Frédérique Larousserie

Université René Descartes - Paris 5, Lutetia Parisorum, Île-de-France, France

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Publications (86)171.43 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Melanomas are aggressive skin tumors characterized by high metastatic potential. Our previous results indicate that Natural Killer (NK) cells may control growth of melanoma. The main defect of blood NK cells was a decreased expression of activating NCR1/NKp46 receptor and a positive correlation of NKp46 expression with disease outcome in stage IV melanoma patients was found. In addition, in stage III melanoma patients, we identified a new subset of mature NK cells in macro-metastatic Lymph nodes (LN). In the present studies, we evaluated the numbers of NK cells infiltrating primary cutaneous melanoma and analyzed immune cell subsets in a series of sentinel lymph nodes (SLN). First, we show that NKp46+ NK cells infiltrate primary cutaneous melanoma. Their numbers were related to age of patients and not to Breslow thickness. Then, a series of patients with tumor-negative or -positive sentinel lymph nodes matched for Breslow thickness of the cutaneous melanoma was constituted. We investigated the distribution of macrophages (CD68), endothelial cells, NK cells, granzyme B positive (GrzB+) cells and CD8+ T cells in the SLN. Negative SLN (SLN-) were characterized by frequent adipose involution and follicular hyperplasia compared to positive SLN (SLN+). High densities of macrophages and endothelial cells (CD34), prominent in SLN+, infiltrate SLN and may reflect a tumor favorable microenvironment. Few but similar numbers of NK and GrzB+ cells were found in SLN- and SLN+: NK cells and GrzB+ cells were not correlated. Numerous CD8+ T cells infiltrated SLN with a trend for higher numbers in SLN-. Moreover, CD8+ T cells and GrzB+ cells correlated in SLN- not in SLN+. We also observed that the numbers of CD8+ T cells negatively correlated with endothelial cells in SLN-. The numbers of NK, GrzB+ or CD8+ T cells had no significant impact on overall survival. However, we found that the 5 year-relapse rate was higher in SLN with higher numbers of NK cells.
    PLoS ONE 07/2015; 10(7):e0133363. DOI:10.1371/journal.pone.0133363 · 3.23 Impact Factor
  • P. Anract · F. Larousserie · A. Feydy · A. Babinet · D. Biau
  • The American journal of surgical pathology 04/2015; 39(7). DOI:10.1097/PAS.0000000000000461 · 5.15 Impact Factor
  • Revue de Chirurgie Orthopédique et Traumatologique 11/2014; 100(7):S253. DOI:10.1016/j.rcot.2014.09.104
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    ABSTRACT: Much discussion about benign notochordal cell tissue in vertebrae has centered on the nature of its relationship, if any, to chordoma. Often referred to as benign notochordal cell tumors (BNCTs), these lesions have unique morphological features, however, differentiating between notochordal cells in discs, BNCT, and chordoma can be difficult. They are described as radiologically distinct from chordoma, with lysis, contrast enhancement, and a soft tissue mass indicating chordoma. All chordomas diagnosed at our institution, the Istituto Ortopedico Rizzoli (Bologna, Italy), prior to 2008 were reviewed, yielding 174 cases. Five were limited to bone; one was a recurrent chordoma without original data available. The remaining four were re-evaluated in detail. There were three women and one man, aged 33-57 years (mean, 48 years). Two were BNCTs and two were mixed lesions containing BNCT and chordoma. On computed tomography, all were radiopaque with areas of lysis. One BNCT was heterogeneous on magnetic resonance imaging, enhancing after contrast. Microscopically, one BNCT had a well-defined cystic area with a sclerotic border. The other had a minute atypical area; it recurred as chordoma. The mixed lesions had areas of definitive BNCT, definitive chordoma, and atypical areas that did not meet the criteria for either. The atypical areas in all three cases 'blended' with areas of chordoma or BNCT. These cases illustrate the ongoing challenges in differentiating between BNCT and chordoma. All had unique imaging features; three had atypical microscopic areas blending with BNCT or chordoma, strengthening the argument for a relationship between the two entities and supporting the idea that some BNCTs may progress to chordoma. Our study dispels the notion that any single radiologic criterion used to distinguish between chordoma and BNCT is reliable, opening the discussion as to whether or how to monitor BNCTs.
