie, Stimmer, Lev, Pascal, Quentin, Roulland, Sandrine, Krzysiek, Roman, Hacein‐Bey, Salima, Batteux, Frederic, and Mariette, Xavier
- Subjects
- *
TUMOR necrosis factors , *LYMPHOMAS , *MONOCLONAL antibodies , *TUMOR necrosis factor receptors , *SPLEEN - Abstract
Summary: The impact of treatment on the risk of lymphoma in patients with rheumatoid arthritis (RA) is unclear. Here, we aimed to assess if the risk of lymphoma differs according to the type of tumor necrosis factor inhibitor (TNFi), comparing monoclonal anti‐TNF antibodies to the soluble TNF receptor. We used B cell activating factor belonging to the TNF family (BAFF)‐transgenic (Tg) mice as a model of autoimmunity‐associated lymphoma. Six‐month‐old BAFF‐Tg mice were treated with TNFi for 12 months. Histological examination of the spleen, assessment of the cellular composition of the spleen by flow cytometry and assessment of B cell clonality were performed at euthanasia. Crude mortality and incidence of lymphoma were significantly higher in mice treated with monoclonal anti‐TNF antibodies compared to both controls and mice treated with the soluble TNF receptor, even at a high dose. Flow cytometry analysis revealed decreased splenic macrophage infiltration in mice treated with monoclonal anti‐TNF antibodies. Overall, this study demonstrates, for the first time, that a very prolonged treatment with monoclonal anti‐TNF antibodies increase the risk of lymphoma in B cell‐driven autoimmunity. These data suggest a closer monitoring for lymphoma development in patients suffering from B cell‐driven autoimmune disease with long‐term exposure to monoclonal anti‐TNF antibodies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
176. Ultrasound Molecular Imaging of Renal Cell Carcinoma: VEGFR targeted therapy monitored with VEGFR1 and FSHR targeted microbubbles.
- Author
-
Ingels, Alexandre, Leguerney, Ingrid, Cournède, Paul-Henry, Irani, Jacques, Ferlicot, Sophie, Sébrié, Catherine, Benatsou, Baya, Jourdain, Laurène, Pitre-Champagnat, Stephanie, Patard, Jean-Jacques, and Lassau, Nathalie
- Subjects
- *
RENAL cell carcinoma , *IMMUNOTHERAPY , *PROTEIN-tyrosine kinase inhibitors , *MICROBUBBLES , *ULTRASONIC imaging , *LABORATORY mice - Abstract
Recent treatment developments for metastatic renal cell carcinoma offer combinations of immunotherapies or immunotherapy associated with tyrosine kinase inhibitors (TKI). There is currently no argument to choose one solution or another. Easy-to-use markers to assess longitudinal responses to TKI are necessary to determine when to switch to immunotherapies. These new markers will enable an earlier adaptation of therapeutic strategy in order to prevent tumor development, unnecessary toxicity and financial costs. This study evaluates the potential of ultrasound molecular imaging to track the response to sunitinib in a clear cell renal carcinoma model (ccRCC). We used a patient-derived xenograft model for this imaging study. Mice harboring human ccRCC were randomized for sunitinib treatment vs. control. The tumors were imaged at days 0, 7, 14 and 28 with ultrasound molecular imaging. Signal enhancement was quantified and compared between the two groups after injections of non-targeted microbubbles and microbubbles targeting VEGFR1 and FSHR. The tumor growth of the sunitinib group was significantly slower. There was a significantly lower expression of both VEGFR-1 and FSHR molecular ultrasound imaging signals in the sunitinib group at all times of treatment (Days 7, 14 and 28). These results confirm the study hypothesis. There was no significant difference between the 2 groups for the non-targeted microbubble ultrasound signal. This study demonstrated for the first time the potential of VEGFR1 and FSHR, by ultrasound-based molecular imaging, to follow-up the longitudinal response to sunitinib in ccRCC. These results should trigger developments for clinical applications. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
177. Usefulness of morphometric image analysis with Sirius Red to assess interstitial fibrosis after renal transplantation from uncontrolled circulatory death donors.
- Author
-
Dao, Myriam, Pouliquen, Christelle, Duquesne, Alyette, Posseme, Katia, Mussini, Charlotte, Durrbach, Antoine, Guettier, Catherine, François, Hélène, and Ferlicot, Sophie
- Subjects
- *
PULMONARY fibrosis , *KIDNEY transplantation , *MORPHOMETRICS , *DEATH , *TRANSPLANTATION of organs, tissues, etc. - Abstract
Early interstitial fibrosis (IF) correlates with long-term renal graft dysfunction, highlighting the need for accurate quantification of IF. However, the currently used Banff classification exhibits some limitations. The aim of our study was to precisely describe the progression of IF after renal transplantation using a new morphometric image analysis method relying of Sirius Red staining. The morphometric analysis we developed showed high inter-observer and intra-observer reproducibility, with ICC [95% IC] of respectively 0.75 [0.67–0.81] (n = 151) and 0.88 [0.72–0.95] (n = 21). We used this method to assess IF (mIF) during the first year after the kidney transplantation from 66 uncontrolled donors after circulatory death (uDCD). Both mIF and interstitial fibrosis (ci) according to the Banff classification significantly increased the first three months after transplantation. From M3 to M12, mIF significantly increased whereas Banff classification failed to highlight increase of ci. Moreover, mIF at M12 (p = 0.005) correlated with mean time to graft function recovery and was significantly associated with increase of creatininemia at M12 and at last follow-up. To conclude, the new morphometric image analysis method we developed, using a routine and cheap staining, may provide valuable tool to assess IF and thus to evaluate new sources of grafts. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
178. Characterization of Testicular Masses in Adults: Performance of Combined Quantitative Shear Wave Elastography and Conventional Ultrasound.
