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Conjunctival-pigmented tumors are rare, but they are one of the most commonly encountered by the pathologist working with the department of ophthalmology. Nevus and melanoma can be encountered and have some histological difference compared to their cutaneous counterpart. Primary acquired melanosis (PAM) is a conjunctival specific entity. This clinical term includes several histological lesions ranging from benignity to melanoma precursor lesion. Histologic examination determines the therapy and the risk of progression to melanoma. We present here a histopathological, clinical and therapeutic synthesis of conjunctival-pigmented lesions, emphasizing the importance of a good understanding between clinicians and pathologists.

// Lucile Broncy 1 , Basma Ben Njima 2 , Arnaud Mejean 3 , Christophe Beroud 4, 5 , Khaled Ben Romdhane 2 , Marius Ilie 6 , Veronique Hofman 6 , Jane Muret 7 , Paul Hofman 6 , Habiba Chaabouni Bouhamed 2 , and Patrizia Paterlini-Brechot 1, 8 1 INSERM Unit 1151, Faculte de Medecine Paris Descartes, Paris, France 2 Genetics and Pathology Departments, University of Tunis, Tunis, Tunisia 3 Service d’Urologie, Hopital Europeen Georges Pompidou, Paris, France 4 Aix Marseille University, INSERM, MMG, Marseille, France 5 APHM, Hopital TIMONE Enfants, Laboratoire de Genetique Moleculaire, Marseille, France 6 Laboratoire de pathologie clinique et Biobank BB-0033-00025, Centre Hospitalo-Universitaire de Nice, Nice, France 7 Institut Curie, PSL Research University, Departement d’Anesthesie Reanimation Douleur, Paris, France 8 Laboratoire de Biochimie A, Hopital Necker-Enfants Malades, Paris, France Correspondence to: Patrizia Paterlini-Brechot, email: patrizia.paterlini@inserm.fr Keywords: liquid biopsy; circulating cancer cells; ISET ® (Isolation by Size of Tumour/Trophoblastic Cells) technology; clear cell renal cell carcinoma; VHL mutation Received: October 07, 2017 Accepted: March 24, 2018 Published: April 13, 2018 ABSTRACT Context: Circulating Rare Cells (CRC) are non-haematological cells circulating in blood. They include Circulating Cancer Cells (CCC) and cells with uncertain malignant features (CRC-UMF) according to cytomorphology. Clear cell renal cell carcinomas frequently bear a mutated Von Hippel-Lindau (VHL) gene. Aim: To match blind genetic analysis of CRC and tumor samples with CRC cytopathological diagnosis. Results: 29/30 patients harboured CRC (20 harboured CCC, 29 CRC-UMF) and 25/29 patients carried VHL mutations in their tumour. 205 single CRC (64 CCC, 141 CRC-UMF) provided genetic data. 57/57 CCC and 104/125 CRC-UMF from the 25 patients with VHL-mutated tumor carried the same VHL mutation detected in the tumor. Seven CCC and 16 CRC-UMF did not carry VHL mutations but were found in patients with wild-type VHL tumor tissue. Conclusions: All the CCC and 83,2% (104/125) of the CRC-UMF were found to carry the same VHL mutation identified in the corresponding tumorous tissue, validating cytopathological identification of CCC in patients with clear cell renal cell carcinoma. Methods: The blood of 30 patients with clear cell renal cell carcinoma was treated by ISET ® for CRC isolation, cytopathology and single-cell VHL mutations analysis, performed blindly and compared to VHL mutations of corresponding tumor tissues and leukocytes.

Early detection of cancer, particularly through screening of high-risk patients, is essential to decreasing the mortality due to cancer, notably lung cancer (1). Early detection is made possible by sampling of cytological and/or histological specimens that provide a diagnosis of the precancerous lesion.

Despite the major advances in treatment of lung carcinomas, in particular of advanced or metastatic non-small cell lung carcinomas (NSCLC) with immunotherapies, a high number of patients do not benefit from this effective treatment. These patients either do not express a sufficient level of biomarkers of companion or complementary tests [PD-L1 and tumor mutational burden (TMB)] for anti-PD1/PD-L1 treatments, or, do not respond to immunotherapies and even worse have a rapid progression of their tumor.

International audience; Next-generation sequencing (NGS) may enable more focused and highly personalized cancer treatment, with the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines now recommending NGS for daily clinical practice for several tumor types. However, NGS implementation, and therefore patient access, varies across Europe; a multi-stakeholder collaboration is needed to establish the conditions required to improve this discrepancy. In that regard, we set up European Alliance for Personalised Medicine (EAPM)-led expert panels during the first half of 2021, including key stakeholders from across 10 European countries covering medical, economic, patient, industry, and governmental expertise. We describe the outcomes of these panels in order to define and explore the necessary conditions for NGS implementation into routine clinical care to enable patient access, identify specific challenges in achieving them, and make short- and long-term recommendations. The main challenges identified relate to the demand for NGS tests (governance, clinical standardization, and awareness and education) and supply of tests (equitable reimbursement, infrastructure for conducting and validating tests, and testing access driven by evidence generation). Recommendations made to resolve each of these challenges should aid multi-stakeholder collaboration between national and European initiatives, to complement, support, and mutually reinforce efforts to improve patient care.

BACKGROUND Pembrolizumab monotherapy is a standard-of-care treatment for the first- and second-line treatment of advanced non-small cell lung cancer with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) values ≥ 50% and ≥ 1%, respectively. PD-L1 testing with the PD-L1 immunohistochemistry (IHC) 22C3 pharmDx companion assay has been validated on tumor tissue with the Dako Autostainer Link 48 (ASL48). 22C3 anti-PD-L1 antibody-based laboratory-developed tests (LDTs) compatible with other autostainers and cytology samples are essential to support pembrolizumab treatment decisions across institutions globally. METHODS ASL48 and BenchMark Ultra LDTs were optimized for the evaluation of cytology samples through comparisons with cell lines with known PD-L1 expression levels (strong, moderate, and negative). The PD-L1 TPS was then evaluated for 70 paired biopsy and cytology samples (bronchial washes, n = 40; pleural effusions, n = 30) with these LDTs. Biopsy and cytology LDT TPS values were also compared with a subset of biopsy samples (n = 37) evaluated with the PD-L1 IHC 22C3 pharmDx assay on the ASL48. RESULTS Intraclass correlation coefficients of 0.884 to 0.898 were observed for biopsy samples versus cytology samples with the ASL48 and BenchMark Ultra LDTs. Concordance was high, regardless of the TPS cut point (