    Cancer imaging : the official publication of the International Cancer Imaging Society 04/2014; 14(1):4. DOI:10.1186/1470-7330-14-4 · 2.07 Impact Factor
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    ABSTRACT: Extra-abdominal desmoid tumors are rare, locally aggressive neoplasms without metastatic potential. There is no clear consensus regarding their optimal management. The disappointing results of current treatments and the ability of extra-abdominal desmoid tumors to spontaneously stabilize have increasingly drawn interest toward conservative management. The objective of this study was to evaluate a wait-and-see policy as a first-line management for extra-abdominal desmoid tumors. This two-center retrospective study involved fifty-five patients with a histologically proven extra-abdominal desmoid tumor. The primary outcome was the cumulative probability of dropping out from the wait-and-see policy. The wait-and-see policy included aggressive management of symptoms. We conducted a review of the relevant published series in which a watchful-waiting strategy was used. The cumulative probability of dropping out from the wait-and-see policy was 9.6% at the time of the last follow-up. Spontaneous arrest of tumor growth was noted for forty-seven patients (85%) over the course of the study. Half of the tumors were stabilized at one year, and a potential to increase beyond three years was a sporadic event (one case). Regrowth was found in two patients (4%). A wait-and-see policy is an effective front-line management for patients with primary or recurrent extra-abdominal desmoid tumor. These tumors tend to stabilize spontaneously, on average after one year of evolution, and the cumulative probability of the failure of a wait-and-see policy is approximately 10%. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
    The Journal of Bone and Joint Surgery 04/2014; 96(8):631-8. DOI:10.2106/JBJS.M.00988 · 5.28 Impact Factor
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    ABSTRACT: Purpose Computerized tomography (CT) is routinely used for diagnosis of secondary chondrosarcomas arising on osteochondromas but its actual influence on the surgical treatment is unknown. We hypothesized that pre-operative CT helped to lower the incidence of death, local recurrence, and post-operative complications after surgical treatment of secondary chondrosarcomas. Methods We conducted a single center retrospective analysis on a cohort of patients treated before and after systematic utilization of pre-operative CT. We included 26 cases of secondary chondrosarcoma arising on osteochondromas (21 cases of multiple exostoses and 5 cases of a solitary exostosis) among 24 patients (10 females and 14 males, mean age of 34.5 years) at a mean follow-up of 12 years. Fourteen cases were operated on before and 12 after beginning systematic utilization of CT. We compared the two groups with a Student’s t test regarding the rates of death, recurrence, and post-operative complications. Results We reported a lower rate of death and recurrences in the group with pre-operative CT, but the differences were not statistically significant. Conclusion Despite the retrospective design and the low number of patients in this study, systematic pre-operative CT helped to improve the results of the surgical treatment of secondary chondrosarcomas arising on osteochondromas.
    03/2014; 6(1):45-50. DOI:10.1007/s12570-014-0284-9
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    ABSTRACT: Dedifferentiated liposarcoma (DDLPS) has been defined as a tumor composed of well-differentiated liposarcoma associated with a nonlipogenic undifferentiated sarcoma and is genetically characterized by a 12q13-15 amplicon with MDM2 amplification. Some peripheral (extremities, trunk wall, head/neck) undifferentiated pleomorphic sarcomas (UPS) without areas of well-differentiated liposarcoma present an MDM2 amplification. We addressed whether they are true DDLPS or not. We compared the clinical data, histologic data, MDM2 status (immunohistochemistry [IHC], fluorescence in situ hybridization [FISH]), genomic profile (array comparative genomic hybridization), and follow-up of 19 patients with peripheral UPS with MDM2 amplification and 62 with peripheral conventional DDLPS retrieved from the French sarcoma network (RRePS) and the Conticabase (Connective Tissue Cancer Network database). For a control cohort, we described 153 patients from the Conticabase, with peripheral UPS without expression of MDM2 by IHC. By IHC, tumor cells were positive for MDM2 in 59 conventional DDLPS and in all UPS with MDM2 amplification. FISH analysis and/or quantitative polymerase chain reaction showed amplification of MDM2 in 54 conventional DDLPS and in all UPS with MDM2 amplification. The 2-year overall survival rates of UPS with MDM2 amplification, conventional DDLPS, and UPS without expression of MDM2 were 93.3%, 90.7%, and 73.9%, respectively. Such similarities in the clinical characteristics, morphology, genomic profile, and follow-up of peripheral UPS with MDM2 amplification and peripheral conventional DDLPS strongly suggest that peripheral UPS with MDM2 amplification are in fact DDLPS. Faced with histologic diagnosis of UPS, a systematic IHC evaluation of MDM2 allows a selection of cases for FISH analysis permitting the diagnosis of DDLPS.
