Pierre Raynaud

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (17)30.49 Total impact

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    ABSTRACT: Several studies have highlighted the importance of the microenvironment in the behaviour of follicular lymphoma (FL). We conducted an immunohistochemical analysis to assess the role of different cell subpopulations, i.e. CD8, CD68 and forkhead box protein P3 (FOXP3)-positive regulatory T cells (Treg cells) in 84 lymph nodes of 58 patients with FL (58 at diagnosis, 26 at relapse). Since the overall effect of Tregs is considered to depend on their number in relation to CD8(+) effector T cells, we determined the corresponding ratio for each patient and correlated the results with clinical parameters. The interfollicular CD8/FOXP3(+) cell ratio was significantly higher in patients with histological grade 3 tumours (2.04 vs. 1.63) and with a high risk FLIPI index (2.99 vs. 1.53) compared to those with grade 1-2 tumours or a low-intermediate FLIPI index. Similar results were obtained for the follicular CD8(+)/FOXP3(+) cell ratio. The interfollicular CD8/FOXP3 ratio was found to have prognostic value [a 5-year overall survival (OS) of 82 vs. 59% for a ratio of ±1.68]. In addition, an interfollicular FOXP3(+) cell number of more than 86 cells/mm(2) was correlated with a more favourable outcome (p=0.03). When patients at diagnosis and relapse were compared, a significant difference (p=0.05) in the localization (interfollicular vs. intrafollicular) of FOXP3(+) cells was observed. The CD8/FOXP3 ratio in the interfollicular areas was significantly different (1.66 at diagnosis vs. 2.2 at relapse, p=0.05). The presence of a small number of FOXP3(+) cells with a high CD8/FOXP3 ratio is probably the indicator of an active immune response during tumour development, with lymphoma cells acting as targets or bystanders.
    Experimental and therapeutic medicine 01/2010; 1(6):933-938. · 0.34 Impact Factor
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    ABSTRACT: Among primitive adenocarcinoma of nasal cavity and paranasal sinus, the 2005 WHO classification distinguishes two main categories: intestinal type adenocarcinoma (ITAC) and low-grade non-intestinal adenocarcinoma, entities with different clinical and epidemiological characteristics. Low-grade adenocarcinoma shows a respiratory type phenotype (CK20-/CK7+/CDX2-/villin-) and ITACs, an intestinal type profile (CK20+/CK7-/CDX2+/villin+). Because of histological, ultrastructural and phenotypical similarities between ITAC and colorectal adenocarcinomas, several studies have discussed a possible common pathway in carcinogenesis. But the review of literature shows conflicting results, suggesting different pathways of pathogenesis. Differential diagnoses of sinonasal intestinal-type adenocarcinoma are mainly respiratory epithelial adenomatoid hamartomas, inverted schneiderian papillomas, salivary glands-type carcinoma and more rarely metastasis of adenocarcinoma.
    Annales de Pathologie 09/2009; 29(4):286-95. · 0.24 Impact Factor
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    ABSTRACT: Among primitive adenocarcinoma of nasal cavity and paranasal sinus, the 2005 WHO classification distinguishes two main categories: intestinal type adenocarcinoma (ITAC) and low-grade non-intestinal adenocarcinoma, entities with different clinical and epidemiological characteristics. Low-grade adenocarcinoma shows a respiratory type phenotype (CK20-/CK7+/CDX2-/villin-) and ITACs, an intestinal type profile (CK20+/CK7-/CDX2+/villin+). Because of histological, ultrastructural and phenotypical similarities between ITAC and colorectal adenocarcinomas, several studies have discussed a possible common pathway in carcinogenesis. But the review of literature shows conflicting results, suggesting different pathways of pathogenesis. Differential diagnoses of sinonasal intestinal-type adenocarcinoma are mainly respiratory epithelial adenomatoid hamartomas, inverted schneiderian papillomas, salivary glands-type carcinoma and more rarely metastasis of adenocarcinoma.