- Author
-
Rocher, Laurence, Criton, Aline, Gennisson, Jean-Luc, Creze, Maud, Albiges, Laurence, Ferlicot, Sophie, Bellin, Marie-France, Izard, Vincent, and Correas, Jean-Michel
- Subjects
- *
ELASTOGRAPHY , *CANCER , *MUCINOUS adenocarcinoma , *CYSTS (Pathology) , *LEYDIG cell tumors , *TUMORS - Abstract
We prospectively evaluated the performance of combined shear wave elastography (SWE) and conventional ultrasound (US) for the characterization of 89 testicular focal masses. Testes were evaluated with B-mode, color Doppler and SWE measurements, locating a region of interest on the normal and pathologic parenchyma. Thirty-seven malignant tumors (MTs), 12 burned out tumors (BOTs), 28 Leydig cell tumors (LCTs), 2 dermoid cysts and other benign lesions were included. MTs + BOTs exhibited more microliths and macrocalcifications compared with benign lesions (p < 10-4). LCTs manifested mostly a dominant peripheral vascularization pattern compared with other lesions. MTs + BOTs were stiffer compared with benign lesions (p < 2 × 10-4) but with a moderate area under the receiver operating characteristic curve (AUROC) of 80%. By focusing on LCTs versus MTs + BOTs, diagnostic performance led to an AUROC of 89% for the best stiffness parameter. For combined conventional US and SWE, the diagnostic performance to differentiate all benign lesions versus MTs + BOTs and LCTs versus MTs + BOTs increased to AUROCs of 93% and 98%, respectively. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
179. Testicular Shear Wave Elastography in Normal and Infertile Men: A Prospective Study on 601 Patients.
- Author
-
Rocher, Laurence, Criton, Aline, Gennisson, Jean-Luc, Izard, Vincent, Ferlicot, Sophie, Tanter, Mickael, Benoit, Gerard, Bellin, Marie France, and Correas, Jean-Michel
- Subjects
- *
ELASTOGRAPHY , *MALE infertility , *KLINEFELTER'S syndrome , *VARICOCELE , *TESTIS physiology , *DIAGNOSIS , *INFERTILITY , *LONGITUDINAL method , *TESTIS , *ULTRASONIC imaging ,RESEARCH evaluation - Abstract
Our aim in the study described here was to prospectively establish the feasibility of using and reproducibility of testicular shear-wave elastography in the assessment of testicular stiffness in 62 normal patients and 539 infertile men with obstructive azoospermia (OA), non-Klinefelter syndrome non-obstructive azoospermia (non-KS NOA), Klinefelter syndrome NOA (KS NOA), oligoasthenoteratozoospermia (OAT) or a left varicocele. The feasibility rate was 96.9%, with an intra-class correlation coefficient of 0.85 (95% confidence interval: 0.83-0.88). Median stiffness (interquartile range) values were 2.4 kPa (2.0, 2.9), 2.1 kPa (1.8, 2.5), 2.4 kPa (2.0, 2.7), 2.0 kPa (1.7, 2.4), 2.6 kPa (2, 3.2) and 2.2 kPa (1.8, 2.6) for men with a normal testis (n = 108), OAT (n = 689), OA (n = 119), non-KS NOA (n = 183), KS NOA (n = 70) and varicocele (n = 132), respectively. Testicular shear wave elastography is a feasible and reproducible technique. A significant positive association was found between stiffness and testis volume (p = 0.001). Testicular stiffness was higher in OA than in non-KS NOA populations (p = 1.e-10) and in KS NOA than in NOA populations (p = 2.0e-8), but the substantial number of overlapping values limited the clinical impact. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
180. Poussée lupique sévère chez un homme de 76 ans suivi pour un syndrome de Gougerot-Sjögren primaire dans les suites d'une infection à COVID-19.
- Author
-
Roger, Guillaume, Pavot, Arthur, Bonnet, Isabelle, Ferlicot, Sophie, and Mariette, Xavier
- Published
- 2022
- Full Text
- View/download PDF
181. Testis ultrasound in Klinefelter syndrome infertile men: making the diagnosis and avoiding inappropriate management.
- Author
-
Rocher, Laurence, Moya, Loris, Correas, Jean, Mutuon, Pierre, Ferlicot, Sophie, Young, Jacques, Izard, Vincent, Benoit, Gérard, Brailly-Tabard, Sylvie, and Bellin, Marie
- Subjects
- *
COLOR Doppler ultrasonography , *TESTICULAR diseases , *KLINEFELTER'S syndrome , *HYPOGONADISM , *SEX chromosome abnormalities , *DOPPLER ultrasonography , *FOLLICLE-stimulating hormone - Abstract
Objective: To compare the testicular Color Doppler ultrasound (US), hormone levels, and histological results from 67 infertile men with Klinefelter syndrome (KS), vs. 66 non-KS non-obstructive azoospermic men. Methods: Scrotal US images were collected from 67 infertile KS and 66 non-obstructive, non-KS azoospermic men. The testis volume, echotexture, vascularity, and microliths were evaluated and graded. We defined the following echo pattern alteration groups: normal, striated, coarse, and measurable nodules. The vascularization was classified as low, normal, moderate, or strong. Testosterone, follicle-stimulating hormone, luteinizing hormone, and inhibin B levels were determined. Large testicular nodules were removed. A testicular biopsy and sperm extraction was performed in 18 of the KS, and all of the 66 non-KS men. Results: The mean testis volume was low in the KS, compared to the non-KS patients: i.e., 2 vs. 8 mL ( P < 0.0001). The distributions in the echotexture groups differed markedly, with coarse or nodular patterns in the KS men, and normal/striated patterns in the control patients ( P < 0.0001). The vascularization and microlithiasis grades were higher in the KS patients than the control men ( P < 0.0001 and P < 0.001, respectively). All of the nodules removed from the KS patients were benign Leydig cell tumors, and all of the biopsies showed marked Leydig cell hyperplasia, with spermatogenesis in only two patients. The non-KS biopsies were predominantly Sertoli cell-only syndrome. Conclusions: Small testes, with a coarse or nodular echotexture, hypervascularization, and microlithiasis are associated with KS. The KS nodules were benign Leydig cell tumors/hyperplasias. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
182. Phenotypic switch from non-active primary Sjögren's syndrome to severe systemic Lupus erythematosus after COVID-19 infection in an elderly man.
