Magali Svrcek

Magali Svrcek
Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien) · Anatomie et Cytologie pathologiques

M.D, PhD

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343
Publications
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Publications

Publications (343)
Article
Background and aims Achieving deep remission, encompassing clinical, endoscopic, and biological remission, is the goal in managing Crohn’s disease (CD). The role of histological remission remains unclear. This study aimed to examine the impact of histological inflammation on clinical relapse risk in CD and explore the relationship between histology...
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Constitutional mismatch repair deficiency (CMMRD), first described 25 years ago, confers an extremely high and lifelong cancer risk, including haematologic, brain, and gastrointestinal tract malignancies, and is associated with several non-neoplastic features. Our understanding of this condition has improved and novel assays to assist CMMRD diagnos...
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Background Microsatellite instability (MSI) due to mismatch repair deficiency (dMMR) is common in colorectal cancer (CRC). These cancers are associated with somatic coding events, but the noncoding pathophysiological impact of this genomic instability is yet poorly understood. Here, we perform an analysis of coding and noncoding MSI events at the d...
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Crée en 2010, avec le soutien de l’Institut national du cancer et de la direction générale de l’offre de soins, le Réseau national de prise en charge des tumeurs rares du péritoine (RENAPE) s’est progressivement structuré et densifié et a permis d’optimiser les filières de soins impliquées dans le traitement des cancers rares du péritoine. Au sein...
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Background: Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear. Methods: A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed. Results: A total of 188 tumour samples...
Article
The term “juvenile-like (inflammatory/hyperplastic) mucosal polyps” (JLIHMP) has been recently introduced to describe a spectrum of polypoid lesions in patients with neurofibromatosis type 1 (NF-1). Due to the scarce number of reported cases and histopathological similarities with entities such as sporadic/syndromic juvenile polyps or inflammatory...
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Background Ovarian pseudomyxoma peritonei (OPMP) are rare, without well-defined therapeutic guidelines. We aimed to evaluate cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat OPMP. Methods Patients from the French National Network for Rare Peritoneal Tumors (RENAPE) database with proven OPMP treated by CRS/...
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Fifteen ovarian pseudomyxoma peritonei (OPMP) without any histological appendiceal mucinous neoplasia or extra-ovarian primary tumors after clinical investigations showed that complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as the primary therapeutic strategy in OPMP led to favorable long-term outcomes (https://doi.org/...
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Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy...
Article
Background Deep remission has become the target in the management of Crohn’s disease (CD). The role of histology in the management of CD has not yet been established. The aim of this work was to study the impact of histological inflammation on the risk of clinical relapse in patients with CD in clinical and endoscopic remission and to study the cor...
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Mismatch Repair Deficiency (dMMR)/Microsatellite Instability (MSI) is a key biomarker in colorectal cancer (CRC). Universal screening of CRC patients for MSI status is now recommended, but contributes to increased workload for pathologists and delayed therapeutic decisions. Deep learning has the potential to ease dMMR/MSI testing and accelerate onc...
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The management of anal squamous cell carcinoma (ASCC) has yet to experience the transformative impact of precision medicine. Conducting genomic analyses may uncover novel prognostic biomarkers and offer potential directions for the development of targeted therapies. To that end, we assessed the prognostic and theragnostic implications of pathogenic...
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Histological assessment of endoscopic biopsies in inflammatory bowel disease [IBD] plays an important role in clinical management, investigative studies, and clinical trials. Scoring schemes consisting of multiple histological items and offering considerable precision are widely available. However, definitions of histological abnormalities are ofte...
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Two tumor (Classical/Basal) and stroma (Inactive/active) subtypes of Pancreatic adenocarcinoma (PDAC) with prognostic and theragnostic implications have been described. These molecular subtypes were defined by RNAseq, a costly technique sensitive to sample quality and cellularity, not used in routine practice. To allow rapid PDAC molecular subtypin...
Article
Background: Mismatch repair deficient (dMMR) tumors displaying microsatellite instability (MSI) represent a paradigm for the success of immune checkpoint inhibitor (ICI)-based immunotherapy, particularly in patients with metastatic colorectal cancer (mCRC). However, a proportion of patients with dMMR/MSI mCRC exhibit resistance to ICI. Identificat...
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LINKED CONTENT This article is linked to Wolf et al papers. To view these articles, visit https://doi.org/10.1111/apt.17495 and https://doi.org/10.1111/apt.17528
Article
Background: Microsatellite instability (MSI) is a negative predictive factor for neoadjuvant chemotherapy in resectable oesogastric adenocarcinoma and a crucial determinant for immunotherapy. We aimed to evaluate reliability of dMMR/MSI status screening performed on preoperative endoscopic biopsies. Methods: Paired pathological samples from biop...