Background: Circulating tumor cells (CTCs) hold potential for noninvasive diagnosis, prognosis and prediction testing in non-small cell lung cancer (NSCLC) patients. Minimizing degradation or loss of CTCs is pivotal for detection and profiling of the low abundance and fragile CTCs, particularly in clinical trials. We prospectively investigated (NCT02372448) whether a new blood collection device performed better compared to commonly used K3EDTA tubes, when subjected to long-term sample storage. Methods: Blood samples were drawn into K3EDTA and blood collection tubes (BCT) (Streck), and filtered by the Isolation by SizE of Tumor/Trophoblastic Cells (ISET® system), for CTC detection in two study populations of NSCLC patients; the training set of 14 patients with stage II/IV NSCLC, and the validation set of 36 patients with stage IV NSCLC). MET expression was evaluated by immunocytochemistry (ICC) and anaplastic lymphoma kinase (ALK) gene rearrangement by break-apart fluorescence in situ hybridization (FISH) on ISET-enriched CTCs. Results: Blood processed after 24 h and 48 h in BCT tubes showed stable CTCs counts and integrity, whereas CTCs in K3EDTA tubes showed an altered morphology in all patients. CTCs recovered in BCT or K3EDTA tubes at 24 and 48 h were evaluable by ICC for MET expression and by FISH for ALK rearrangement. Conclusions: The BCT tubes gave a high yield and preserved the integrity of CTCs after 24 and 48 h of storage at room temperature, which facilitate their molecular characterization in NSCLC patients entering clinical trials.

Pathologists have been, are and will be always implicated in the diagnosis of infectious and tropical diseases. The resurgence of opportunistic infections due to the development of immunosuppressive drugs, the increase of migratory involvements draining tropical infections and the last epidemics spotlight the importance of pathologists in the field of infectious diseases. However, cancer is nowadays the first preoccupation of pathologists, which is constantly subject to evaluate diagnostic and prognostic markers and factors predictive to targeted therapy response or immunotherapy. As tumor pathology, infectious diseases require more sophisticated and rapidly changing complementary techniques, appraisals and perhaps a national network of diagnosis. The infectious pathology club committee carries out here a census of methods used in the diagnosis of infectious diseases in France in 2015 and particularly the different techniques used by laboratories to perform infectious diseases diagnosis. This will lay down the foundation of a future national organization of the infectious pathology in providing efficient services (diagnostic support, complementary tools) for the community of French pathologists in this specific domain of competence.

Resume La pratique des biopsies liquides (BL) revolutionne la prise en charge des patients atteints d’un cancer pulmonaire en phase metastatique. De nombreux oncologues utilisent desormais cette approche en pratique quotidienne, selon des indications bien precises, pour la detection des mutations activatrices ou de resistance de l’EGFR. Les tests realises a partir de l’ADN plasmatique ont ete approuves en cas de positivite comme pouvant etre associes aux traitements par inhibiteurs de tyrosine kinase en cas. Le rearrangement d’ALK identifie au niveau des tissus tumoraux est une autre cible d’interet essentiel dans les cancers pulmonaires puisqu’associee a un traitement pouvant etre accessible pour les patients positifs. Par analogie avec l’EGFR, l’utilisation des BL pour detecter les alterations genomiques d’ALK (rearrangements ou mutations) a donc ete rapidement envisagee. Tres prometteuse, cette approche presente alors certaines limites et ne connait pas encore une diffusion aussi importante que les tests sanguins ciblant l’EGFR. Hormis pour ces deux cibles therapeutiques, les BL sont applicables pour l’evaluation du statut genomique d’autres genes d’interet chez un patient atteint d’un cancer pulmonaire (ROS1, RET, NTRK MET, BRAF, HER2, etc.). Cette evaluation peut etre alors recherchee par une approche ciblee ou grâce a des techniques ciblant des panels plus ou moins complexes. Compte tenu de la multiplicite des cibles potentielles pour des essais cliniques, les techniques de sequencage de nouvelle generation appliquees a l’ADN circulant sont en plein essor. Cette revue fait le point sur l’apport des BL dans la prise en charge therapeutique des cancers pulmonaires en phase metastatique, sur les limites actuelles de cette approche et aborde certaines perspectives.

Resume L’immunohistochimie (IHC) PD-L1 est le seul biomarqueur predictif propose en oncologie thoracique dans le cadre de l’immunotherapie PD-L1/PD1. Dans ce contexte, les etudes publiees relatives a ce biomarqueur sont nombreuses, mais elles soulevent des interrogations sur la nature de l’anticorps a utiliser et dans quelle(s) condition(s) ; le seuil de positivite a appliquer ; le message et les informations a etablir avec l’oncologue thoracique ; l’integration de cette activite dans le fonctionnement quotidien d’un laboratoire d’anatomo-cytopathologie. L’IHC PD-L1 a un objectif « theranostic », ce qui implique de rendre un examen fiable, devant eviter imperativement, compte tenu des consequences therapeutiques, un resultat faussement positif ou faussement negatif. Ainsi, l’IHC PD-L1 est un test diagnostic « compagnon » ou « complementaire » selon le clone utilise, la molecule administree au patient et l’indication therapeutique. L’interpretation de l’IHC PD-L1 demande une expertise et une formation specifique des pathologistes. Des recommandations internationales ou nationales devraient rapidement permettre d’avoir une meilleure visibilite sur les bonnes pratiques d’utilisation des differents anticorps anti-PD-L1. Cette revue fait le point sur l’utilisation des differents anticorps PD-L1 en IHC dans le cadre des cancers pulmonaires non a petites cellules (CPNPC) en phase metastatique et discute leur utilisation comme test diagnostic compagnon ou complementaire. Puis sont abordees les limites de l’IHC PD-L1, ainsi que les perspectives a venir afin d’ameliorer le potentiel predictif de ce biomarqueur dans le cadre de l’immunotherapie des CPNPC.