    Annales De Pathologie - ANN PATHOL. 01/2009; 29(4):286-295.
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    ABSTRACT: Rituximab, an anti-CD20 monoclonal antibody, is widely used in the treatment of B-cell lymphoma. Some reports have outlined histologic modifications in bone marrow specimens from patients treated with this antibody, notably the presence of CD3(+) lymphoid aggregates morphologically mimicking residual lymphoma. To gain insight into the significance of such infiltrates, serial BM trephines obtained in 39 patients with B-cell follicular lymphoma treated by rituximab and enrolled in the GOELAMS-GELA intergroup FL2000 protocol were reexamined. The 39 patients were 22 women and 17 men with a median age of 50 years (range, 29-75 years). All pretreatment bone marrow biopsies showed CD20(+) lymphomatous cells. A second biopsy was obtained between 30 and 100 days after the last rituximab injection: 19 (48%) were morphologically diagnosed as negative (no lymphoid infiltrates or only minor lymphoid aggregates) and 20 (51%) as positive because of persistent lymphoid nodules. After immunohistochemical analysis, 13 (33%) cases were reinterpreted as false-positive because of the complete absence of CD20(+) cells, with the lymphoid nodules consisting of CD3(+) and CD5(+) T cells. Most of them also expressed CD4(+), whereas only a few CD8(+) cells were present. Among these 13 false-positive cases, 12 were BCL2-IGH polymerase chain reaction-negative in the bone marrow aspirate at the time of biopsy. The 13th case turned out to be negative in the 18th-month bone marrow aspirate. In all of these cases, lymphoid aggregates had disappeared on bone marrow biopsies performed 18 months after treatment. After a mean follow-up of 4.5 years, 9 of 13 patients were in remission as compared with only 2 among the 7 patients with postrituximab persistent CD20(+) lymphomatous cells. There was no statistically significant difference between this false-positive group of patients and that with negative postrituximab bone marrow regarding sex, age, medullar involvement pattern before treatment, delay between rituximab treatment, and molecular status. Interestingly, we noted a more favorable outcome (70% versus 52% remission) for the false-positive cases, suggesting that these T-cell reactions could be the hallmark of specific antitumoral immunity after rituximab treatment and should be properly investigated.
    Human Pathlogy 03/2008; 39(2):194-200. · 2.84 Impact Factor
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    ABSTRACT: The heparan sulfate (HS) proteoglycan, syndecan-1, plays a major role in multiple myeloma (MM) by concentrating heparin-binding growth factors on the surface of MM cells (MMCs). Using Affymetrix microarrays and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), we show that the gene encoding heparanase (HPSE), an enzyme that cleaves HS chains, is expressed by 11 of 19 myeloma cell lines (HMCLs). In HSPE(pos) HMCLs, syndecan-1 gene expression and production of soluble syndecan-1, unlike expression of membrane syndecan-1, were significantly increased. Knockdown of HPSE by siRNA resulted in a decrease of syndecan-1 gene expression and soluble syndecan-1 production without affecting membrane syndecan-1 expression. Thus, HPSE influences expression and shedding of syndecan-1. Contrary to HMCLs, HPSE is expressed in only 4 of 39 primary MMC samples, whereas it is expressed in 36 of 39 bone marrow (BM) microenvironment samples. In the latter, HPSE is expressed at a median level in polymorphonuclear cells and T cells; it is highly expressed in monocytes and osteoclasts. Affymetrix data were validated at the protein level, both on HMCLs and patient samples. We report for the first time that a gene's expression mainly in the BM environment (ie, HSPE) is associated with a shorter event-free survival of patients with newly diagnosed myeloma treated with high-dose chemotherapy and stem cell transplantation. Our study suggests that clinical inhibitors of HPSE could be beneficial for patients with MM.