- Author
-
Roger, Guillaume, Pavot, Arthur, Bonnet, Isabelle, Ferlicot, Sophie, and Mariette, Xavier
- Subjects
- *
SJOGREN'S syndrome , *COVID-19 , *OLDER men , *PHENOTYPES , *KIDNEY glomerulus diseases , *SYSTEMIC lupus erythematosus - Abstract
• We report a phenotypic switch from quiescent primary Sjögren's syndrome to severe systemic Lupus erythematosus in an elderly man after COVID-19 infection. • This case presents an histopathological evidence of immune complex glomerular disease. • This case illustrates that autoantibodies should be monitored in case of rheumatic manifestation during and after COVID-19 infection. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
183. Involvement of PBRM1 in VHL disease-associated clear cell renal cell carcinoma and its putative relationship with the HIF pathway.
- Author
-
Gad, Sophie, Le Teuff, Gwenaël, Nguyen, Baptiste, Verkarre, Virginie, Duchatelle, Veronique, Molinie, Vincent, Posseme, Katia, Grandon, Benjamin, Da Costa, Melanie, Job, Bastien, Meurice, Guillaume, Droin, Nathalie, Mejean, Arnaud, Couve, Sophie, Renaud, Flore, Gardie, Betty, Teh, Bin Tean, Richard, Stephane, and Ferlicot, Sophie
- Subjects
- *
VON Hippel-Lindau disease , *RENAL cell carcinoma , *TUMOR suppressor genes , *SOMATIC mutation , *GENETIC mutation , *TUMOR classification - Abstract
Von Hippel-Lindau (VHL) disease is the main cause of inherited clear-cell renal cell carcinoma (ccRCC) and is caused by germline mutations in the VHL tumor suppressor gene. Bi-allelic VHL alterations lead to inactivation of pVHL, which plays a major role by downstream activation of the hypoxia inducible factor (HIF) pathway. Somatic VHL mutations occur in 80% of sporadic ccRCC cases and the second most frequently mutated gene is polybromo 1 (PBRM1). As there is currently no data regarding PBRM1 involvement in VHL disease-associated ccRCC, the aim of the present study was to assess the PBRM1 mutational status, and PBRM1 and HIF expression in VHL disease-associated ccRCC series compared with a sporadic series. PBRM1 gene was screened by Sanger sequencing for 23 VHL-disease-associated ccRCC and 22 sporadic ccRCC cases. Immunohistochemical studies were performed to detect the expression of PBRM1, HIF1 and HIF2 for all cases. In VHL-associated tumors, 13.0% (n=3/23) had PBRM1 somatic mutations and 17.4% (n=4/23) had a loss of PBRM1 nuclear expression. In sporadic cases, 27.3% (n=6/22) showed PBRM1 somatic mutations and 45.5% (n=10/22) had a loss of PBRM1 nuclear expression. Loss of PBRM1 was associated with an advanced tumor stage. HIF1-positive tumors were observed more frequently in the VHL-associated ccRCC than in the sporadic series. Furthermore, in the VHL cohort, PBRM1 expression appeared to be associated more with HIF1 than with HIF2. Given that hereditary tumors tend to be less aggressive, these results would suggest that co-expression of PBRM1 and HIF1 may have a less oncogenic role in VHL-associated ccRCC. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
184. Congenital Anerythremic Erythroleukemia Presenting as Hepatic Failure.
- Author
-
Lazure, Thierry, Beauchamp, Anne, Croisille, Laure, Ferlicot, Sophie, Feneux, Danielle, and Fabre, Monique
- Subjects
- *
GENETIC disorders , *ERYTHROBLASTOSIS fetalis , *PEDIATRIC hematology , *LIVER failure , *BIOMARKERS , *DIFFERENTIAL diagnosis - Abstract
We report an atypical case of congenital erythroleukemia in a child born with hepatosplenomegaly and abnormal liver tests. The initial peripheral blood cell count showed anemia and hyperleukocytosis with erythroblastosis that disappeared 1 week later. During the next 5 weeks, no blasts were found in the blood, and less than 5% were found on 2 successive bone marrow aspirates. The infant died of hepatic failure. The suspected diagnosis on a premortem liver biopsy was confirmed by an autopsy that showed a blastic infiltration in many organs. These cells expressed only erythroid markers glycophorin A and C. Rearrangement of the myeloid lymphoid leukemia gene was not found by fluorescence in situ hybridization. The main differential diagnoses include metabolic diseases, Langerhans histiocytosis, Pepper syndrome, transient myeloproliferative disorder, and leukemoid reactions. Although some of these can be excluded by the pathologist, others require a multidisciplinary confrontation: clinical, biologic, genetic, and pathologic examinations. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