Simple Summary Conjunctival melanoma (CM) is a small but highly aggressive and infiltrative periocular malignancy. Despite wide surgical excision followed by adjuvant therapy, about one third and one quarter of patients will experience local recurrence and metastatic spread, respectively. The management of locally advanced (≥T2) tumours may require mutilating surgeries such as orbital exenteration to achieve local control. The last decade has been marked by the emergence of eye-sparing strategies based on wide surgical excision followed by adjuvant proton beam therapy. More recently, new genetic and immunological insights have incriminated several signalling pathways (MAPK, PI3K-AKT) and immune cells, making CM a “targetable” malignancy. Anti-BRAF and anti-MEK targeted therapies and immunotherapies have revolutionized the current management of CM through the use of new eye-sparing strategies and treatment of metastases. Abstract Although its incidence has increased over the last decades, conjunctival melanoma (CM) remains a rare but challenging periocular malignancy. While there is currently no recognized standard of care, “no-touch” surgical excision followed by adjuvant treatments is usually recommended. Despite its small size, managing CM is challenging for clinicians. The first challenge is the high risk of tumour local recurrence that occurs in about one third of the patients. The management of locally advanced CM (≥T2) or multiple recurrences may require mutilating surgeries such as orbital exenteration (OE). The second challenge is the metastatic spread of CM that occurs in about one quarter of patients, regardless of whether complete surgical excision is performed or not. This highlights the infiltrative and highly aggressive behaviour of CM. Recently, attention has been directed towards the use of eye-sparing strategies to avoid OE. Initially, wide conservative surgeries followed by customized brachytherapy or radiotherapy have appeared as viable strategies. Nowadays, new biological insights into CM have revealed similarities with cutaneous melanoma. These new findings have allowed clinicians to reconsider the management of locally advanced CM with “medical” eye-sparing treatment as well as the management of metastatic spread. The aim of this review was to summarize the current and future perspectives of treatment for CM based on recent biological findings.

SummaryCancer patients are vulnerable to COVID-19 with consequences on treatment delays and on mortality rate. This Comment explores the interaction between COVID-19 and cancer with attention paid to the modulation by cancer treatments of both ADAM17 and TMPRSS2, the proteases which control ACE2 processing, the SARS-CoV-2 target.

// Marius Ilie 1, 2, 3 , Catherine Butori 1, 3 , Sandra Lassalle 1, 2, 3 , Simon Heeke 2 , Nicolas Piton 4 , Jean-Christophe Sabourin 4 , Virginie Tanga 3 , Kevin Washetine 1, 3 , Elodie Long-Mira 1, 2, 3 , Priscilla Maitre 3 , Nathalie Yazbeck 2 , Olivier Bordone 3 , Virginie Lespinet 3 , Sylvie Leroy 5 , Charlotte Cohen 6 , Jerome Mouroux 2, 6 , Charles Hugo Marquette 2, 5 , Veronique Hofman 1, 2, 3 and Paul Hofman 1, 2, 3 1 Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, FHU OncoAge, University Cote d’Azur, Nice, France 2 IRCAN Inserm U1081/CNRS 7284, FHU OncoAge, University Cote d’Azur, Nice, France 3 Hospital-related Biobank (BB-0033-00025), Pasteur Hospital, FHU OncoAge, University Cote d’Azur, Nice, France 4 Department of Pathology, Rouen University Hospital, Rouen, France 5 Department of Pulmonary Medicine and Thoracic Oncology, Pasteur Hospital, FHU OncoAge, University Cote d’Azur, Nice, France 6 Department of Thoracic Surgery, Pasteur Hospital, FHU OncoAge, University Cote d’Azur, Nice, France Correspondence to: Paul Hofman, email: hofman.p@chu-nice.fr Keywords: NSCLC, EGFR, targeted therapy, optimization, PCR Received: March 21, 2017 Accepted: September 19, 2017 Published: October 04, 2017 ABSTRACT Treatment with EGFR inhibitors is limited to patients with advanced/metastatic non-small cell lung cancer who have known EGFR mutations. Currently, patient care has to respond to several imperatives to make these inhibitors broadly available to all patients; fast and accurate detection of EGFR mutations by a sensitive and specific standardized cost-effective method, easy-to-implement in settings with limited expertise in molecular diagnostics. We evaluated the Idylla™ EGFR Mutation Assay (Biocartis) for the detection of EGFR mutations in archived formalin-fixed paraffin-embedded (FFPE) tumor samples from a series of 55 patients with lung adenocarcinoma and compared these results with those obtained by a pyrosequencing ISO-15189 accredited laboratory method. The comparison was made on both whole surgical tumor sections and on three artificially constructed small biopsies (~1 mm) from the same FFPE blocks. Cost-effectiveness and turnaround time comparison between the two methods was performed. On both whole tissue sections and on biopsy cores, the Idylla™ and pyrosequencing had an agreement of 95% (52/55). The Idylla™ EGFR Assay produced results faster and more cost-effective than pyrosequencing. The Idylla™ system showed a good sensitivity and was cost-saving in our setting. Because of the easy workflow, the Idylla™ system has the potential to expand EGFR testing to more pathology laboratories in a reliable and fast manner.

The growing complexity of biobanking requires dedicated professional staff who are trained in multiple aspects of the biobanking process, including technical, managerial, regulatory, and ethical aspects, and who have a good understanding of the challenges of biospecimen research, but also of the challenges related to the sustainability of future biobanks. Up to the present, biobanking staff have been trained in an ad-hoc manner, usually through specific short duration courses, for example, summer schools. In this article, we describe the development/establishment of a systematic 2-year training program at the Master level intended for students with a background in life sciences and providing them with a professional qualification as a "Biobank Manager." This course was developed in 2010 as a joint initiative of the Catholic University of Lyon and the University of Nice-Sophia-Antipolis (France). The multidisciplinary training offers courses on biobank design and infrastructure, on pre- and postanalytical processing of different types of biospecimens, on protocol development, on ethical and regulatory aspects, as well as an introduction to epidemiology and translational research. In parallel, students also receive generic training in management, budget planning, data analysis, and statistics, as well as 11 months of hands-on training in various biobanks handling human, animal, plant, or microbial biospecimens. Four groups of students have graduated since 2012, for a total of 44 students, who all found jobs in biobanking within 6 months of graduation.