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Background: We pooled data from 2 cohorts of immune checkpoint inhibitors-treated microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer patients to evaluate the prognostic value of RAS/BRAFV600E mutations and Lynch syndrome (LS). Patients and methods: Patients were defined as LS-linked if germline muta...
Article
The two main forms of inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn's disease (CD). Both diseases have inflammatory flare-ups that alternate with periods of remission. The pathologist may examine biopsies of the digestive tract from IBD patients in different contexts: at the time of the initial diagnosis, in the event of a...
Article
Pan-Trk immunohistochemistry (IHC) has been described as a screening test for detection of NTRK fusions in a broad spectrum of tumor types. However, pan-Trk testing in the clinical setting may be limited by many factors, including analytical parameters such as clones, platforms and protocols used. This study aimed to harmonize pan-Trk testing using...
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Background and Aims While post‐inflammatory polyps (PIPs) have historically been a risk factor for colorectal neoplasia (CRN), histologic activity may explain this association. We aimed to assess the impact of histologic activity on CRN occurrence in IBD patients with colonic PIPs. Methods Patients with PIPs on surveillance colonoscopy at Saint‐An...
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Background: Trop-2 is overexpressed in tumor cells of various cancers, including pancreatic ductal adenocarcinoma (PDAC), and has emerged as a potent therapeutic target. We evaluated Trop-2 expression both at the transcriptomic and protein levels, and its correlation with tumor features and patients' outcomes in a large cohort of PDAC. Methods:...
Article
Compared to the general population, patients with inflammatory bowel disease (IBD), both ulcerative colitis (UC) or Crohn's disease (CD), are at increased risk of developing some cancers, particularly colorectal cancers (CRC). CRCs, the vast majority of which are adenocarcinomas, develop from a precancerous lesion called dysplasia (or intraepitheli...
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171 Background: ICI have demonstrated efficacy in patients (pts) with MSI/dMMR mCRC . Lynch (LS) vs sporadic (Sp) status, BRAF V600E and RAS mutations (mt) are known factors of clinical and molecular heterogeneity in this population. We aimed to evaluate the prognostic value of these parameters in ICI-treated MSI mCRC pts. Methods: Pts are drawn fr...
Preprint
Full-text available
Objective: Mismatch Repair Deficiency (dMMR) / Microsatellite Instability (MSI) is a key biomarker in colorectal cancer (CRC). Universal screening of CRC patients for dMMR/MSI status is now recommended, but contributes to increased workload for pathologists and delayed therapeutic decisions. Deep learning has the potential to ease dMMR/MSI testing...
Article
Microsatellite unstable (MSI) colorectal cancers (CRCs) are due to DNA mismatch repair (MMR) deficiency and occurs in15% of non-metastatic diseases and 5% in the metastatic setting. Nearly 30% of MSI CRCs occur in a context of constitutional mutation of the MMR system (Lynch syndrome). Others are sporadic cancers linked to a hypermethylation of the...
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Primary cilia (PC) are important signaling hubs, and we here explored their role in colonic pathology. In the colon, PC are mostly present on fibroblasts, and exposure of mice to either chemically induced colitis-associated colon carcinogenesis (CAC) or dextran sodium sulfate (DSS)-induced acute colitis decreases PC numbers. We generated conditiona...
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Background: Although primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC. Methods: All eligible patients with surgically treated, non-metastatic...
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Background: There are reported variations in the intraoperative management of Crohn's disease. The aim of this consensus statement is to develop a standardised protocol for photographic documentation of intraoperative findings and critical procedural steps in ileocolonic Crohn's disease surgery. Methods: Colorectal surgeons with a specialist int...
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Background Pathogenic variants (PV) of CTNNA1 are found in families fulfilling criteria for hereditary diffuse gastric cancer (HDGC) but no risk estimates were available until now. The aim of this study is to evaluate diffuse gastric cancer (DGC) risks for carriers of germline CTNNA1 PV. Methods Data from published CTNNA1 families were updated and...
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Purpose: In patients with resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma, surgery plus perioperative platinum-based chemotherapy is the standard of care. Perioperative chemotherapy remains debatable for gastric/GEJ adenocarcinoma with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H). Patients and methods...
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Résumé On estime qu’environ 5 % des cancers gastriques surviennent dans un contexte de prédisposition génétique. Le type histologique est important, puisque les gènes majeurs de susceptibilité sont associés à un type spécifique. Le risque est limité au cancer diffus sans syndrome de cancer gastrique diffus héréditaire, associé aux variants pathogèn...
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Objective: To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM). Summary background data: Prophylactic Total G...
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Background: Prophylactic total gastrectomy (PTG) remains the only means of preventing gastric cancer for people with genetic mutations predisposing to Hereditary Diffuse Gastric Cancer (HDGC), mainly in the CDH1 gene. The small but growing cohort of people undergoing PTG at a young age are expected to have a life-expectancy close to the general po...