185. Geographic variation of mutagenic exposures in kidney cancer genomes.
- Author
-
Senkin S, Moody S, Díaz-Gay M, Abedi-Ardekani B, Cattiaux T, Ferreiro-Iglesias A, Wang J, Fitzgerald S, Kazachkova M, Vangara R, Le AP, Bergstrom EN, Khandekar A, Otlu B, Cheema S, Latimer C, Thomas E, Atkins JR, Smith-Byrne K, Cortez Cardoso Penha R, Carreira C, Chopard P, Gaborieau V, Keski-Rahkonen P, Jones D, Teague JW, Ferlicot S, Asgari M, Sangkhathat S, Attawettayanon W, Świątkowska B, Jarmalaite S, Sabaliauskaite R, Shibata T, Fukagawa A, Mates D, Jinga V, Rascu S, Mijuskovic M, Savic S, Milosavljevic S, Bartlett JMS, Albert M, Phouthavongsy L, Ashton-Prolla P, Botton MR, Silva Neto B, Bezerra SM, Curado MP, Zequi SC, Reis RM, Faria EF, de Menezes NS, Ferrari RS, Banks RE, Vasudev NS, Zaridze D, Mukeriya A, Shangina O, Matveev V, Foretova L, Navratilova M, Holcatova I, Hornakova A, Janout V, Purdue MP, Rothman N, Chanock SJ, Ueland PM, Johansson M, McKay J, Scelo G, Chanudet E, Humphreys L, de Carvalho AC, Perdomo S, Alexandrov LB, Stratton MR, and Brennan P
- Subjects
- Female, Humans, Male, Aristolochic Acids adverse effects, Genome, Human genetics, Genomics, Hypertension epidemiology, Incidence, Japan epidemiology, Obesity epidemiology, Risk Factors, Romania epidemiology, Serbia epidemiology, Thailand epidemiology, Tobacco Smoking adverse effects, Tobacco Smoking genetics, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell epidemiology, Carcinoma, Renal Cell chemically induced, Environmental Exposure adverse effects, Environmental Exposure analysis, Geography, Kidney Neoplasms genetics, Kidney Neoplasms epidemiology, Kidney Neoplasms chemically induced, Mutagens adverse effects, Mutation
- Abstract
International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden
1 . In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2 . Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
186. Bone Marrow Oxalosis.
- Author
-
d'Izarny-Gargas T, Dang J, Grünenwald A, Mechref Z, Besson FL, Ferlicot S, and Zaidan M
- Published
- 2024
- Full Text
- View/download PDF
187. Immune checkpoints are predominantly co-expressed by clonally expanded CD4 + FoxP3 + intratumoral T-cells in primary human cancers.
- Author
-
Bredel D, Tihic E, Mouraud S, Danlos FX, Susini S, Aglave M, Alfaro A, Mohamed-Djalim C, Rouanne M, Halse H, Bigorgne A, Tselikas L, Dalle S, Hartl DM, Baudin E, Guettier C, Vibert E, Rosmorduc O, Robert C, Ferlicot S, Parier B, Albiges L, de Montpreville VT, Besse B, Mercier O, Even C, Breuskin I, Classe M, Radulescu C, Lebret T, Pautier P, Gouy S, Scoazec JY, Zitvogel L, Marabelle A, and Bonvalet M
- Subjects
- Humans, T-Lymphocyte Subsets, Receptors, Antigen, T-Cell, CD8-Positive T-Lymphocytes, Neoplasms genetics, Neoplasms metabolism
- Abstract
Background: In addition to anti-PD(L)1, anti-CTLA-4 and anti-LAG-3, novel immune checkpoint proteins (ICP)-targeted antibodies have recently failed to demonstrate significant efficacy in clinical trials. In these trials, patients were enrolled without screening for drug target expression. Although these novel ICP-targeted antibodies were expected to stimulate anti-tumor CD8 + T-cells, the rationale for their target expression in human tumors relied on pre-clinical IHC stainings and transcriptomic data, which are poorly sensitive and specific techniques for assessing membrane protein expression on immune cell subsets. Our aim was to describe ICP expression on intratumoral T-cells from primary solid tumors to better design upcoming neoadjuvant cancer immunotherapy trials., Methods: We prospectively performed multiparameter flow cytometry and single-cell RNA sequencing (scRNA-Seq) paired with TCR sequencing on freshly resected human primary tumors of various histological types to precisely determine ICP expression levels within T-cell subsets., Results: Within a given tumor type, we found high inter-individual variability for tumor infiltrating CD45 + cells and for T-cells subsets. The proportions of CD8
+ T-cells (~ 40%), CD4+ FoxP3- T-cells (~ 40%) and CD4+ FoxP3+ T-cells (~ 10%) were consistent across patients and indications. Intriguingly, both stimulatory (CD25, CD28, 4-1BB, ICOS, OX40) and inhibitory (PD-1, CTLA-4, PD-L1, CD39 and TIGIT) checkpoint proteins were predominantly co-expressed by intratumoral CD4+ FoxP3+ T-cells. ScRNA-Seq paired with TCR sequencing revealed that T-cells with high clonality and high ICP expressions comprised over 80% of FoxP3+ cells among CD4+ T-cells. Unsupervised clustering of flow cytometry and scRNAseq data identified subsets of CD8+ T-cells and of CD4+ FoxP3- T-cells expressing certain checkpoints, though these expressions were generally lower than in CD4+ FoxP3+ T-cell subsets, both in terms of proportions among total T-cells and ICP expression levels., Conclusions: Tumor histology alone does not reveal the complete picture of the tumor immune contexture. In clinical trials, assumptions regarding target expression should rely on more sensitive and specific techniques than conventional IHC or transcriptomics. Flow cytometry and scRNAseq accurately characterize ICP expression within immune cell subsets. Much like in hematology, flow cytometry can better describe the immune contexture of solid tumors, offering the opportunity to guide patient treatment according to drug target expression rather than tumor histological type., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
188. Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.
