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Véronique Hofman,
Marius Ilie,
Elodie Long-Mira,
Damien Giacchero, Catherine Butori,
Bérengère Dadone,
Eric Selva,
Virginie Tanga,
Thierry Passeron,
Gilles Poissonnet,
Jean-François Emile,
Jean-Philippe Lacour,
Philippe Bahadoran,
Paul Hofman
Journal of Investigative Dermatology 01/2013; · 6.31 Impact Factor
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Histopathology 05/2012; 61(3):519-22. · 3.08 Impact Factor
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Véronique Hofman,
Marie-Clotilde Gaziello,
Christelle Bonnetaud,
Marius Ilie,
Virginie Mauro,
Elodie Long,
Eric Selva,
Virginie Gavric-Tanga,
Sandra Lassalle, Catherine Butori,
Caroline Papin-Michaud,
Nathalie Lerda,
Olivier Bordone,
Céline Coelle,
Jean-Christophe Sabourin,
Christian Chabannon,
Paul Hofman
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ABSTRACT: The biobanking area is highly complex, and its complexity is increasing along with its growth and demand. Due to the advancements in genetic research, stem cell research and regenerative medicine, biobanking has become ever more important and plays a key role in biomedical research. The robustness and the reproducibility of research results depend greatly on the quality and on the number of the samples used, and thus on the expertise of biobanks having supplied these samples. Undoubtedly, the recognition of a research biobank depends on the impact of the research projects conducted with samples obtained from tumour bank(s), but also on many other criteria. It thus seems important to determine a number of indicators within a biobank to estimate objective criteria for the performance of these structures. These indicators can allow to make some strategic decisions knowing that biobanks are expensive structures to maintain in the present hospital context. The use of these indicators could also contribute to the elaboration of an "biobank impact factor of" or so called "bioresource research impact factor" (BRIF). We describe here four major categories of indicators (quality, activity, scientific production, visibility), which seem to be useful for the evaluation of a biobank by making a proposition of allocation of coefficients for the various considered items.
Annales de Pathologie 04/2012; 32(2):91-101. · 0.25 Impact Factor
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ABSTRACT: Salivary gland tumors in children are rare: they correspond to 8-10% of head and neck pediatric tumors. Clinicians of all disciplines should be aware of this diagnosis in front of non-inflammatory mass of the parotid or in the territory of other salivary glands. In children, 50% of salivary gland tumors are malignant which contrasts with a 10-25% risk in adults. Epithelial tumors are the most common, mucoepidermoïd carcinomas of the parotid in particular. Surgery is the treatment of choice in epithelial tumors. Adjuvant radiotherapy may be indicated in case of unfavorable prognostic factors but must be balanced with the risk of radiation-induced growth defects and secondary cancer. The role of chemotherapy is limited in these tumors, but should be discussed in case of an inoperable or metastatic lesion.
Bulletin du cancer 06/2011; 98(7):847-55. · 0.67 Impact Factor
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ABSTRACT: We report here the existence of a novel subset of langerin (CD207)-positive, immature dendritic cells (DCs) (CD83(neg) ) abundantly infiltrating Epstein Barr virus (EBV)-infected areas in tonsil, Hodgkin lymphoma and nasopharyngeal carcinoma. These CD207(+) DCs differ from conventional epidermal Langerhans cells in their lack of CD1a and CCR6 and their unusual tissue localization. CD207(+) DC infiltration strongly correlates with EBV infection because it was neither detected in EBV negative specimens nor in tissues infected with other human viruses. These immature DCs might represent good candidates for induction of the EBV-specific immune response.