    The American journal of surgical pathology 03/2014; 38(3):293-304. DOI:10.1097/PAS.0000000000000131 · 5.15 Impact Factor
  • P. Anract · F. Larousserie · O. Mir · A. Feydy
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    ABSTRACT: Los condrosarcomas son tumores malignos primarios de estirpe condral. Se trata de un grupo heterogéneo de tumores que pueden caracterizarse por su localización en el hueso (central, o condrosarcoma convencional, o en la superficie del hueso, condrosarcoma propiamente dicho). Los tumores se distinguen por el aspecto histológico, además de la forma frecuente (donde existe diferenciación del tumor en cartílago hialino). Se observan condrosarcomas de células claras, desdiferenciados y mesenquimatosos. Además, se reconocen los formados a partir de una lesión cartilaginosa preexistente (osteocondroma o condroma), denominados «condrosarcomas secundarios». El condrosarcoma desarrollado sobre un osteocondroma también se conoce como «condrosarcoma periférico». Los condrosarcomas no son sensibles a la quimioterapia y son relativamente resistentes a la radioterapia. El tratamiento se basa en la resección quirúrgica. Estudios recientes de caracterización biológica permiten entrever posibilidades de tratamiento médico adyuvante.
    02/2014; 47(1):1–14. DOI:10.1016/S1286-935X(14)66938-0
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    ABSTRACT: The hallmark of neurofibromatosis type 1 (NF1) is the onset of dermal or plexiform neurofibromas, mainly composed of Schwann cells. Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors (MPNSTs) that are resistant to therapies. Experimental design: The aim of this study was to identify an additional pathway in the NF1-tumorigenesis. We focused our work on Wnt signalling that is highly implicated in cancer, mainly in regulating the proliferation of cancer stem cells. We quantified mRNAs of 89 Wnt pathway genes in 57 NF1-associated tumors including dermal and plexiform neurofibromas and MPNSTs. Expression of two major stem cell marker genes and five major epithelial-mesenchymal transition marker genes was also assessed. The expression of significantly deregulated Wnt genes was then studied in normal human Schwann cells, fibroblasts, endothelial cells, and mast cells and in seven MPNST cell lines. The expression of nine Wnt genes was significantly deregulated in plexiform neurofibromas in comparison with dermal neurofibromas. Twenty Wnt genes showed altered expression in MPNST biopsies and cell lines. Immunohistochemical studies confirmed the Wnt pathway activation in NF1-associated MPNSTs. We then confirmed that the knock-down of NF1 in Schwann cells but not in epithelial cells provoked the activation of Wnt pathway by functional transfection assays. Furthermore, we showed that the protein expression of active beta-catenin was increased in NF1-silenced cell lines. Wnt pathway activation was strongly associated to both cancer stem cell reservoir and Schwann-mesenchymal transition. We highlighted the implication of Wnt pathway in NF1-associated tumorigenesis.
    Clinical Cancer Research 11/2013; 20(2). DOI:10.1158/1078-0432.CCR-13-0780 · 8.72 Impact Factor
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    ABSTRACT: [This corrects the article on p. e75694 in vol. 8.].
    PLoS ONE 11/2013; 8(11). DOI:10.1371/annotation/e1a0e85e-e632-40f2-9925-e0b71eb18b56 · 3.23 Impact Factor
  • Frédérique Larousserie · Catherine Genestie
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    ABSTRACT: The histologic diagnosis of bone metastasis is often easy, based on tumor morphologic features on routine examination. The determination of the primary tumor is facilitated by ancillary techniques such as histochemical stainings and immunohistochemistry: it is possible, in about 65% of cases, with clinical correlation. Additional immunohistochemistry or molecular analyses are becoming more useful in various tumors (breast, lung, melanoma…) to give targeted therapy. From a technical point of view, bone is characterised by its difficulty to be sampled (with frequent crushing artifacts) and the necessity to decalcify samples with increase time of technique and frequent loss of nuclear markers antigenicity and difficulties in molecular analyses.