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Background: The use of neoadjuvant chemotherapy (NAC) in patients with mismatch repair (MMR) deficient (dMMR) localized gastric and oeso-gastric junction (OGJ) adenocarcinoma is subject of debate. Histological response assessment might help to better evaluate the impact of dMMR on response to NAC. Methods: Patients with localized gastric/OGJ ade...
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Context: Polymerase epsilon (POLE) gene missense hotspot mutations can generate pathogenic (p) proofreading defects resulting in hypermutated genomic profiles. Aim: Determine the prevalence, genomic consequences and immunotherapy sensitivity of advanced POLE mutated tumors according to mutation site, primary tumor and tumor mutational burden (TMB)....
Article
Introduction: Pancreatic adenocarcinoma (PAC) is highly heterogeneous, resulting in overall ineffectiveness of most anti-tumor treatments. Two tumor subtypes (Classical and Basal) and two stromal subtypes (“active” and “inactive”) have been described. The Basal and the active stroma have worse prognosis. These subtypes could also be predictive of t...
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Heat shock proteins (HSPs) play oncogenic roles in human tumours. We reported a somatic inactivating mutation of HSP110 (HSP110DE9) in mismatch repair-deficient (dMMR) cancers displaying microsatellite instability (MSI) but did not assess its impact. We evaluated the impact of the Hsp110DE9 mutation on tumour development and the chemotherapy respon...
Preprint
Full-text available
Tumors with microsatellite instability (MSI) represent a paradigm for the success of immune checkpoint inhibitor (ICI)-based immunotherapy, particularly in patients with metastatic colorectal cancer (mCRC). To date however, tools for predicting efficacy of these new therapies are lacking. Here we combined high-throughput DNA and RNA sequencing of t...
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Full-text available
Simple Summary Small bowel adenocarcinoma is a rare tumor. Diagnosis is often obtained at an advanced stage and prognosis remains poor. The aim of this review is to report the recent epidemiological and risk factor data related to small bowel adenocarcinoma. New diagnostic tools are also described in this review. Abstract Adenocarcinomas of the sm...
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Missense mutations in the polymerase epsilon (POLE) gene have been reported to generate proofreading defects resulting in an ultramutated genome and to sensitize tumors to checkpoint blockade immunotherapy. However, many POLE-mutated tumors do not respond to such treatment. To better understand the link between POLE mutation variants and response t...
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Main prognostic factors of anal squamous cell carcinoma (ASCC) are tumor size, differentiation, lymph node involvement, and male gender. However, they are insufficient to predict relapses after exclusive radiotherapy (RT) or chemoradiotherapy (CRT). Fusobacterium nucleatum has been associated with poor prognosis in several digestive cancers. In thi...
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Purpose Histological characteristics at the invasive front may reflect tumor aggressiveness; specifically, tumor budding (Bd) is an emerging prognostic biomarker in colon cancer (CC). We explored further the significance of Bd for risk stratification by evaluating survival of stage III CC patients included in the IDEA-France phase III trial. Patie...
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In the era of immune checkpoint inhibitors, understanding the metastatic microenvironment of proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer (CRC) is of paramount importance to both prognostication and the development of more effective novel therapies. In this study, primary and paired metastasis tissue samples were co...
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Pancreatic ductal adenocarcinoma (PDAC) patients are frequently treated by chemotherapy. Even if personalized therapy based on molecular analysis can be performed for some tumors, PDAC regimens selection is still mainly based on patients' performance status and expected efficacy. Therefore, the establishment of molecular predictors of chemotherapeu...
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13 Background: Optimal treatment duration with immune checkpoint inhibitors (ICI) for MSI/dMMR mCRC pts remains to be determined. Different durations are used, usually a fixed duration of 2 years or treatment until progression or toxicity. The GERCOR NIPICOL phase II study evaluated 1 year of therapy with nivolumab plus ipilimumab for MSI/dMMR mCRC...
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244 Background: In pts with resectable gastric adenocarcinoma or OGA, radical surgery is the only curative option and perioperative chemotherapy seems worthless for those with MSI/dMMR tumors. Methods: We conducted phase II study evaluating the efficacy of neo-adjuvant nivolumab and ipilimumab followed by adjuvant nivolumab in pts with resectable M...
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Background Despite unprecedented benefit from immune checkpoint inhibitors (ICIs) in patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) advanced gastrointestinal cancers, a relevant proportion of patients shows primary resistance or short-term disease control. Since malignant effusions represent an immune-suppres...
Article
In inflammatory bowel disease [IBD], mucosal healing is a major therapeutic target and a reliable predictor of clinical course. However, endoscopic mucosal healing is not synonymous with histological healing, and the additional benefits of including histological remission as a target are unclear. In Crohn´s disease [CD], there are few studies highl...