International Journal of Cancer 05/2011; 128(10):2501-8. · 5.44 Impact Factor
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Véronique Hofman,
Christelle Bonnetaud,
Marius I Ilie,
Philippe Vielh,
Jean Michel Vignaud,
Jean François Fléjou,
Sylvie Lantuejoul,
Eric Piaton,
Nadine Mourad, Catherine Butori,
Eric Selva,
Michel Poudenx,
Stéphanie Sibon,
Sabrina Kelhef,
Nicolas Vénissac,
Jean-Philippe Jais,
Jérôme Mouroux,
Thierry Jo Molina,
Paul Hofman
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ABSTRACT: Pathologic TNM staging is currently the best prognostic factor for non-small cell lung carcinoma (NSCLC). However, even in early-stage NSCLC, the recurrence rates after surgery range from 25% to 50%. The preoperative detection of circulating tumor cells (CTC) could be useful to tailor new therapeutic strategies in NSCLC. We assessed the presence of CTC in NSCLC patients undergoing surgery, using cytologic analyses, after their isolation by size of epithelial tumor cells (ISET method). The presence and the number of CTCs were considered and correlated with clinicopathologic parameters including patient follow-up.
Of the 247 blood samples tested, 208 samples were from patients with resectable NSCLC and 39 from healthy subjects. The mean follow-up was 24 months. An image of detected cells with presumably nonhematologic features [initially defined as "circulating nonhematologic cells" (CNHC)] was recorded. The presence of CNHC was assessed blindly and independently by 10 cytopathologists, using cytologic criteria of malignancy on stained filters. The count of detected CNHCs was made for each filter.
One hundred two of 208 (49%) patients showed CNHCs corresponding to CNHC with malignant cytopathologic features in 76 of 208 (36%) cases. CNHCs were not detected in the control group. A level of 50 or more CNHCs corresponding to the third quartile was associated with shorter overall and disease-free-survival, independently of disease staging, and with a high risk of recurrence and death in early-stage I + II-resectable NSCLC.
A high percentage of NSCLC patients show preoperative detection of CNHC by the ISET method. The presence and level of 50 or more CNHCs are associated with worse survival of patients with resectable NSCLC.
Clinical Cancer Research 02/2011; 17(4):827-35. · 7.74 Impact Factor
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Véronique J Hofman,
Marius I Ilie,
Christelle Bonnetaud,
Eric Selva,
Elodie Long,
Thierry Molina,
Jean Michel Vignaud,
Jean François Fléjou,
Sylvie Lantuejoul,
Eric Piaton, [......],
Nathalie Mourad,
Michel Poudenx,
Philippe Bahadoran,
Stéphanie Sibon,
Nicolas Guevara,
José Santini,
Nicolas Vénissac,
Jérôme Mouroux,
Philippe Vielh,
Paul M Hofman
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ABSTRACT: Detection of circulating tumor cells (CTCs) morphologically may be a promising new approach in clinical oncology. We tested the reliability of a cytomorphologic approach to identify CTCs: 808 blood samples from patients with benign and malignant diseases and healthy volunteers were examined using the isolation by size of epithelial tumor cell (ISET) method. Cells having nonhematologic features (so-called circulating nonhematologic cells [CNHCs]) were classified into 3 categories: CNHCs with malignant features, CNHCs with uncertain malignant features, and CNHCs with benign features. CNHCs were found in 11.1% and 48.9% of patients with nonmalignant and malignant pathologies, respectively (P < .001). CNHCs with malignant features were observed in 5.3% and in 43.1% of patients with nonmalignant and malignant pathologies, respectively. Cytopathologic identification of CTCs using the ISET method represents a promising field for cytopathologists. The possibility of false-positive diagnosis stresses the need for using ancillary methods to improve this approach.