    Blood 07/2007; 109(11):4914-23. · 9.06 Impact Factor
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    ABSTRACT: Cancer-testis (CT) Ags are expressed in testis and malignant tumors but rarely in nongametogenic tissues. Due to this pattern, they represent attractive targets for cancer vaccination approaches. The aims of the present study are: 1) to assess the expression of CT genes on a pangenomic base in multiple myeloma (MM); 2) to assess the prognosis value of CT gene expression; and 3) to provide selection strategies for CT Ags in clinical vaccination trials. We report the expression pattern of CT genes in purified MM cells (MMC) of 64 patients with newly diagnosed MM and12 patients with monoclonal gammopathy of unknown significance, in normal plasma cell and B cell samples, and in 20 MMC lines. Of the 46 CT genes interrogated by the Affymetrix HG-U133 set arrays, 35 are expressed in the MMC of at least one patient. Of these, 25 are located on chromosome X. The expression of six CT genes is associated with a shorter event-free survival. The MMC of 98% of the patients express at least one CT gene, 86% at least two, and 70% at least three CT genes. By using a set of 10 CT genes including KM-HN-1, MAGE-C1, MAGE-A3/6/12, MAGE-A5, MORC, DDX43, SPACA3, SSX-4, GAGE-1-8, and MAGE-C2, a combination of at least three CT genes-desirable for circumventing tumor escape mechanisms-is obtained in the MMC of 67% of the patients. Provided that the immunogenicity of the products of these 10 CT genes is confirmed, gene expression profiling could be useful in identifying which CT Ags could be used to vaccinate a given patient.
    The Journal of Immunology 04/2007; 178(5):3307-15. · 5.52 Impact Factor
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    ABSTRACT: Methacarn and RCL2, a new noncrosslinking fixative, were compared to formalin-fixed or frozen tissue samples of the same invasive breast carcinoma and were evaluated for their effects on tissue morphology and immunohistochemistry as well as DNA and RNA integrity. The histomorphology of methacarn- or RCL2-fixed paraffin-embedded tumors was similar to that observed with the matched formalin-fixed tissues. Immunohistochemistry using various antibodies showed comparable results with either fixative, leading to accurate breast tumor diagnosis and determination of estrogen and progesterone receptors, and HER2 status. Methacarn and RCL2 fixation preserved DNA integrity as demonstrated by successful amplification and sequencing of large DNA amplicons. Similarly, high-quality RNA could be extracted from methacarn- or RCL2-fixed paraffin-embedded MCF-7 cells, whole breast tumor tissues, or microdissected breast tumor cells, as assessed by electropherogram profiles and real-time reverse transcriptase-polymerase chain reaction quantification of various genes. Moreover, tissue morphology and RNA integrity were preserved after 8 months of storage. Altogether, these results indicate that methacarn, as previously shown, and RCL2, a promising new fixative, have great potential for performing both morphological and molecular analyses on the same fixed tissue sample, even after laser-capture microdissection, and can open new doors for investigating small target lesions such as premalignant breast lesions.
    Journal of Molecular Diagnostics 06/2006; 8(2):157-69. · 3.95 Impact Factor
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    ABSTRACT: Oncogenic osteomalacia is a rare clinicopathologic entity, linked to a mesenchymal tumor which overexpresses a hypophosphatemic factor, supposed to be the FGF-23. To date, about 100 cases have been published. We report the case of a 40-year-old man who presented an osteomalacic syndrome with no classical etiological diagnosis. The discovery of a subcutaneous tumor of the right foot and a high serum level of FGF-23 suggested the diagnosis of oncogenic osteomalacia. Surgical removal of the tumor resulted in complete reversal of the clinical and biochemical defects. Pathologic examination revealed spindle cells associated with osteoclast-like giant cells, embedded within a myxoid matrix which showed floculent calcification. These observations were compatible with the features of PMTMCT (Phosphaturic mesenchymal tumor mixed connective tissue variant).