    Bulletin du cancer 11/2013; 100(11). DOI:10.1684/bdc.2013.1844 · 0.60 Impact Factor
  • D. Vanel · F. Larousserie
    11/2013; 94(11):1180. DOI:10.1016/j.jradio.2013.10.002
  • D Vanel · F Larousserie
    Diagnostic and interventional imaging 11/2013; 94(11):1181. DOI:10.1016/j.diii.2013.10.008
  • Nicolas Pinar · Julien Even · Frédérique Larousserie · Antoine Babinet · David Biau · Philippe Anract
    Revue de Chirurgie Orthopédique et Traumatologique 11/2013; 99(7):S347. DOI:10.1016/j.rcot.2013.09.195
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    ABSTRACT: Interleukin (IL)-27 is a cytokine of the IL-12 family that displays either immunostimulatory or immunosuppressive functions depending on the context. In various murine tumor models including melanoma models, ectopic expression of IL-27 has been shown to play an anti-tumoral role and to favor tumor regression. In this study, we investigated whether IL-27 might play a role in the development of melanoma in humans. We analyzed the in situ expression of IL-27 in melanocytic lesions (n = 82) representative of different stages of tumor progression. IL-27 expression was not observed in nevus (n = 8) nor in in situ melanoma (n = 9), but was detected in 28/46 (61%) cases of invasive cutaneous melanoma, notably in advanced stages (19/23 cases of stages 3 and 4). In most cases, the main source of IL-27 was tumor cells. Of note, when IL-27 was detected in primary cutaneous melanomas, its expression was maintained in metastatic lesions. These in situ data suggested that the immunosuppressive functions of IL-27 may dominate in human melanoma. Consistent with this hypothesis, we found that IL-27 could induce suppressive molecules such as PD-L1, and to a lesser extent IL-10, in melanoma cells, and that the in situ expression of IL-27 in melanoma correlated with those of PD-L1 and IL-10.
    PLoS ONE 10/2013; 8(10):e75694. DOI:10.1371/journal.pone.0075694 · 3.23 Impact Factor
  • Frédérique Larousserie
    Annales de Pathologie 08/2013; 33(4):255-8. DOI:10.1016/j.annpat.2013.06.001 · 0.29 Impact Factor
  • G. Riouallon · F. Larousserie · E. Pluot · P. Anract
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    ABSTRACT: Introduction Les myxofibrosarcomes superficiels sont des tumeurs conjonctives malignes, dont les récidives, extrêmement fréquentes, mettent en jeu le pronostic local et général. Même lorsque l’exérèse chirurgicale semble complète macroscopiquement, elle est très souvent microscopiquement contaminée. Le but de ce travail était d’évaluer la récidive en fonction des marges de résection et de comparer, quand cela était possible, la taille de la lésion évaluée cliniquement et macroscopiquement par l’anatomopathologiste. Patients et méthodes Il s’agit d’une série rétrospective monocentrique composée de 21 patients, d’un âge moyen de 67 ans, pris en charge pour un myxofibrosarcome superficiel. Le nombre, la date et la localisation des récidives ont été colligés pour chaque patient. Pour chaque récidive, le plus grand axe de la tumeur a été évalué cliniquement et à l’examen anatomopathologique. Résultats Cinquante-sept pour cent des patients ont présenté une récidive. Le nombre moyen de récidives était de 1,4 par patient (1 à 8). Les marges de résection étaient saines dans quatre cas, marginales dans deux cas et incomplètes pour les 15 autres patients avec des taux de récidives respectifs de 25, 50 et 67 %. La taille évaluée à l’examen clinique préopératoire (14 cas) était sous-estimée en moyenne de 2,4 cm par rapport à la taille évaluée par l’examen macroscopique anatomopathologique. La taille évaluée sur l’IRM préopératoire (5 cas) était également sous-estimée de 1,3 cm en moyenne. Conclusion Les myxofibrosarcomes superficiels sont des tumeurs difficiles à réséquer complètement d’emblée en raison de leur caractère infiltrant, souvent sous-estimé avant l’intervention. Leur traitement chirurgical nécessite des marges de résection beaucoup plus larges que ne le laissent prévoir l’évaluation clinique et l’IRM. En cas de résection incomplète, la reprise cicatricielle doit être faite systématiquement. Niveau de preuve IV. Étude rétrospective.