American Journal of Clinical Pathology 01/2011; 135(1):146-56. · 2.60 Impact Factor
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Véronique Hofman,
Christelle Bonnetaud,
Marie Clotilde Gaziello,
Marius Ilie,
Sandra Lassalle, Catherine Butori,
Nathalie Lerda,
Eric Selva,
Virginie Gavric-Tanga,
Laurent Castillo,
Nicolas Guevara,
José Santini,
Daniel Pop,
Nicolas Vénissac,
Jérôme Mouroux,
Christian Chabannon,
Paul Hofman
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ABSTRACT: Over the last 10 years, significant financial support from the French National Institute of Cancer (INCa), the Ministry of Health (DGOS), and the Health and Research National Institute (Inserm) helped biobanks--of which tumour banks represent a prominent example of hospital-based infrastructures--to improve their operations, and in some instances to adopt the rules of Biological Ressource Centers as defined by OECD. Nowadays, the use of biological samples of human origin is strictly subordinated to regulations that integrate bioethical principles. However, in spite of the establishment of these regulations, requirement to obtain an authorisation and/or to register the biological collections with the Ministry of Research, many uncertainties persist. While French regulations mandate that samples can be used for research as long as patients did not oppose to such use, many biobank curators face practical and theoretical issues when establishing a Material Transfer Agreement with scientists, due to the lack of harmonization between national regulations--particularly due to a different perception of privacy and free will in anglo-american and other countries--and different demands on the side of private industry or editorial boards of scientific journals. The goal of this article is (1) to describe the procedure followed to collect patients' informed consent at the Biobank of CHU de Nice and (2) to assess the number of obtained consents in comparison to the number of collected samples between 01/09/2004 and 31/12/2009, the number of consents obtained before or after collecting the samples, and the number of patients' refusal to collect their biological resources. This balance-sheet is settled for the three major collections (thoracic, thyroid and head and neck tissues) from the Biobank of CHU de Nice. Results show that 88 % of consents were obtained during this period (82 % in a prospective manner and 6 % in a retrospective manner). Refusal was notified by writing in nine cases only. The percentage of consents varies slightly according to the collection involved and is stable from 2004 to 2009. Overall, our procedure is quite efficient at obtaining informed consents from a majority of patients for whom the tumour bank stores biological samples. This situation provides optimal conditions for the use of collected samples in the context of national and international research projects.
Annales de Pathologie 10/2010; 30(5):337-43. · 0.25 Impact Factor
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ABSTRACT: In the last decades, several ancillary methods, such as immunohistochemistry and molecular biology techniques, have increased the possibilities for the diagnosis and to evaluate the prognosis of lesions observed in a laboratory of pathology. Conversely, the impact of another method largely used a couple of years ago in a laboratory of pathology, the electron microscopy (EM), is currently limited. EM is a difficult, quite expensive and long method, which requires technicians with a high qualification. Therefore, EM is currently rarely available at the hospital in a laboratory of pathology and is essentially established in research centers. However, EM is still an essential tool for the surgical pathologist. This method allows in some circumstances to confirm or, more rarely, to make the diagnosis of a couple of tissular and cellular lesions observed in human pathology. EM is also an interesting method to better understand the etiopathogenesis of emerging human diseases, in particular of emerging infectious diseases. In this review, we report the main indication of EM in human pathology, we lay special emphasize in certain infectious diseases and neoplasia.
Annales de Pathologie 08/2010; 30(4):263-72. · 0.25 Impact Factor
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ABSTRACT: Fat cell accumulation in skeletal muscle is a major characteristic of various disorders, such as obesity, sarcopenia and dystrophies. Moreover, these fat cells could be involved in muscle homeostasis regulation as previously described for adipocytes in bone marrow. Despite recent advances on the topic, no clearly characterized mouse model is currently available to study fat accumulation within skeletal muscle. Here, we report a detailed characterization of a mouse model of skeletal muscle fat cell accumulation after degeneration induced by intra-muscular injection of glycerol. Information is provided on the kinetics of degeneration/fat deposition, including the quantity of fat deposited based on various parameters such as glycerol concentration, age, sex and strain of mice. Finally, these fat cells are characterized as true white adipocytes morphologically and molecularly. Our study shows that the mouse adipocyte accumulation within skeletal muscle after glycerol degeneration is a reproducible, transposable and easy model to use. This mouse model should allow a more comprehensive understanding of the impact of adipocyte accumulation in skeletal muscle pathophysiology.