MicroRNAs (miRs) participate in tumor growth and dissemination by regulating expression of various target genes. MiR-223-3p is suspected of being involved in head and neck squamous cell carcinoma (HNSCC) growth although its precise role has not been elucidated. In this study, we showed that miR-223-3p is present in biopsies of HNSCC patients and that its presence is correlated with high neutrophil infiltrate. We found that overexpression of miR-223-3p slightly increased proliferation of the CAL27 squamous carcinoma cell line both in vitro and in vivo. Moreover, miR-223-3p induced CAL27 apoptosis in an orthotopic xenograft mouse model, counteracting the proliferative effect and resulting in no impact on overall tumor growth. We analyzed the effect of miR-223-3p overexpression on signaling pathways and showed that it induced pERK2, pAKT and AKT, consistent with an increase in cell proliferation. In addition, we found that miR-223-3p reduced the STAT3 level correlating with increased cell apoptosis and inhibited vasculature formation. In HNSCC tissues, miR-223-3p expression was inversely correlated to CD31, highlighting the relationship between miR-223 and vessel formation. Finally, we studied the effect of miR-223-3p on response to selected anticancer agents and showed that cells expressing miR-223-3p are more resistant to drugs, notably cetuximab. In conclusion, our study is the first to show the antiangiogenic properties of miR-223-3p in HNSCC patients and to question whether expression levels of miR-223-3p can be evaluated as an indicator of eligibility for non-treatment of HNSCC patients with cetuximab.

Background: Assessment of actionable EGFR mutations is mandatory for treatment-naïve advanced or metastatic non-squamous lung carcinoma (NSLC), but the results need to be obtained in less than 10 working days. For rapid EGFR testing, an EGFR-specific polymerase chain reaction (PCR) assay is an alternative and simple approach compared to next generation sequencing (NGS). Here, we describe how a rapid EGFR-specific PCR assay can be implemented in a single laboratory center (LPCE, Nice, France) as reflex testing in treatment-naïve NSLC. Methods: A total of 901 biopsies from NSLC with more than 10% of tumor cells were prospectively and consecutively evaluated for EGFR mutation status between November 2017 and December 2019 using the Idylla system (Biocartis NV, Mechelen, Belgium). NGS was performed for nonsmokers with NSLC wild type for EGFR, ALK, ROS1, and BRAF and with less than 50% PD-L1 positive cells using the Hotspot panel (Thermo Fisher Scientific, Waltham, MA, USA). Results: Results were obtained from 889/901 (97%) biopsies with detection of EGFR mutations in 114/889 (13%) cases using the Idylla system. Among the 562 EGFR wild type tumors identified with Idylla, NGS detected one actionable and one nonactionable EGFR mutation. Conclusions: Rapid and targeted assessment of EGFR mutations in treatment-naïve NSLC can be implemented in routine clinical practice. However, it is mandatory to integrate this approach into a molecular algorithm that allows evaluation of potentially actionable genomic alterations other than EGFR mutations.

T790M mutations inEGFR-mutated non-small cell lung cancer (NSCLC) account for nearly 50% of acquired resistance mechanisms to EGFR-TKIs. Earlier studies suggested that tumor T790M could also be detected in TKI-naïve EGFR-mutated NSCLC. The aim of the study is to assess the prevalence and clinical significance of quantification of tumor pre-treatment T790M subclones.We analyzed 366 EGFR-mutated NSCLC patients of the real-life IFCT Biomarkers France study with available pre-treatment formalin-fixed paraffin-embedded (FFPE) tumor DNA before treatment by first/second-generation EGFR-TKI. We used ultra-sensitive Droplet Digital Polymerase Chain Reaction (ddPCR) QX200 (BIO-RAD®, Hercules, CA, USA). All samples were tested in duplicate.ddPCR identified T790M in 19/240 specimens (8%). T790M-positive and T790M-negative populations were not different for clinical baseline characteristics. T790M Variant Allele Frequency (VAF) was 0.01% 0.1%, 0.1% 1%, 1% 10%, and10% in five (26.3%), six (31.6%), six (31.6%), and two (10.5%) patients, respectively. T790M VAF was0.1% in 11/13 (84%) patients with rapid (3 months) or usual progression (3-20 months) compared to 0/3 with low progression (20 months) (p = 0.02). In a Cox model, T790M mutation positivity was correlated with overall survival (OS) and progression-free survival (PFS) for 10%VAF1% (hazard ratio [HR] = 2.83, 95% confidence interval [CI] 1.13-7.07, p = 0.03; HR=3.62, 95%CI 1.43-4.92, p = 0.007, respectively) and for VAF10% (HR = 19.14, 95%CI 4.35-84.26, p 0.001; HR = 17.89, 95%CI 2.21-144.86, p = 0.007, respectively).Ultra-sensitive detection of tumor T790M mutation concerned 8% of EGFR-mutated TKI-naïve NSCLC patients and has a negative prognostic value only for T790M VAF over 1%.

Since its initial recognition in December 2019, Coronavirus disease 19 (COVID-19) has quickly spread to a pandemic infectious disease. The causative agent has been recognized as a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affecting the respiratory tract. To date, no vaccines are available nor any specific treatment. To limit the number of infections, strict directives have been issued by governments that have been translated into equally rigorous guidelines notably for post-mortem examinations by international and national scientific societies. The recommendations for biosafety control required during specimen collection and handling have strongly limited the practice of autopsies of the COVID-19 patients to a few adequate laboratories. A full pathological examination has always been considered an important tool to better understand the pathophysiology of diseases, especially when the knowledge of an emerging disorder is limited and the impact on the healthcare system is significant. The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies. Ancillary tools such as electron microscopy and molecular biology used on autoptic tissue samples from autopsy are also significantly contributing to confirm and/or identify new aspects useful for a deeper knowledge of the pathogenetic mechanisms. This article will review and summarize the pathological findings described in COVID-19 until now, chiefly focusing on the respiratory tract, highlighting the importance of autopsy towards a better knowledge of this disease.