- Author
-
Campedel L, Compérat E, Cancel-Tassin G, Varinot J, Pfister C, Delcourt C, Gobet F, Roumiguié M, Patard PM, Daniel G, Bigot P, Carrouget J, Eymerit C, Larré S, Léon P, Durlach A, Ruffion A, de Mazancourt ES, Decaussin-Petrucci M, Bessède T, Lebacle C, Ferlicot S, Robert G, Vuong NS, Philip M, Crouzet S, Matillon X, Mège-Lechevallier F, Lang H, Mouracade P, Lindner V, Gougis P, Cussenot O, Rouprêt M, and Seisen T
- Abstract
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 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS)., Results: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%])., Conclusions: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU., (© 2023 BJU International.)
- Published
- 2023
- Full Text
- View/download PDF
189. C3 Glomerulopathy With Concurrent Thrombotic Microangiopathy: Clinical and Immunological Features.
- Author
-
Chabannes M, Rabant M, El Sissy C, Dragon-Durey MA, Vieira Martins P, Meuleman MS, Karras A, Buob D, Bridoux F, Daugas E, Audard V, Caillard S, Olagne J, Kandel C, Ferlicot S, Philipponnet C, Crepin T, Thervet E, Ducloux D, Frémeaux-Bacchi V, and Chauvet S
- Subjects
- Humans, Female, Child, Adolescent, Young Adult, Adult, Middle Aged, Aged, Male, Retrospective Studies, Kidney, Atypical Hemolytic Uremic Syndrome drug therapy, Thrombotic Microangiopathies therapy, Thrombotic Microangiopathies complications, Paraproteinemias complications
- Abstract
Rationale & Objective: C3 glomerulopathy (C3GN) and atypical hemolytic uremic syndrome (aHUS) are 2 distinct rare kidney diseases caused by dysregulation of the alternative complement pathway. Patients with C3GN and concurrent kidney lesions of thrombotic microangiopathy (TMA) have been rarely reported. We characterized the clinical features and underlying immunological abnormalities in these patients., Study Design: Case series., Setting & Participants: Patients with C3GN and concomitant TMA lesions on biopsy registered from 2009 to 2019 in the French National Registry of C3GN., Findings: Among 278 registered patients with C3GN, 16 (6%) had biopsy-proven glomerular and/or vascular TMA lesions. Their median age at diagnosis was 39 years (range, 7-76), and 59% were female. Fourteen of the 16 patients (88%) had an estimated glomerular filtration rate of<30mL/min/1.73m
2 and 3 of 16 (19%) required dialysis. Twelve of the 14 evaluated patients (86%) showed evidence of mechanical hemolysis. Fifty percent of the patients had low C3 levels. Six of the 14 evaluated patients had a rare variant in complement genes, and 4 of the 16 patients (25%) had monoclonal gammopathy. Among the 16 patients, 10 (63%) received eculizumab, 5 (31%) received immunosuppressive therapy, and 4 (25%) received clone-targeted chemotherapy. Median kidney survival was 49 months., Limitations: Small retrospective case series with a limited number of biopsies including electron microscopy., Conclusions: Concomitant C3GN and TMA is extremely rare and is associated with poor kidney outcomes. Genetic or acquired abnormalities of the alternative complement pathway are common as is the presence of monoclonal gammopathy, which may inform the selection of treatment approaches., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
190. Pathological spectrum of hereditary transthyretin renal amyloidosis and clinicopathologic correlation: a French observational study.
- Author
-
Dang J, Ferlicot S, Misrahi M, Mussini C, Kounis I, Rémy P, Samuel D, Planté-Bordeneuve V, Adams D, Funalot B, Snanoudj R, Damy T, Moktefi A, Audard V, and Zaidan M
- Subjects
- Humans, Retrospective Studies, Prealbumin genetics, Plaque, Amyloid pathology, Kidney, Proteinuria pathology, Amyloid Neuropathies, Familial pathology, Kidney Diseases pathology, Immunoglobulin Light-chain Amyloidosis
- Abstract
Background: Cardiac and neurological involvements are the main clinical features of hereditary transthyretin (ATTRv) amyloidosis. Few data are available about ATTRv amyloid nephropathy (ATTRvN)., Methods: We retrospectively included 30 patients with biopsy-proven ATTRvN [V30M (26/30) including two domino liver recipients, S77Y (2/30), V122I (1/30) and S50R (1/30) variants] from two French reference centers. We described the pathological features by comparing amyloid deposits distribution to patients with AL or AA amyloidosis, and sought to determine clinicopathological correlation with known disease-modifying factors such as TTR variant, gender and age at diagnosis., Results: In comparison with AL and AA amyloidosis, ATTRv patients had similar glomerular, arteriolar and arterial amyloid deposits, but more cortical and medullary tubulointerstitial (33%, 44%, 77%, P = .03) involvement. While the presence of glomerular deposits is associated with the range of proteinuria, some patients with abundant glomerular ATTRv amyloidosis had no significant proteinuria. V30M patients had more glomerular (100% and 25%, odds ratio = 114, 95% confidence interval 3.85-3395.00, P = .001) deposits, and higher estimated glomerular filtration rate [50 (interquartile range 44-82) and 27 (interquartile range 6-31) mL/min/1.73 m², P = .004] than non-V30M patients. We did not find difference in amyloid deposition according to gender or age at diagnosis., Conclusion: ATTRvN affects all kidney compartments, but compared with AL/AA amyloidosis, ATTRvN seems to involve more frequently tubulointerstitial areas. V30M patients represents the dominant face of the disease with a higher risk of glomerular/arteriolar involvement. ATTRvN should thus be considered in patients, and potential relatives, with ATTRv amyloidosis and kidney dysfunction, regardless of proteinuria level., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)
- Published
- 2023
- Full Text
- View/download PDF
191. Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease.