Biochemical and Biophysical Research Communications 06/2010; 396(3):767-73. · 2.48 Impact Factor
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Véronique Hofman,
Marius Ilie,
Virginie Gavric-Tanga,
Virgine Lespinet,
Mireille Mari,
Sandra Lassalle, Catherine Butori,
Céline Coelle,
Olivier Bordone,
Eric Selva,
Aude Lamy,
Jean-Christophe Sabourin,
Paul Hofman
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ABSTRACT: The advent of the targeted cancer therapies administered to patients, according to the results of molecular biology techniques (in particular, in situ hybridization, "polymerase chain reaction" amplification and sequencing), has modified the practice of the surgical pathology laboratories. The necessity to answer to the needs of physicians for optimizing the medical care for patients who develop cancer has led to a policy of national debate, spurred by the National Institute of Cancer (INCa), in order to implement new procedures in the pathology laboratories. Thus, in addition to the structuring of molecular biology platforms and their labeling by INCa, the upstream control of the steps present between resection of tumor samples and molecular analysis has proved to be crucial. Indeed, the quality of this upstream time, called "pre-analytical" phase, determines the reliability of the molecular biology results and therefore the therapeutic strategy. We describe here the main steps to be checked in the pre-analytical phase. The optimization of this pre-analytical phase within the surgical pathology laboratory aims to reduce or render insignificant the risk of errors of molecular biology tests. These errors can indeed lead to false negative or false positive results whose therapeutic consequences can be particularly harmful to patients with cancer.
Annales de Pathologie 04/2010; 30(2):85-93. · 0.25 Impact Factor
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ABSTRACT: A BRAF somatic mutation at residue 600 of the BRAF protein (BRAFV600E) is highly prevalent in papillary thyroid carcinomas (PTC). This mutation occurs in approximately 44% (from 29% to 83%) of PTC depending on the different studies. BRAFV600E is almost always found in PTC with a papillary or a mixed follicular/papillary architecture, being rarer in other subtypes of PTC. The discovery of the BRAFV600E mutation in tissue and fine-needle aspiration (FNA) is diagnostic for PTC and has been frequently associated with worse clinical prognosis. However, some studies failed to reveal this prognostic association. Transcriptional and post-transcriptional modulation of PTC with a BRAF mutation has been evaluated in some recent studies. Current therapeutic approaches targeting BRAF are being tested in clinical trials, particularly in more aggressive PTC. In this review, we will first discuss the diagnostic value of a BRAF mutation for PTC diagnosis. The prognostic role of a BRAFV600E mutation is then outlined and discussed in the context of other well-accepted clinicopathological prognostic parameters for PTC (age, gender, pTNM stage, histological subtype). Finally, the currently and potentially used treatments targeting BRAF in patients with PTC are presented.
Current Medicinal Chemistry 03/2010; 17(17):1839-50. · 4.86 Impact Factor
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Didier F Pisani,
Claude A Dechesne,
Sabrina Sacconi,
Severine Delplace,
Nathalie Belmonte,
Olivia Cochet,
Noémie Clement,
Brigitte Wdziekonski,
Albert P Villageois, Catherine Butori,
Claude Bagnis,
James P Di Santo,
Jean-Yves Kurzenne,
Claude Desnuelle,
Christian Dani
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ABSTRACT: The differentiation of multipotent cells into undesirable lineages is a significant risk factor when performing cell therapy. In muscular diseases, myofiber loss can be associated with progressive fat accumulation that is one of the primary factors leading to decline of muscular strength. Therefore, to avoid any contribution of injected multipotent cells to fat deposition, we have searched for a highly myogenic but nonadipogenic muscle-derived cell population. We show that the myogenic marker CD56, which is the gold standard for myoblast-based therapy, was unable to separate muscle cells into myogenic and adipogenic fractions. Conversely, using the stem cell marker CD34, we were able to sort two distinct populations, CD34(+) and CD34(-), which have been thoroughly characterized in vitro and in vivo using an immunodeficient Rag2(-/-)gamma(c) (-/-) mouse model of muscle regeneration with or without adipose deposition. Our results demonstrate that both populations have equivalent capacities for in vitro amplification. The CD34(+) cells and CD34(-) cells exhibit equivalent myogenic potential, but only the CD34(-) population fails to differentiate into adipocytes in vitro and in vivo after transplantation into regenerative fat muscle. These data indicate that the muscle-derived cells constitute a heterogeneous population of cells with various differentiation potentials. The simple CD34 sorting allows isolation of myogenic cells with no adipogenic potential and therefore could be of high interest for cell therapy when fat is accumulated in diseased muscle.