Preprint
Full-text available
Pancreatic ductal adenocarcinoma (PAC) is a highly heterogeneous and plastic tumor with different transcriptomic molecular subtypes that hold great prognostic and theranostic values. We developed PACpAInt, a multistep approach using deep learning models to determine tumor cell type and their molecular phenotype on routine histological preparation a...
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Résumé Les immunothérapies font partie intégrante de l’arsenal thérapeutique dans de nombreux cancers et peuvent désormais être prescrites en première ligne du traitement des cancers colorectaux métastatiques de phénotype MisMatch Repair déficient/MicroSatellite Instable (dMMR/MSI). Les taux de réponse histologique à l’immunothérapie sont peu docum...
Article
The management of colorectal cancer (CRC) highly relies on the TNM staging system. Tumour deposits (TDs), important histoprognostic factors, are detected in approximately 20% of CRCs and associated with poor prognosis. Integration of TDs in the TNM staging remains a subject of lively debate and differs over the successive TNM classifications. Curre...
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Background Ovarian metastases (OM) of pancreatic adenocarcinoma (PA) (OM-PA) can mimic primary ovarian mucinous carcinoma (POMC) on imaging and histology. These metastases are often symptomatic and not highly chemosensitive, so that oophorectomy may be considered. Aims The aims of this study were to compare the characteristics of OM-PA and POMC, a...
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Résumé La prise en charge du cancer colorectal (CCR) repose largement sur la stadification TNM. Afin d’améliorer cette stadification, il est essentiel d’identifier de nouveaux marqueurs histologiques. Parmi ceux-ci, les dépôts tumoraux (DTs) ou « tumor deposits » en anglais, définis comme des foyers tumoraux présents dans la sous-séreuse colique ou...
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Purpose: Our team previously defined six quantitative transcriptomic components, and a classification in five subtypes by association of these components. In this study, we compared the robustness of quantitative components and qualitative classifications from different transcriptomic profiling techniques, investigated their clinical relevance and...
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Introduction Many diseases can imitate inflammatory bowel disease [IBD] clinically and pathologically. This review outlines the differential diagnosis of IBD and discusses morphological pointers and ancillary techniques that assist with the distinction between IBD and its mimics. Methods European Crohn’s and Colitis Organisation [ECCO] Topical Rev...
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Background: In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e., stage III pN1c tumors). We aimed at evaluating the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer. Patients and methods: All participa...
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Intraductal papillary mucinous neoplasms (IPMN) are common and one of the main precursor lesions of pancreatic ductal adenocarcinoma (PDAC). PDAC derived from an IPMN is called intraductal papillary mucinous carcinoma (IPMC) and defines a subgroup of patients with ill-defined specificities. As compared to conventional PDAC, IPMCs have been associat...
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Résumé Introduction Le kyste cilié cutané ou kyste mullérien cutané est un kyste cutané rare, aux profils histologique et immunohistochimique superposables à celui de la trompe de Fallope. Observation Exérèse d’un kyste cutané de la hanche chez une patiente de 19 ans, dont les profil histologique et immunohistochimique font porter le diagnostic d...
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Background A wide variety of intestinal and non-intestinal diseases can resemble chronic idiopathic inflammatory bowel disease (IBD) clinically and/or pathologically. The aim of the current Topical Review was to explore the differential diagnosis of IBD and to discuss clinical, histomorphological features and ancillary techniques that help distingu...
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3580 Background: Immune checkpoint inhibitors (ICI) have demonstrated efficacy in patients (pts) with MSI/dMMR mCRC. We aimed to evaluate clinical, pathological and molecular factors associated with progression-free survival (PFS) and overall survival (OS) in ICI-treated pretreated mCRC patients (pts). Methods: Pts are drawn from a prospective coho...
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4141 Background: Pancreatic adenocarcinoma (PAC) is predicted to be the second cause of death by cancer in 2030 and its prognosis has seen little improvement in the last decades. PAC is a very heterogeneous tumor with preeminent stroma and multiple histological aspects. Omic studies confirmed its molecular heterogeneity, possibly one of the main fa...
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e15537 Background: Inhibitors of tropomyosin receptor kinase (TRK) have shown promising activity against neurotrophic TRK ( NTRK) fusion-driven cancers, regardless of tumor histotype or cell of origin. NTRK gene fusions are observed in less than 1% of colorectal cancers (CRCs). CRCs harboring wild-type BRAF and KRAS and MisMatch Repair deficiency (...
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Background Few patients with pancreatic adenocarcinoma (PAC) are eligible for surgery. Patients with early relapse have a poor prognosis and might be better candidates for a medical approach. Clinical and pathological parameters only partially predict recurrence and are only obtained after surgery. PAC subtypes based on gene expression were propose...