- Author
-
Chaba A, Devresse A, Audard V, Boffa JJ, Karras A, Cartery C, Deltombe C, Chemouny J, Contamin C, Courivaud C, Duquennoy S, Garcia H, Joly D, Goumri N, Hanouna G, Halimi JM, Plaisier E, Hamidou M, Landron C, Launay D, Lebas C, Legendre M, Masseau A, Mathian A, Mercadal L, Morel N, Mutinelli-Szymanski P, Palat S, Pennaforte JL, Peraldi MN, Pozdzik A, Schleinitz N, Thaunat O, Titeca-Beauport D, Mussini C, Touati S, Prinz E, Faller AL, Richter S, Vilaine E, Ferlicot S, Von-Kotze C, Belliere J, Olagne J, Mesbah R, Snanoudj R, Nouvier M, Ebbo M, and Zaidan M
- Subjects
- Adult, Middle Aged, Humans, Male, Aged, Female, Rituximab adverse effects, Cohort Studies, Prognosis, Kidney pathology, Immunoglobulin G, Recurrence, Retrospective Studies, Immunoglobulin G4-Related Disease complications, Immunoglobulin G4-Related Disease diagnosis, Immunoglobulin G4-Related Disease drug therapy, Nephritis, Interstitial pathology
- Abstract
Background: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined., Methods: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse., Results: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD., Conclusions: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease., (Copyright © 2023 by the American Society of Nephrology.)
- Published
- 2023
- Full Text
- View/download PDF
192. Renal involvement of lymphomas proven by kidney biopsy: report of 10 cases from a tertiary care center and comparison with the literature.
- Author
-
Urbain F, Ferlicot S, Rocher L, Besson FL, Gomez L, Michot JM, Lazure T, Mariette X, Nocturne G, Lambotte O, Zaidan M, and Noel N
- Subjects
- Humans, Tertiary Care Centers, Kidney pathology, Biopsy, Lymphoma, B-Cell, Marginal Zone pathology, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Lymphomas localized in the kidney are a rare entity that may be challenging to diagnose. We analyzed data from 10 patients with renal involvement of lymphoma diagnosed between 2009 and 2019 on fine needle biopsy from our tertiary center, and compared these with findings of 160 cases reported in the literature. Diffuse large B-cell lymphoma was the main histology subtype (40 and 38% in our sample and in the literature, respectively), followed by low-grade B-cell lymphomas, mostly from the marginal zone (MZ). Altogether, 106 patients had urological inaugural symptoms and 64 had general symptoms. Patients with urological presentation more often had renal masses than diffuse infiltration (p < 0.001), unilateral tumors (p = 0.0036) and low-grade B-cell lymphomas (17 vs 6%, p = 0.043). In both groups, nearly one-fourth of patients had diffuse (stage IV) lymphomas. Overall survival did not differ by the presence of urological/systemic symptoms, stage or aggressive lymphoma status. Notably, 3 of 10 patients from our series had MZ lymphomas associated with primary Sjögren syndrome revealed by acute kidney injury, including one where the autoimmune disease was detected. Lymphoproliferative disorders localized in the kidney are a challenging condition that can lead to detection of aggressive or diffuse lymphomas., (© 2022. Japanese Society of Hematology.)
- Published
- 2022
- Full Text
- View/download PDF
193. Editor's Note: ITPR1 Protects Renal Cancer Cells against Natural Killer Cells by Inducing Autophagy.
- Author
-
Messai Y, Noman MZ, Hasmim M, Janji B, Tittarelli A, Boutet M, Baud V, Viry E, Billot K, Nanbakhsh A, Ben Safta T, Richon C, Ferlicot S, Donnadieu E, Couve S, Gardie B, Orlanducci F, Albiges L, Thiery J, Olive D, Escudier B, and Chouaib S
- Published
- 2022
- Full Text
- View/download PDF
194. Clear cell and papillary renal cell carcinomas in hereditary papillary renal cell carcinoma (HPRCC) syndrome: a case report.
- Author
-
Ferlicot S, Just PA, Compérat E, Rouleau E, Tissier F, Vaessen C, and Richard S
- Subjects
- Biomarkers, Tumor analysis, Carcinoma, Renal Cell chemistry, Carcinoma, Renal Cell secondary, Carcinoma, Renal Cell therapy, DNA Mutational Analysis, Genetic Predisposition to Disease, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Kidney Neoplasms chemistry, Kidney Neoplasms pathology, Kidney Neoplasms therapy, Male, Middle Aged, Neoplastic Syndromes, Hereditary metabolism, Neoplastic Syndromes, Hereditary pathology, Neoplastic Syndromes, Hereditary therapy, Phenotype, Biomarkers, Tumor genetics, Carcinoma, Renal Cell genetics, Germ-Line Mutation, Kidney Neoplasms genetics, Neoplastic Syndromes, Hereditary genetics, Proto-Oncogene Proteins c-met genetics, Von Hippel-Lindau Tumor Suppressor Protein genetics
- Abstract
Background: Hereditary papillary renal cell carcinoma (HPRCC) is a rare autosomal dominant disease characterized by the development of multiple and bilateral papillary type I renal cell carcinomas (RCC) and papillary adenomas caused by activating mutations in the MET proto-oncogene. Classically, distinctive histological features of RCC are described according to the familial renal cell carcinoma syndrome. To date, no clear cell RCC has been reported in HPRCC syndrome., Case Presentation: We describe the case of a 51-year-old man with a germline MET mutation detected on peripheral blood testing, and no germline VHL mutation, who developed numerous papillary tumors but also unexpectedly clear cell renal cell carcinomas. During the follow-up, an adrenal metastasis was observed 7 years after the initial diagnosis corresponding to a clear cell RCC metastasis. By immunohistochemistry, clear cell tumors showed focal cytokeratin 7, moderate racemase, and diffuse and membranous CAIX expression, while papillary tumors expressed strong diffuse cytokeratin 7 and racemase without CAIX positivity. Using FISH, VHL deletion was observed in one of the clear cell tumors, and the metastatic clear cell tumor presented a trisomy of chromosomes 7 and 17. These last genomic alterations are usually detected in papillary RCC, highlighting the potential link between both histological subtypes of tumors and the HPRCC syndrome., Conclusions: The pathologist must be aware that the presence of a non-papillary RCC associated with numerous papillary tumors should not exclude the diagnostic suspicion of HPRCC and thus to perform a thorough genomic study., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
