Johannes Bras

Academisch Medisch Centrum Universiteit van Amsterdam, Amsterdam, North Holland, Netherlands

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Publications (32)84.57 Total impact

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    ABSTRACT: Epithelioid sarcoma is a rare but often aggressive malignancy of soft tissue that usually occurs in young adults as a superficial lesion in the distal upper limbs. To date, there are only 4 case reports of epithelioid sarcoma primarily occurring in the orbit. Two of these patients were treated with primary exenteration only one of whom was alive 3 years after diagnosis. Radical surgical excision is thus the first treatment of choice for primary orbital epithelioid sarcoma. The authors present a patient with primary orbital epithelioid sarcoma who refused exenteration. Surgical debulking followed by local brachytherapy was performed. The patient remains tumor free 5 years after diagnosis. The literature remains limited regarding treatment options for primary orbital epithelioid sarcoma. However, based on reported cases and this case, the authors conclude that surgical excision combined with local iridium radiation therapy is an acceptable treatment when treating primary orbital epithelioid sarcoma.
    Ophthalmic plastic and reconstructive surgery. 07/2014;
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    ABSTRACT: Epithelioid hemangioendothelioma is a malignant, often indolent vascular tumor which occurs at various anatomic sites. Based on a reciprocal translocation t (1;3) (p36;q25), a consistent WWTR1-CAMTA1 fusion gene has been found. An alternate YAP1-TFE3 fusion has been detected in a small and distinct subset of cases.
    Diagnostic pathology. 07/2014; 9(1):131.
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    ABSTRACT: AIMS: Chondroid lipomas are benign adipose tissue tumours. Their rarity and peculiar morphology can lead to misinterpretation, especially in small biopsies. Based on a recurrent translocation t(11;16)(q13;p13), the C11orf95-MKL2 fusion gene has been found in a few cases. Therefore, it seemed appropriate to look for this fusion gene in a larger cohort. METHODS AND RESULTS: We describe eight further cases from four females and four males with an age range of 21-81 years (median 49 years). The tumours were situated in the lower arm (three), lower leg (two), thigh (one), back (one) and head (one); seven lesions were deep-seated and one was located subcutaneously. Sizes ranged from 3 to 12 cm (median 6.3 cm). All patients were treated by simple excision, and follow-up, available for six patients (range 2 months-12 years; median 15 months), demonstrated recurrence in one case. Histologically, the circumscribed and lobulated tumours showed a variable composition of adipocytes, lipoblasts, hibernoma-like cells and chondroblast-like cells embedded in a chondroid matrix. Immunohistochemistry, performed in four cases, revealed positivity for S-100 and pancytokeratin in two of three neoplasms stained for each marker. A C11orf95-MKL2 fusion gene was shown by RT-PCR analysis in seven of the eight cases. CONCLUSIONS: Molecular analysis can be used to support the diagnosis of chondroid lipoma, especially in small samples. This may be helpful in planning treatment when the differential diagnosis includes malignant lesions.
    Histopathology 05/2013; 62(6):925-930. · 2.86 Impact Factor
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    ABSTRACT: The Ablative surgery, MOulage brachytherapy and REconstruction) (AMORE) protocol developed in the Academic Medical Center of Amsterdam has been used successfully to treat sarcomas. The use of endoscopic surgery fits well within this framework. A 6-year-old boy presented with Ewing Sarcoma of left ethmoid sinus closest to orbit. The patient underwent neoadjuvant chemotherapy followed by complete endoscopic resection, brachytherapy and reconstruction. Brachytherapy was administered by iridium catheters through limited Lynch-Howarth incision. Skull base defect was reconstructed with a galea flap. The use of endoscopic surgery complemented by neoadjuvant chemotherapy and brachytherapy might maximize tumor control while reducing morbidity.
    International journal of pediatric otorhinolaryngology 10/2012; · 0.85 Impact Factor
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    ABSTRACT: Conventional imaging modalities are unable to depict the early degeneration of articular cartilage in osteoarthritis, especially in small joints. Optical coherence tomography has previously been used successfully in high-resolution imaging of cartilage tissue. This pilot cadaver study demonstrates the use of intra-articular optical coherence tomography in imaging of articular cartilage of the first carpometacarpal joint, producing high resolution images of the articular surface in which cartilage thickness and surface characteristics were assessed. Findings on optical coherence tomography were confirmed with histology. Furthermore, co-registration of optical coherence tomography and computed tomography was used to accurately determine the scanned trajectory and reconstruct a true-scale image overlay.