Stem Cells 02/2010; 28(4):753-64. · 7.78 Impact Factor
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ABSTRACT: Immunocompromised patients who develop invasive filamentous mycotic infections can be efficiently treated if rapid identification of the causative fungus is obtained. We report a case of fatal necrotic pneumonia caused by combined pulmonary invasive mucormycosis and aspergillosis in a 66 year-old renal transplant recipient. Aspergillus was first identified during the course of the disease by cytological examination and culture (A. fumigatus) of bronchoalveolar fluid. Hyphae of Mucorales (Rhizopus microsporus) were subsequently identified by culture of a tissue specimen taken from the left inferior pulmonary lobe, which was surgically resected two days before the patient died. Histological analysis of the lung parenchyma showed the association of two different filamentous mycoses for which the morphological features were evocative of aspergillosis and mucormycosis. However, the definitive identification of the associative infection was made by polymerase chain reaction (PCR) performed on deparaffinized tissue sections using specific primers for aspergillosis and mucormycosis. This case demonstrates that discrepancies between histological, cytological and mycological analyses can occur in cases of combined mycotic infection. In this regard, it shows that PCR on selected paraffin blocks is a very powerful method for making or confirming the association of different filamentous mycoses and that this method should be made available to pathology laboratories.
Diagnostic Pathology 01/2010; 5:1. · 1.64 Impact Factor
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Sandra Lassalle,
Véronique Hofman,
Ilie Marius,
Virginie Gavric-Tanga,
Patrick Brest,
Katia Havet, Catherine Butori,
Eric Selva,
José Santini,
Baharia Mograbi,
Paul Hofman
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ABSTRACT: With the advent of the formaldehyde standard law in France, and because of the impact of new methods for diagnosis and prognosis in pathology, formalin replacement in surgical pathology laboratories is currently being discussed in France. However, a set of criteria must be assessed before introducing a formalin substitute fixative. The objective of this study was to compare formalin substitute fixation with formalin fixation and cryoconservation of tissues from several benign and malignant thyroid pathologies with respect to morphology, antigenicity, and nucleic acid (RNA, DNA, microRNA) integrity.
Calibrated specimens (200 mg, 1 cm(2) each) from four conventional papillary thyroid carcinomas, four follicular variant of papillary thyroid carcinomas, three minimally invasive follicular carcinomas, four thyroid adenomas, five thyroid nodular hyperplasias, and five normal thyroid tissues were fixed for 6, 12, or 24 hours, in different fixatives (formalin, Glyo-Fixx, FineFIX, ExcellPlus, RCL2) at room temperature or at 4 degrees C. Tissues were stained (hematoxylin-eosin, periodic acid Schiff, trichromic Masson, and Sweet-Gordon staining) and their antigenicity determined by immunohistochemistry (performed with HBME-1, galectin-3, CK19, vimentin, CD31, and KL1 antibodies). Evaluation by four pathologists was made blinded. The quantity and quality of DNA, RNA, and two representative microRNA extracted from deparaffinized sections of paraffin embedded specimen were compared with that of cryosections.