    Annales de Pathologie 05/2005; 25(2):134-7. · 0.24 Impact Factor
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    ABSTRACT: Head and neck biopsies usually have a low diagnostic value in Wegener's granulomatosis (WG). On the basis of 49 biopsies obtained from 21 WG patients at diagnosis from various sites, i.e. nose (29), paranasal sinus (7), oral cavity (4), larynx (4), conjunctiva (3) and external ear (2), we described the suggestive histological features and studied the diagnostic potential of the biopsy size, anaesthesia method (general (GA) or local (LA)), anatomic region of the biopsy, number of sections, and presenting macroscopic manifestations. Associated granulomatous inflammation (scattered giant cells, 28.5% of biopsies; poorly-formed granulomas, 28.5%), necrosis (neutrophilic microabscesses, 16.3%; geographic necrosis, 18.3%), angiitis (leukocytoclastic, 10%; necrotizing, 12%; and granulomatous, 6%) which confirmed the diagnosis were only present in 18.3% of the biopsies (28.5% of the patients). We think it is possible to propose a "WG-compatible" diagnosis when at least one of these histological features is present (24.5% of biopsies, 26% of patients in our study). We found that it was always better to perform biopsies targeted on macroscopic lesions. When there was no lesion, samples from paranasal sinuses obtained under GA had the highest diagnostic value in the head and neck region, whereas 90% of nasal systematic biopsies performed under LA were nonspecific. Moreover, we demonstrated that performing two further sections increased the sensitivity of histological examination by 7%.
    Annales de Pathologie 05/2005; 25(2):87-93. · 0.24 Impact Factor
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    ABSTRACT: Oncogenic osteomalacia is a rare clinicopathologic entity, linked to a mesenchymal tumor which overexpresses a hypophosphatemic factor, supposed to be the FGF-23. To date, about 100 cases have been published. We report the case of a 40-year-old man who presented an osteomalacic syndrome with no classical etiological diagnosis. The discovery of a subcutaneous tumor of the right foot and a high serum level of FGF-23 suggested the diagnosis of oncogenic osteomalacia. Surgical removal of the tumor resulted in complete reversal of the clinical and biochemical defects. Pathologic examination revealed spindle cells associated with osteoclast-like giant cells, embedded within a myxoid matrix which showed floculent calcification. These observations were compatible with the features of PMTMCT (Phosphaturic mesenchymal tumor mixed connective tissue variant).
    Annales de Pathologie 01/2005; 25(2):134-137. · 0.24 Impact Factor
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    ABSTRACT: Head and neck biopsies usually have a low diagnostic value in Wegener's granulomatosis (WG). On the basis of 49 biopsies obtained from 21 WG patients at diagnosis from various sites, i.e. nose (29), paranasal sinus (7), oral cavity (4), larynx (4), conjunctiva (3) and external ear (2), we described the suggestive histological features and studied the diagnostic potential of the biopsy size, anaesthesia method (general (GA) or local (LA)), anatomic region of the biopsy, number of sections, and presenting macroscopic manifestations. Associated granulomatous inflammation (scattered giant cells, 28.5% of biopsies; poorly-formed granulomas, 28.5%), necrosis (neutrophilic microabscesses, 16.3%; geographic necrosis, 18.3%), angiitis (leukocytoclastic, 10%; necrotizing, 12%; and granulomatous, 6%) which confirmed the diagnosis were only present in 18.3% of the biopsies (28.5% of the patients). We think it is possible to propose a “WG-compatible” diagnosis when at least one of these histological features is present (24.5% of biopsies, 26% of patients in our study).We found that it was always better to perform biopsies targeted on macroscopic lesions. When there was no lesion, samples from paranasal sinuses obtained under GA had the highest diagnostic value in the head and neck region, whereas 90% of nasal systematic biopsies performed under LA were nonspecific. Moreover, we demonstrated that performing two further sections increased the sensitivity of histological examination by 7%.
    Annales de Pathologie 01/2005; 25(2):87-93. · 0.24 Impact Factor
  • Annales De Pathologie - ANN PATHOL. 01/2004; 24:150-150.