    Revue de Chirurgie Orthopédique et Traumatologique 06/2013; 99(4):390–395. DOI:10.1016/j.rcot.2012.12.008
  • G Riouallon · F Larousserie · E Pluot · P Anract
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    ABSTRACT: INTRODUCTION: Superficial myxofibrosarcomas are malignant connective tissue tumors, whose very frequent recurrence influences the local and vital prognosis. Even when resection seems to be macroscopically complete it is very often microscopically contaminated. The aim of this study was to evaluate recurrence in relation to the surgical margins and to compare, when possible, tumor size, evaluated clinically and macroscopically by the pathologist. MATERIALS AND METHODS: This was a single center study of 21 patients, mean age 67 years old, treated for superficial myxofibrosarcoma. The number, date and location of recurrence were collected for each patient. A clinical and pathological measurement was made of the longest axis of the tumor in each case of recurrence. RESULTS: Fifty-seven percent of patients presented with recurrent tumors. The mean number of recurrences was 1.4 per patient (1-8). The surgical margins were wide in four cases, marginal in two cases and incomplete/intralesional in 15 other patients with a rate of recurrence of 25, 50 and 67% respectively. The size evaluated during the preoperative clinical examination (14 cases) was underestimated by a mean 2.4cm compared to the macroscopic pathology assessment. The preoperative size on MRI (5 cases) was also underestimated by a mean 1.3cm. CONCLUSION: Superficial myxofibrosarcomas are tumors that are difficult to resect completely because they are infiltrative, a feature that is often underestimated before surgery. Surgical treatment of this entity requires a much larger surgical margin than that suggested by the preoperative clinical and MRI evaluations. In case of incomplete resection, revision scar surgery should systematically be performed. LEVEL OF EVIDENCE: Level IV. Retrospective study.
    Orthopaedics & Traumatology Surgery & Research 04/2013; 99(4). DOI:10.1016/j.otsr.2012.11.020 · 1.26 Impact Factor
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    ABSTRACT: GNAS (guanine nucleotide-binding protein/α-subunit) mutations that induce the activation of G-protein α-subunit participate in the pathogenesis of fibrous dysplasia. The aim of this study was to evaluate the sensitivity and specificity of GNAS mutations in fibrous dysplasia and other fibro-osseous lesions, to assess the value of investigating this mutation in the diagnosis of fibro-osseous lesions. We studied 91 cases of fibrous dysplasia. The quality and/or quantity of genomic DNA were suitable for molecular analysis for 51 cases of fibrous dysplasia. GNAS mutations were investigated by three techniques: high-resolution melting (exon 8), allele-specific PCR (exons 8 and 9) and/or direct DNA sequencing (exons 8 and 9). Fibrous dysplasia samples were classified blind to the GNAS mutation status into six histological subtypes as conventional, fibro-involutive, osteosclerosing, cementifying, osteocartilaginous and with prominent aneurysmal cystic changes. We also studied 14 cases of low-grade osteosarcoma, 21 cases of ossifying fibroma, 3 cases of osteofibrous dysplasia, 1 case of osseous dysplasia of the jawbone and 1 post-traumatic lesion of the ribs. Twenty-three cases of fibrous dysplasia (45%) showed mutations of codon 201 (exon 8, p.R201H or p.R201C). No mutation was found on codon 227 (exon 9). GNAS mutations in conventional fibrous dysplasia were detected in the same proportion (47%) as in the other histological subtypes (47%, P=0.96), regardless of sex (P=0.44), age (P=0.90) and location (P=1). GNAS mutations were not detected in any other fibro-osseous lesions. The GNAS mutation was thus specific to fibrous dysplasia in the context of fibro-osseous lesions. The particular mosaicism of mutant and non-mutant cells within the lesion or the existence of other mutations not already described could explain the lack of GNAS mutation in cases of fibrous dysplasia. Investigating this mutation may constitute a valuable complementary diagnostic tool, despite its low sensitivity, particularly in unconventional morphologically different subtypes of fibrous dysplasia.
    Modern Pathology 02/2013; 26(7). DOI:10.1038/modpathol.2012.223 · 6.19 Impact Factor

Publication Stats

671 Citations
171.43 Total Impact Points


  • 2009–2014
    • Université René Descartes - Paris 5
      • • Faculty of medicine
      • • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Istituto Ortopedico Rizzoli
      Bolonia, Emilia-Romagna, Italy
  • 2011
    • Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 2010
    • CHRU de Strasbourg
      Strasburg, Alsace, France
  • 2006–2009
    • Hôpital Européen Georges-Pompidou (Hôpitaux Universitaires Paris-Ouest)
      • Service de Chirurgie Cancérologique Gynécologique et du Sein
      Paris, Ile-de-France, France
  • 2008
    • Hôpital Paris Saint Joseph
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2005–2007
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France