195. Azoospermia and reciprocal translocations: should whole-exome sequencing be recommended?
- Author
-
Ghieh F, Barbotin AL, Prasivoravong J, Ferlicot S, Mandon-Pepin B, Fortemps J, Garchon HJ, Serazin V, Leroy C, Marcelli F, and Vialard F
- Abstract
Background: Although chromosome rearrangements are responsible for spermatogenesis failure, their impact depends greatly on the chromosomes involved. At present, karyotyping and Y chromosome microdeletion screening are the first-line genetic tests for patients with non-obstructive azoospermia. Although it is generally acknowledged that X or Y chromosome rearrangements lead to meiotic arrest and thus rule out any chance of sperm retrieval after a testicular biopsy, we currently lack markers for the likelihood of testicular sperm extraction (TESE) in patients with other chromosome rearrangements., Results: We investigated the use of a single nucleotide polymorphism comparative genome hybridization array (SNP-CGH) and whole-exome sequencing (WES) for two patients with non-obstructive azoospermia and testicular meiotic arrest, a reciprocal translocation: t(X;21) and t(20;22), and an unsuccessful TESE. No additional gene defects were identified for the t(X;21) carrier - suggesting that t(X;21) alone damages spermatogenesis. In contrast, the highly consanguineous t(20;22) carrier had two deleterious homozygous variants in the TMPRSS9 gene; these might have contributed to testicular meiotic arrest. Genetic defect was confirmed with Sanger sequencing and immunohistochemical assessments on testicular tissue sections., Conclusions: Firstly, TMPRSS9 gene defects might impact spermatogenesis. Secondly, as a function of the chromosome breakpoints for azoospermic patients with chromosome rearrangements, provision of the best possible genetic counselling means that genetic testing should not be limited to karyotyping. Given the risks associated with TESE, it is essential to perform WES - especially for consanguineous patients., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
196. Germline mutation in the NBR1 gene involved in autophagy detected in a family with renal tumors.
- Author
-
Adolphe F, Ferlicot S, Verkarre V, Posseme K, Couvé S, Garnier P, Droin N, Deloger M, Job B, Giraud S, Paillerets BB, Gardie B, Richard S, Renaud F, and Gad S
- Subjects
- Adult, Aged, Carcinoma, Renal Cell genetics, Female, Follow-Up Studies, Humans, Kidney Neoplasms genetics, Male, Middle Aged, Pedigree, Prognosis, Autophagy, Carcinoma, Renal Cell pathology, Genetic Predisposition to Disease, Germ-Line Mutation, Intracellular Signaling Peptides and Proteins genetics, Kidney Neoplasms pathology
- Abstract
Hereditary Renal Cell Carcinomas (RCC) are caused by mutations in predisposing genes, the major ones including VHL, FLCN, FH and MET. However, many families with inherited RCC have no germline mutation in these genes. Using Whole Exome Sequencing on germline DNA from a family presenting three different histological renal tumors (an angiomyolipoma, a clear-cell RCC and an oncocytic papillary RCC), we identified a frameshift mutation in the Neighbor of BRCA1 gene 1 (NBR1), segregating with the tumors. NBR1 encodes a cargo receptor protein involved in autophagy. Genetic and functional analyses suggested a pathogenic impact of the mutation. Indeed, functional study performed in renal cell lines showed that the mutation alters NBR1 interactions with some of its partners (such as p62/SQSTM1), leading to a dominant negative effect. This results in an altered autophagic process and an increased proliferative capacity in renal cell lines. Our study suggests that NBR1 may be a new predisposing gene for RCC, however its characterization needs to be further investigated in order to confirm its role in renal carcinogenesis., Competing Interests: Declarations of Competing Interest none, (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
- Full Text
- View/download PDF
197. Transplantation Outcome in Recipients Engrafted With Organs Recovered From the First French Deceased Donor With a SARS-COV-2 Vaccine-induced Thrombotic Thrombocytopenia.
- Author
-
Jamme M, Elalamy I, d'Izarny Gargas T, Pettenati C, Desire E, Tissot A, Rabant M, Lefebvre M, Soorojebally Y, Vourc'h M, Conti F, Ferlicot S, Delahousse M, Sartorius-Brodin A, and Hertig A
- Subjects
- Aged, COVID-19 immunology, COVID-19 virology, COVID-19 Vaccines administration & dosage, ChAdOx1 nCoV-19, Donor Selection, Fatal Outcome, Female, Humans, Male, Middle Aged, Risk Assessment, Risk Factors, Treatment Outcome, Vaccination adverse effects, COVID-19 prevention & control, COVID-19 Vaccines adverse effects, Organ Transplantation adverse effects, Purpura, Thrombotic Thrombocytopenic etiology, SARS-CoV-2 immunology, Tissue Donors
- Abstract
Competing Interests: The authors declare no funding or conflicts of interest.