The staining and morphology were not altered by the use of different fixatives. However, formalin, FineFIX, and RCL2 gave the best results for immunohistochemistry. Moreover, FineFIX and RCL2 gave the highest amount of nucleic acids and of the best quality.
All the formalin substitute fixatives used in this study provided good histomorphologic quality for the different stained thyroid tissues, but individually, some fixatives performed better for immunohistochemical and molecular biological procedures for different thyroid pathologies.
Thyroid: official journal of the American Thyroid Association 11/2009; 19(11):1239-48. · 2.60 Impact Factor
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ABSTRACT: A large variety of infectious diseases may involve the rhinosinusal tract. They include bacterial, viral, fungal, and parasite infections. These infections can induce an acute and/or a chronic inflammatory reaction. They can develop both in immunocompetent or in immunodeficient patients. Clinically, the consequences of these infections are variable, but a few of them have to be rapidly diagnosed for an immediate specific treatment. This article describes the pathologic features of a variety of infectious diseases that surgical pathologists may encounter in analysis of biopsy specimens taken from the rhinosinusal tract.
Annales de Pathologie 09/2009; 29(4):313-22. · 0.25 Impact Factor
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Véronique Hofman,
Sandra Lassalle,
Christelle Bonnetaud, Catherine Butori,
Céline Loubatier,
Marius Ilie,
Olivier Bordone,
Patrick Brest,
Nicolas Guevara,
José Santini,
Brigitte Franc,
Paul Hofman
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ABSTRACT: The term thyroid tumours of uncertain malignant potential (TT-UMP) has been proposed for a subgroup of follicular-patterned thyroid tumours for which benignancy or malignancy cannot be assessed with certainty. The frequency, diagnostic reproducibility, immunohistochemistry and molecular genetic profiling of such tumours have been poorly explored. We, therefore, investigated (1) the frequency of TT-UMP diagnosed in a single institution (Nice, France: 2004-2008), (2) the observer variation among four pathologists, (3) whether immunohistochemical and molecular genetic profiling of TT-UMP provide additional information concerning such lesions. A series of 31 diagnosed TT-UMP (2.9%) out of 1,078 consecutive thyroidectomies were analysed. It comprised 15 follicular thyroid tumours of UMP (FT-UMP) and 16 well-differentiated tumours of UMP (WDT-UMP). Observer concordance was 70% for all TT-UMP. More than 50% of FT-UMP expressed galectin-3 and CK19, whereas more than 50% of WDT-UMP expressed HBME-1. Five cases of TT-UMP showed N-RAS mutations, while one showed H-RAS mutation and another PAX8/PPARgamma rearrangement. In conclusion, the frequency of TT-UMP is low in our institution. Diagnostic reproducibility is within the same range as other published data on follicular-patterned thyroid tumours. The ancillary methods have a low impact on aiding diagnosis of such lesions.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2009; 455(1):21-33. · 2.49 Impact Factor
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Pathology 01/2009; 40(7):729-32. · 2.38 Impact Factor
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Pathology 11/2008; 40(7):729–732. · 2.38 Impact Factor
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ABSTRACT: Adenoid cystic carcinoma (ACC) occurs not only as a tumor of salivary glands, but also in very unusual locations, such as in the skin. Only very few cases of primary cutaneous of ACC have metastasized to the lymph nodes and lungs. We present a 53-year-old man with metastasis of the pericardium from a primary cutaneous ACC (PCACC) of the scalp, which had been surgically treated 14 years ago. Exfoliative cytologic findings from pericardial effusion included small clusters of basaloid cells with occasional cystlike spaces containing mucoid material. To our knowledge, this is the first case of pericardial metastasis from a PCACC.
Diagnostic Cytopathology 06/2008; 36(5):351-4. · 1.16 Impact Factor