International audience; Background - The introduction of liquid biopsy using PCR-based assays into routine practice has had a strong impact on the treatment of EGFR-mutated lung adenocarcinoma and is now commonly used for routine testing of EGFR mutations in certain clinical settings. To assess whether the claimed benefits of PCR-based assays hold true in daily practice at a multicenter clinical institution, we assessed how treatment decisions are affected by PCR-based assays for the analysis of EGFR mutations from plasma samples in a centralized laboratory (LPCE, Nice, France). Patients and methods - A total of 345 samples were analyzed using the US Food and Drug Administration-approved Cobas EGFR Mutation Test v2 and 103 using the Therascreen EGFR Plasma RGQ PCR Kit over 3 years (395 samples from 324 patients). Eleven plasma samples were validated independently using Cobas at 3 institutions, and 130 samples were analyzed using Stilla digital PCR. Clinical data were collected for 175 (54%) of 324 patients. Results - Cobas was superior to the Therascreen assay and demonstrated 100% reproducibility. Digital PCR showed only 48%, 83%, and 58% concordance with Cobas for exon 19 deletions, L858R mutations, and T790M mutations, respectively. Liquid biopsies helped inform and change treatment when resistance occurred and enabled the detection of EGFR mutations in patients when biopsy tissue results were unavailable. Conclusion - PCR-based assays are a fast and convenient test, allowing the detection of primary and secondary EGFR mutations from plasma. Cobas proved to be a reliable test, whereas digital PCR produced too many inconclusive results to be currently recommended as a principal testing device.

A questionnaire on biomarker testing previously used in central European countries was extended and distributed in Western and Central European countries to the pathologists participating at the Pulmonary Pathology Society meeting 26-28 June 2019 in Dubrovnik, Croatia. Each country was represented by one responder. For recent biomarkers the availability and reimbursement of diagnoses of molecular alterations in non-small cell lung carcinoma varies widely between different, also western European, countries. Reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. The support for testing from alternative sources, such as the pharmaceutical industry, is no doubt partly compensating for the lack of public health system support, but it is not a viable or long-term solution. Ideally, a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. As biomarker enabled therapies deliver a 50% better probability of outcome success, improved and unbiased reimbursement remains a major challenge for the future. ispartof: TRANSLATIONAL LUNG CANCER RESEARCH vol:9 issue:3 pages:887-897 ispartof: location:China status: published

Summary It has been found that occurrence of immune-related adverse events (irAEs) is associated with outcome in the treatment of advanced non-small-cell lung cancer (NSCLC) with anti-programmed cell death (PD)-1 or anti-PDL1 agents. Independent correlation with survival was not consistently demonstrated and correlation with the number of toxicities was also not previously described. All patients treated with nivolumab for advanced NSCLC, in the second line setting, were retrospectively reviewed in a single-center from March 2015 to March 2017. Sixty-nine patients were identified. After a median follow-up of 13 months (95% CI: 10.8; 15.3), there were 46 tumor progressions and 37 deaths. The 6-month and one-year progression-free survival (PFS) and overall survival (OS) rates were 29%/61% and 24%/49%, respectively. Thirty-one patients (44.9%) presented irAEs. Patients presenting tumor response to previous chemotherapy had a higher rate of irAEs (P = 0.01) and a better OS (HR = 2, P = 0.04). Occurrence of irAEs correlated with OS in multivariate analysis (HR = 0.4, 95% CI [0.19; 0.8], P = 0.02). The number of irAEs correlated with tumor response, PFS and OS in univariate analysis. Having ≥ 2 irAEs correlated with better outcome compared with one irAE, which correlated with better tumor response and PFS in comparison with 0 irAE, in multivariate analysis. In this study, irAEs was associated with a better outcome in patients treated with nivolumab for advanced NSCLC in the second line setting. Interestingly, the number of irAEs correlated with tumor response and PFS.

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms., The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Here, Alcala and colleagues present a multi-omics analysis of these tumours, revealing distinct molecular and prognostic subgroups.

International audience; Lung cancer is the leading cause of cancer death worldwide, with poor prognosis and a high rate of recurrence despite early surgical removal. Hypoxic regions within tumors represent sources of aggressiveness and resistance to therapy. Although long non-coding RNAs (lncRNAs) are increasingly recognized as major gene expression regulators, their regulation and function following hypoxic stress are still largely unexplored. Combining profiling studies on early-stage lung adenocarcinoma (LUAD) biopsies and on A549 LUAD cell lines cultured in normoxic or hypoxic conditions, we identified a subset of lncRNAs that are both correlated with the hypoxic status of tumors and regulated by hypoxia in vitro. We focused on a new transcript, NLUCAT1, which is strongly upregulated by hypoxia in vitro and correlated with hypoxic markers and poor prognosis in LUADs. Full molecular characterization showed that NLUCAT1 is a large nuclear transcript composed of six exons and mainly regulated by NF-κB and NRF2 transcription factors. CRISPR-Cas9-mediated invalidation of NLUCAT1 revealed a decrease in proliferative and invasive properties, an increase in oxidative stress and a higher sensitivity to cisplatin-induced apoptosis. Transcriptome analysis of NLUCAT1-deficient cells showed repressed genes within the antioxidant and/or cisplatin-response networks. We demonstrated that the concomitant knockdown of four of these genes products, GPX2, GLRX, ALDH3A1, and PDK4, significantly increased ROS-dependent caspase activation, thus partially mimicking the consequences of NLUCAT1 inactivation in LUAD cells. Overall, we demonstrate that NLUCAT1 contributes to an aggressive phenotype in early-stage hypoxic tumors, suggesting it may represent a new potential therapeutic target in LUADs.

[This corrects the article DOI: 10.1371/journal.pbio.1001090.].

The introduction of tyrosine-kinase inhibitors (TKI) targeting specific EGFR mutations for the treatment non-small cell lung cancer patients (NSCLC) dramatically increased the clinical outcome in a subset of patients harboring specific activating EGFR mutations. Three different generations of TKI have been developed until now, demonstrating increasing progression-free survival as well as overall survival. However, to benefit of the treatment, the analysis of the genomic content of each patient is mandatory. Additionally, resistance mutations are prevalent and occur frequently and rapidly during treatment. Therefore, tests to detect EGFR mutations at initial diagnosis as well as during treatment, e.g., from liquid biopsies, have been developed and implemented in clinical daily practice for theranostic purpose.As EGFR mutation testing has to be highly reliable, fast, and easy to perform, the automatic qPCR system Idylla™ has been developed and implemented for clinical mutation testing from tissue samples and soon from circulating free DNA. Therefore, we here describe how the Idylla™ system can be used for the analysis of EGFR mutations in NSCLC patients. Importantly, as the results are massively influenced by the preanalytical steps, we also provide information on the correct sample selection to avoid nonconclusive results.