- Published
- 2021
- Full Text
- View/download PDF
198. Organ Transplantation in Hereditary Fibrinogen A α-Chain Amyloidosis: A Case Series of French Patients.
- Author
-
Meyer L, Ulrich M, Ducloux D, Garrigue V, Vigneau C, Nochy D, Bobrie G, Ferlicot S, Colombat M, Boffa JJ, Clabault K, Mansour J, Mousson C, Azar R, Bacri JL, Dürrbach A, Duvic C, El Karoui K, Hoffmann M, Lionet A, Panescu V, Plaisier E, Ratsimbazafy A, Guerrot D, Vrigneaud L, Valleix S, and François H
- Subjects
- Adolescent, Adult, Aged, Amyloidosis, Familial genetics, Amyloidosis, Familial pathology, Child, Combined Modality Therapy, Disease Progression, Female, Follow-Up Studies, Frameshift Mutation, France epidemiology, Genetic Association Studies, Humans, Kidney pathology, Kidney Failure, Chronic epidemiology, Kidney Failure, Chronic etiology, Kidney Failure, Chronic surgery, Kidney Failure, Chronic therapy, Male, Middle Aged, Mutation, Missense, Point Mutation, Renal Dialysis, Treatment Outcome, Young Adult, Amyloidosis, Familial surgery, Fibrinogen genetics, Kidney Transplantation statistics & numerical data, Liver Transplantation statistics & numerical data
- Abstract
Rationale & Objective: Fibrinogen A α-chain amyloidosis (AFib amyloidosis) is a form of amyloidosis resulting from mutations in the fibrinogen A α-chain gene (FGA), causing progressive kidney disease leading to kidney failure. Treatment may include kidney transplantation (KT) or liver-kidney transplantation (LKT), but it is not clear what factors should guide this decision. The aim of this study was to characterize the natural history and long-term outcomes of this disease, with and without organ transplantation, among patients with AFib amyloidosis and various FGA variants., Study Design: Case series., Setting & Participants: 32 patients with AFib amyloidosis diagnosed by genetic testing in France between 1983 and 2014, with a median follow-up of 93 (range, 4-192) months, were included., Results: Median age at diagnosis was 51.5 (range, 12-77) years. Clinical presentation consisted of proteinuria (93%), hypertension (83%), and kidney failure (68%). Manifestations of kidney disease appeared on average at age 57 (range, 36-77) years in patients with the E526V variant, at age 45 (range, 12-59) years in those with the R554L variant (P<0.001), and at age 24.5 (range, 12-31) years in those with frameshift variants (P<0.001). KT was performed in 15 patients and LKT was performed in 4. In KT patients with the E526V variant, recurrence of AFib amyloidosis in the kidney graft was less common than with a non-E526V (R554L or frameshift) variant (22% vs 83%; P=0.03) and led to graft loss less frequently (33% vs 100%). Amyloid recurrence was not observed in patients after LKT., Limitations: Analyses were based on clinically available historical data. Small number of patients with non-E526V and frameshift variants., Conclusions: Our study suggests phenotypic variability in the natural history of AFib amyloidosis, depending on the FGA mutation type. KT appears to be a viable option for patients with the most common E526V variant, whereas LKT may be a preferred option for patients with frameshift variants., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
199. Indirect effects of severe acute respiratory syndrome coronavirus 2 on the kidney in coronavirus disease patients.
- Author
-
Couturier A, Ferlicot S, Chevalier K, Guillet M, Essig M, Jauréguiberry S, Collarino R, Dargelos M, Michaut A, Geri G, Roque-Afonso AM, Zaidan M, and Massy ZA
- Abstract
Among patients hospitalized for novel coronavirus disease (COVID-19), between 10 and 14% develop an acute kidney injury and around half display marked proteinuria and haematuria. Post-mortem analyses of COVID-19 kidney tissue suggest that renal tubular cells and podocytes are affected. Here we report two cases of collapsing glomerulopathy and tubulointerstitial lesions in living COVID-19 patients. Despite our use of sensitive reverse transcription polymerase chain reaction techniques in this study, we failed to detect the virus in blood, urine and kidney tissues. Our observations suggest that these kidney lesions are probably not due to direct infection of the kidney by severe acute respiratory syndrome coronavirus 2., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)
- Published
- 2020
- Full Text
- View/download PDF
200. [Hereditary kidney cancers: The pathologist's view in 2020].
- Author
-
Verkarre V, Morini A, Denize T, Ferlicot S, and Richard S
- Subjects
- Angiomyolipoma diagnosis, Angiomyolipoma genetics, Angiomyolipoma pathology, Biomarkers, Tumor genetics, Carcinoma, Renal Cell diagnosis, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell pathology, Fumarate Hydratase genetics, Genetic Predisposition to Disease, Genetic Testing, Germ-Line Mutation, Humans, Immunohistochemistry, Kidney Neoplasms diagnosis, Kidney Neoplasms genetics, Neoplastic Syndromes, Hereditary diagnosis, Kidney Neoplasms pathology, Neoplastic Syndromes, Hereditary pathology
- Abstract
Hereditary predispositions to adult kidney tumors involve around 5% of tumors and include a dozen of autosomal dominant syndromes. The most frequent tumors encountered in these setting are clear cell renal cell carcinomas, papillary renal cell carcinomas, chromophobe renal cell carcinomas and angiomyolipomas. Their detection is essential in order to adapt individual care and perform genetic screening of at-risk relatives, especially in the national french network PREDIR, labeled by the National Cancer Institute and dedicated to hereditary predispositions to kidney tumors. Targeted genetic analysis, which was guided in particular by the renal tumor subtype, has recently evolved into genetic analysis using panels of genes. Pathologist contribution's remains however central in the diagnosis of hereditary forms since we currently have immunohistochemical biomarkers that allow us to diagnose two specifically hereditary entities: hereditary leiomyomatosis and renal cell carcinoma associated-renal cell carcinoma, associated with a loss of fumarate hydratase and succinate dehydrogenase-deficient renal cell carcinoma associated with a loss of succinate deshydrogenase B expression. These diagnoses must however be confirmed by the identification of pathogenic germline variation in the corresponding genes. Improvement of kidney tumors characterization has also lead to identify new subtypes, expanding the algorithm of renal tumors associated with hereditary setting. Here we aim to review all subtypes of adult renal tumors encountered in predisposition syndromes., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.