  • Annales De Pathologie - ANN PATHOL. 01/2004; 24:148-148.
  • Annales De Pathologie - ANN PATHOL. 01/2004; 24:142-142.
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    ABSTRACT: The DNA microarray technology enables the identification of the large number of genes involved in the complex deregulation of cell homeostasis taking place in cancer. Using Affymetrix microarrays, we have compared the gene expression profiles of highly purified malignant plasma cells from nine patients with multiple myeloma (MM) and eight myeloma cell lines to those of highly purified nonmalignant plasma cells (eight samples) obtained by in vitro differentiation of peripheral blood B cells. Two unsupervised clustering algorithms classified these 25 samples into two distinct clusters: a malignant plasma cell cluster and a normal plasma cell cluster. Two hundred and fifty genes were significantly up-regulated and 159 down-regulated in malignant plasma samples compared to normal plasma samples. For some of these genes, an overexpression or downregulation of the encoded protein was confirmed (cyclin D1, c-myc, BMI-1, cystatin c, SPARC, RB). Two genes overexpressed in myeloma cells (ABL and cystathionine beta synthase) code for enzymes that could be a therapeutic target with specific drugs. These data provide a new insight into the understanding of myeloma disease and prefigure that the development of DNA microarray could help to develop an 'à la carte' treatment in cancer disease.
    Oncogene 11/2002; 21(44):6848-57. · 7.36 Impact Factor
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    ABSTRACT: Les tumeurs primitives du système nerveux central (TPSNC) représentent un problème majeur de santé publique ; l’incidence serait d’environ 10 à 15 pour 100 000 habitants par an. Les facteurs étiologiques et pronostiques sont peu connus. Il n’existe pas de réel consensus concernant la classification histologique à utiliser Devant ces constatations nous avons souhaité réaliser une enquête nationale auprès des pathologistes et des neurochirurgiens pour connaître l’incidence de ces tumeurs en France sur 2000 et 2001. Nous avons obtenu un taux de réponse à cette enquête supérieur à 80 % avec une estimation de l’incidence des TPSNC en France de 13 cas/100 000 habitants/an. Ces résultats nous ont incités à proposer un projet d’enregistrement national, très bien accueilli par les neurochirurgiens et les anatomopathologistes. Une « fiche de recensement d’anatomopathologie en neurochirurgie » à remplir par le neurochirurgien et le pathologiste a été mise au point. L’ouverture du recensement s’est faite en septembre 2003 avec l’accord de la Société Française de Neuropathologie, la Société Française de Neurochirurgie, de l’Association des NeuroOncologues Français, et de l’InVS. Le Registre des Tumeurs de l’Hérault (disposant de l’expérience du recueil de données de la pathologie tumorale et des autorisations requises pour le respect de la confidentialité des données) s’est proposé de recueillir et d’enregistrer les données pendant une durée de 3 ans. Le nombre de fiches attendues pendant cette durée est de 6 500 pour les gliomes et de 13 000 pour les TPSNC. Au 1er mai (8 mois), 1 647 fiches ont été recensées par le Registre des Tumeurs de l’Hérault, sur 34 centres participants. Ce projet fait actuellement l’objet d’une demande de PHRC nationale. Nous nous proposons donc de présenter les premiers résultats, à un an de la mise en place de ce projet, et après réunion du groupe de travail regroupant les spécialistes impliqués dans le diagnostic et la prise en charge des TPSNC (anatomopathologiste, neurochirurgien, neurologue, radiologue, oncologue, radiothérapeute, soins palliatifs, épidémiologiste, fondamentaliste, généticien, etc.). Outre le recensement et l’enregistrement des nouveaux cas de TPSNC en France, ce projet vise également à étudier les pratiques anatomopathologiques, notamment en matière de classification histologique, ainsi que les principaux facteurs pronostiques cliniques et radiologiques des gliomes en France.
    Annales de Pathologie 24:133. · 0.24 Impact Factor
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