International audience

Rationale: Given the paucity of effective treatments for idiopathic pulmonary fibrosis (IPF), new insights into the deleterious mechanisms controlling lung fibroblast activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies. TGF-β (transforming growth factor-β) is the main profibrotic factor, but its inhibition is associated with severe side effects because of its pleiotropic role. Objectives: To determine if downstream noncoding effectors of TGF-β in fibroblasts may represent new effective therapeutic targets whose modulation may be well tolerated. Methods: We investigated the whole noncoding fraction of TGF-β-stimulated lung fibroblast transcriptome to identify new genomic determinants of lung fibroblast differentiation into myofibroblasts. Differential expression of the long noncoding RNA (lncRNA) DNM3OS (dynamin 3 opposite strand) and its associated microRNAs (miRNAs) was validated in a murine model of pulmonary fibrosis and in IPF tissue samples. Distinct and complementary antisense oligonucleotide-based strategies aiming at interfering with DNM3OS were used to elucidate the role of DNM3OS and its associated miRNAs in IPF pathogenesis. Measurements and Main Results: We identified DNM3OS as a fibroblast-specific critical downstream effector of TGF-β-induced lung myofibroblast activation. Mechanistically, DNM3OS regulates this process in trans by giving rise to three distinct profibrotic mature miRNAs (i.e., miR-199a-5p/3p and miR-214-3p), which influence SMAD and non-SMAD components of TGF-β signaling in a multifaceted way. In vivo, we showed that interfering with DNM3OS function not only prevents lung fibrosis but also improves established pulmonary fibrosis. Conclusions: Pharmacological approaches aiming at interfering with the lncRNA DNM3OS may represent new effective therapeutic strategies in IPF.

International audience; Commonly, circulating tumor cells (CTCs) are described as source of metastasis in cancer patients. However, in this process cancer cells of the primary tumor site need to survive the physical and biological challenges in the blood stream before leaving the circulation to become the seed of a new metastatic site in distant parenchyma. Most of the CTCs released in the blood stream will not resist those challenges and will consequently fail to induce metastasis. A few of them, however, interact closely with other blood cells, such as neutrophils, platelets, and/or macrophages to survive in the blood stream. Recent studies demonstrated that the interaction and modulation of the blood microenvironment by CTCs is pivotal for the development of new metastasis, making it an interesting target for potential novel treatment strategies. This review will discuss the recent research on the processes in the blood microenvironment with CTCs and will outline currently investigated treatment strategies.

Introduction The detection of a ROS1 rearrangement in advanced and metastatic lung adenocarcinoma (LUAD) led to a targeted treatment with tyrosine kinase inhibitors with favorable progression-free survival and overall survival of the patients. Thus, it is mandatory to screen for the ROS1 rearrangement in all these patients. ROS1 rearrangements can be detected using break-apart fluorescence in situ hybridization (FISH), which is the gold standard; however, ROS1 immunohistochemistry (IHC) can be used as a screening test because it is widely available, easy and rapid to perform, and cost-effective. Methods We evaluated the diagnostic accuracy and interpathologist agreement of two anti-ROS1 IHC clones, SP384 (Ventana, Tucson, Arizona) and D4D6 (Cell Signaling, Danvers, Massachusetts), in a training cohort of 51 positive ROS1 FISH LUAD cases, and then in a large validation cohort of 714 consecutive cases of LUAD from six routine molecular pathology platforms. Results In the two cohorts, the SP384 and D4D6 clones show variable sensitivity and specificity rates on the basis of two cutoff points greater than or equal to 1+ (all % tumor cells) and greater than or equal to 2+ (>30% stained tumor cells). In the validation cohort, the D4D6 yielded the best accuracy for the presence of a ROS1 rearrangement by FISH. Interpathologist agreement was moderate to good (interclass correlation 0.722–0.874) for the D4D6 clone and good to excellent (interclass correlation: 0.830–0.956) for the SP384 clone. Conclusions ROS1 IHC is an effective screening tool for the presence of ROS1 rearrangements. However, users must be acutely aware of the variable diagnostic performance of different anti-ROS1 antibodies before implementation into routine clinical practice.

International audience; The emergence of immunotherapy in oncology requires the discovery, validation and subsequent adoption of robust, sensitive and specific predictive and prognostic biomarkers for daily practice. Until now, anti-PD-L1 immunohistochemistry (IHC) on tissue sections has been the only validated companion diagnostic test for first-line immunotherapy for advanced and metastatic cancer, notably non-small-cell lung cancer (NSCLC). However, detection of this biomarker presents limitations that have stimulated the development of other biomarkers and other approaches. Within this context, the use of a liquid biopsy (LB) could provide an important complementary or alternative added value to PD-L1 IHC. In this review, we discuss how LBs have been used in the field of immuno-oncology (I-O) to predict response, relapse or adverse advents for patients undergoing immune-checkpoint inhibitor (ICI) therapy (anti-PD-1/PD-L1 and CTLA-4) and we highlight recent developments. Circulating tumor cells (CTCs), cell-free DNA (cfDNA), proteins and cytokines detected in plasma as well as circulating T-lymphocytes are discussed as potential sources for developing new I-O biomarkers. The quantification of cfDNA as a predictive biomarker, as well as its sequencing for the determination of tumor mutational burden, is already well advanced. Additionally, the quantification of PD-L1 from CTCs, bound on exosomes or free in plasma, as well as the determination of cytokines, are also being actively investigated with promising results having recently been published. Lastly, analysis of T-lymphocytes, especially by analyzing the T-cell receptor, has recently emerged as a valuable biomarker that might become relevant for the prediction of response to ICIs. While LBs have not yet been implemented in routine I-O clinical practice, recent promising data and rapidly advancing technologies indicate that this approach has the potential to soon personalize the clinical management of cancer patients receiving ICIs.

International audience; Companion diagnostic tests (CDXs) are considered mandatory for decision-making for treatment with targeted therapies in thoracic oncology. The emergence of immunotherapy has also given rise to the development of CDXs. Some CDXs, in particular PD-L1 immunohistochemistry tests, have been questioned and re-examined for use with new combination therapies that are being evaluated in clinical trials. Current questions include: Can we establish therapeutic indications in thoracis oncology without CDXs? Would the addition of new tests benefit patient outcome? Areas covered: This review covers the use of CDXs for decision-making in the treatment of lung cancer but also covers the limits of certain tests. It discusses the major challenges for present and future development of CDXs in daily practice. Expert opinion: CDXs can predict the efficacy of drugs if crucial steps in development and validation are fully controlled. Future development of CDXs must consider the detection of biomarkers of resistance and toxicity that are complementary to CDXs predicting therapeutic drug efficacy. Certain CDXs that have already been developed may be of interest for new indications in the field of thoracic oncology.

Histopathology is the fundamental tool of pathology used for more than a century to establish the final diagnosis of lung cancer. In addition, the phenotypic data contained in the histological images reflects the overall effect of molecular alterations on the behavior of cancer cells and provides a practical visual reading of the aggressiveness of the disease. However, the human evaluation of the histological images is sometimes subjective and may lack reproducibility. Therefore, computational analysis of histological imaging using so-called “artificial intelligence” (AI) approaches has recently received considerable attention to improve this diagnostic accuracy. Thus, computational analysis of lung cancer images has recently been evaluated for the optimization of histological or cytological classification, prognostic prediction or genomic profile of patients with lung cancer. This rapidly growing field constantly demonstrates great power in the field of computing medical imaging by producing highly accurate detection, segmentation or recognition tasks. However, there are still several challenges or issues to be addressed in order to successfully succeed the actual transfer into clinical routine. The objective of this review is to emphasize recent applications of AI in pulmonary cancer pathology, but also to clarify the advantages and limitations of this approach, as well as the perspectives to be implemented for a potential transfer into clinical routine., L’histopathologie est l’outil fondamental utilisé en anatomopathologie depuis plus d’un siècle pour établir le diagnostic final d’un carcinome bronchopulmonaire. L’information phénotypique présente sur les images histologiques reflète l’effet global des altérations moléculaires sur le comportement des cellules cancéreuses et fournit une lecture visuelle pratique de l’agressivité de la maladie. Cependant, l’évaluation humaine de l’image histologique peut être parfois subjective et assez peu reproductible selon les cas. Par conséquent, l’analyse computationnelle de l’imagerie histologique via des approches dites « d’intelligence artificielle » (IA) a récemment reçu une attention considérable afin d’améliorer cette précision diagnostique. Ainsi, l’analyse computationnelle d’images de cancer du poumon a récemment été évaluée pour l’optimisation de la classification histologique ou cytologique, la prédiction du pronostic ou du profil génomique des patients atteints d’un cancer pulmonaire. Ce domaine, en pleine croissance, fait constamment preuve d’une grande puissance dans le domaine de l’informatique d’imagerie médicale en produisant des tâches de détection, de segmentation ou de reconnaissance d’une très grande précision. Cependant, il subsiste plusieurs défis ou enjeux majeurs à relever afin de réussir le transfert réel de cette nouvelle approche en routine clinique. L’objectif de cette revue est de faire le point sur les applications récentes de l’IA en pathologie cancéreuse pulmonaire, mais aussi d’apporter des clarifications sur les avantages et les limites de cette approche, ainsi que les perspectives à mettre en œuvre pour un transfert potentiel dans la pratique quotidienne des pathologistes.

National audience; Tumor banks are asked to clinical and translationnal research project development in oncology. They strongly participate to the assessment, then to the validation of diagnostic, prognostic and predictive biomarkers. The progressive change of these structures leads to induce a professionalization of their functioning and to identify them as key actors in oncology by the stakeholders of the public and private worlds. The progresses made in biotechnologies and therapeutics are rapidly modifying the impact and the proper functioning of the biobanks. These latter are now facing different challenges, in particular for their sustainability. Among the major issues, the integration of the clinical and biological data becoming increasingly complex leads to urgently consider an optimization of the role of different biobanks in France. Their goal is to be an attractive counterpart face to the international competition. The purpose of this review is to briefly describe the current evolution of the biobanks, then their present and future challenges, and finally the role made by the pathologists in these new issues in oncology field.

Background Management of large numbers of reverse transcriptase-polymerase chain reactions (RT-PCR) for diagnosis of coronavirus 2019 disease (COVID-19) requires robust infrastructures, located in dedicated premises with a high standard of biosafety procedures, and well-trained personnel. The handling of a "run-of-river sample" to obtain rapid reporting of results is challenging. Methods We studied the clinical performance of the Idylla™ SARS-CoV-2 Test (index test) on a platform capable of fully automated nucleic acid testing including extraction, amplification, and detection in a single-use cartridge to establish the diagnosis of COVID-19. The study was conducted on a prospective cohort of 112 volunteers with recent symptoms and an unknown SARS-CoV-2 status who came to free screening centers of the Nice metropolitan area. All subjects underwent bilateral nasopharyngeal sampling. One sample was processed using the index test, the other using the standard of care RT-PCR. Samples were treated blind. Results Most of the participants (70%) were sampled within 4 days of symptom onset. Forty-five (40.2%) were positive for COVID-19. No clinical symptoms were distinguished between SARS-CoV-2 RT-PCR positive and negative subjects except anosmia and dysgeusia. Positive and negative agreement between the index and the standard of care test was 100%. Conclusions The Idylla™ SARS-CoV-2 Test is very sensitive, specific, rapid and easy to use in a near-patient RT-PCR approach to distinguish between symptomatic SARS-CoV-2 positive and negative patients in selected settings.

Simple Summary Screening for genomic alterations in treatment-naïve non-small cell lung carcinoma (NSCLC) is mainly done by tissue biopsy (TB), an invasive approach. However, it may not be possible to obtain a TB, the patient does not consent to it and/or the extracted nucleic acids are of poor quantity and/or quality for further genomic analyses, so a liquid biopsy (LB) is the only option to detect molecular target(s) for first-line treatment in these patients. However, a LB at diagnosis is still not often used in clinical centers since a TB is currently the gold standard approach for histological diagnosis, assessment of the PD-L1 status on tumor cells and evaluation of the molecular alterations. A number of different approaches are already available for the assessment of genetic abnormalities with LB, but next-generation sequencing (NGS) is the most promising. This review provides an overview of the main studies currently using LB NGS at diagnosis for NSCLC. We discuss its advantages and limitations in comparison with a TB and the perspectives for the future. Abstract Recently, the liquid biopsy (LB), a non-invasive and easy to repeat approach, has started to compete with the tissue biopsy (TB) for detection of targets for administration of therapeutic strategies for patients with advanced stages of lung cancer at tumor progression. A LB at diagnosis of late stage non-small cell lung carcinoma (NSCLC) is also being performed. It may be asked if a LB can be complementary (according to the clinical presentation or systematics) or even an alternative to a TB for treatment-naïve advanced NSCLC patients. Nucleic acid analysis with a TB by next-generation sequencing (NGS) is gradually replacing targeted sequencing methods for assessment of genomic alterations in lung cancer patients with tumor progression, but also at baseline. However, LB is still not often used in daily practice for NGS. This review addresses different aspects relating to the use of LB for NGS at diagnosis in advanced NSCLC, including its advantages and limitations.

The demand for expertise in pathology for the diagnosis of infectious diseases (ID) is continually growing, due to an increase in ID in immunocompromised patients and in the (re)-emergence of common and uncommon diseases, including tropical infections and infections with newly identified microbes. The microbiology laboratory plays a crucial role in diagnosing infections, identifying the responsible infectious agents and establishing sensitivity of pathogens to drug therapy. Pathology, however, is the only way to correlate the presence of an infectious agent with the reaction it evokes at cell and tissue level. For pathologists working in the field of ID pathology, it is essential to dispose of competence in cell and tissue pathology as well as in microbiology. Expertise in ID includes understanding of taxonomy and classification of pathogens as well as morphological criteria supporting their identification. Moreover, ID pathologists must master the methods used to detect pathogens in fixed cell and tissue samples, notably immunohistochemistry, in situ hybridization and the polymerase chain reaction. Paradoxically, the increasing frequency of lesions caused by pathogens and diagnosed in a pathology laboratory appears to be paralleled by a gradual loss of expertise of pathologists in the field of infectious and tropical diseases. We contend that this may be due at least in part to the continuously increasing number of samples of tumor tissue pathologists deal with and the rapidly expanding number of tissue based biomarkers with predictive value for new anti-cancer therapies. In this review, we highlight current and future issues pertaining to ID pathology, in order to increase awareness of its importance for surgical and molecular pathology. The intention is to contribute to the development of best practice in ID pathology.

Resume Les tests d’evaluation du statut PD-L1 realises en immunohistochimie sont proposes dans les essais cliniques en oncologie thoracique afin de predire la reponse aux immunotherapies ciblant l’axe PD-1/PD-L1. Avec l’arrivee de cette nouvelle classe de molecules en deuxieme ligne et tres rapidement en premiere ligne dans le traitement des patients atteints d’un cancer pulmonaire non a petites cellules de stade avance ou metastatique, ces tests devront certainement etre realises en routine des l’obtention de l’autorisation de mise sur le marche de ces traitements. La mise en place tres rapide de tests « compagnons » ou « complementaires » semble indispensable pour selectionner les patients devant beneficier de ces therapeutiques efficaces mais aussi couteuses et parfois toxiques. Bien que contestee (en particulier du fait que certains patients n’exprimant pas PD-L1 puissent parfois repondre aux therapeutiques ciblant l’axe PD1/PD-L1), l’approche immunohistochimique anti-PD-L1 parait incontournable en 2017. Cette nouvelle activite deployee dans les laboratoires d’ACP souleve desormais plusieurs questions : quel clone anti-PD-L1 utiliser ? Sur quel automate ? Quel seuil de positivite doit-on considerer ? Faut-il evaluer le marquage PD-L1 sur les cellules tumorales mais aussi sur les cellules immunitaires ? Quels controles doit-on utiliser ? Des etudes comparatives sont en cours ou ont ete deja realisees afin de pouvoir repondre a certaines de ces questions. Cette revue aborde les differents criteres d’evaluation immunohistochimique des principaux anticorps anti-PD-L1 utilises a ce jour et les travaux realises recemment utilisant ces anticorps en oncologie thoracique.

Resume L’activite des laboratoires d’anatomo-cyto-pathologie (ACP) s’est considerablement modifiee ces dernieres annees en raison de l’evolution des pratiques cliniques et des progres therapeutiques. Ainsi, par exemple, le developpement des therapies ciblees et de l’immunotherapie a recemment bouleverse la prise en charge des echantillons tissulaires et cytologiques, mais aussi des echantillons sanguins a visee diagnostique, pronostique et predictive de reponse aux nouvelles therapies. Dans ce contexte, il est devenu essentiel d’optimiser les bonnes pratiques dans les laboratoires d’ACP, afin d’assurer une offre de soins de qualite en collaboration etroite avec les cliniciens. Si la plupart des pays industrialises ont mis en place depuis plusieurs annees un systeme d’accreditation dans les laboratoires d’ACP, ceci n’est pas, ou peu, le cas en France. La norme d’accreditation applicable en France pour les laboratoires d’analyse medicale est la norme ISO 15189. Cette accreditation est delivree par un organisme, le COFRAC (comite francais d’accreditation), apres audit de la structure. Si cette norme est bien adaptee aux pratiques de la biologie medicale, elle est souvent discutable pour les pathologistes. Il est neanmoins incontournable de s’engager rapidement dans une demarche d’accreditation pour les laboratoires d’ACP en France afin de repondre aux nouvelles exigences de la pathologie clinique et moleculaire et notamment pour rester competitif en Europe. Cette revue aborde les enjeux actuels et futurs de l’accreditation des laboratoires d’ACP en France mais aussi les principales contraintes et potentielles faiblesses de la norme ISO 15189 dans le cadre des activites de l’ACP.

Resume Les biobanques ou centres de ressources biologiques (CRB) sont les maillons essentiels de la recherche translationnelle. Ces structures beneficient de financements publics recurrents afin d’etablir des collections d’echantillons biologiques utilisees dans le cadre de projets de recherche. Plus de 100 biobanques ont ete developpees sur le territoire national au sein des hopitaux universitaires et des centres de lutte contre le cancer. Le developpement de nouvelles techniques et de nouvelles methodes d’analyses dans la recherche medicale bouleversent les pratiques et soulevent de nouveaux defis scientifiques et organisationnels dans la collecte, la transformation et la conservation des echantillons. Relever ces defis devient un enjeu primordial pour les biobanques. La mise en place d’une strategie dynamique pour anticiper les besoins des utilisateurs est necessaire et repose sur de nouveaux modes de fonctionnement. Cet article decrit les enjeux a court et a moyen terme pour les biobanques francaises et propose des elements d’organisation pour y repondre.