    Journal of Biomedical Optics 06/2012; 17(6):060501. · 2.88 Impact Factor
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    ABSTRACT: PTEN: hamartoma tumor syndrome (PHTS) is a group of syndromes caused by mutations in PTEN. Gorham-Stout phenomenon (GSP) is a rare condition characterized by proliferation of vascular structures in bones, resulting in progressive osteolysis. Here we present a 1-year-old boy with PHTS and GSP. The lesion that later proved to be GSP was evident from the age of 4 months, and became symptomatic at the age of 1 year. Eventually, he developed a fatal chylothorax. Mutation analysis revealed a germline heterozygous mutation c.517 C>T (p.Arg173Cys) in exon 6 of PTEN. Analysis of the lymphatic malformation (LM) tissue revealed no loss of heterozygosity (LOH) nor a second, somatic PTEN mutation of the remaining wild type allele. The germline p.Arg173Cys mutation was also present in the mother and the propositus' younger sister and brother. Further molecular work-up showed a heterozygous variant c.2180C>T (p.Ala727Val) FLT4 in the LM tissue, which was also present in the germline of mother and two siblings. GSP has not been reported before in a patient with a PTEN mutation. Up to this date, this mutation is the only genetic defect possibly involved in the etiology of GSP which is plausible given the known function of PTEN in angiogenic signaling.
    American Journal of Medical Genetics Part A 05/2012; 158A(7):1719-23. · 2.30 Impact Factor
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    ABSTRACT: In neuroblastoma (NB) patients, minimal residual disease (MRD) can be detected by real-time quantitative PCR (qPCR) using NB-specific target genes, such as PHOX2B and TH. However, it is unknown whether the mRNA levels of these targets vary either during treatment or at relapse. If marker genes are not stably expressed, estimation of MRD levels in bone marrow (BM) or peripheral blood will be hampered. We studied the stability of a panel of qPCR markers in primary tumors at diagnosis compared with i) paired metastasis (n = 7), ii) treated (n = 10), and iii) relapse (n = 6) tumors. We also compared relative expression of the targets in iv) primary tumors and BM at diagnosis (n = 17), v) BM and peripheral blood at diagnosis (n = 20), vi) BM at diagnosis and during treatment (n = 26), and vii) BM from different puncture sides (n = 110). Especially at diagnosis, PCR target expression is quite stable. Accurate quantification is possible when expression level can be related to the primary tumor; however, PCR target expression can alter on treatment and at relapse. If the median value of relative expression of a panel of PCR targets is used, most variations due to treatment and outgrowth of subclones level out, allowing for reliable application and quantification of MRD-PCR targets in NB patients.
    The Journal of molecular diagnostics: JMD 03/2012; 14(2):168-75. · 3.48 Impact Factor
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    JBR-BTR: organe de la Société royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie (KBVR) 01/2012; 95(3):172-3.
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    ABSTRACT: Osteosarcoma is the most common primary malignancy of bone. The tumours are characterized by high genomic instability, including the occurrence of multiple regions of amplifications and deletions. Chromosome region 17p11.2-p12 is amplified in about 25% of cases. In previous studies, COPS3 and PMP22 have been identified as candidate oncogenes in this region. Considering the complexity and variation of the amplification profiles for this segment, the involvement of additional causative oncogenes is to be expected. The aim of the present investigation is to identify novel candidate oncogenes in 17p11.2-p12. We selected 26 of in total 85 osteosarcoma samples (31%) with amplification events in 17p11.2-p12, using quantitative PCR for 8 marker genes. These were subjected to high-resolution SNP array analysis and subsequent GISTIC analysis to identify the most significantly amplified regions. Two major amplification peaks were found in the 17p11.2-p12 region. Overexpression as a consequence of gene amplification is a major mechanism for oncogene activation in tumours. Therefore, to identify the causative oncogenes, we next determined expression levels of all genes within the two segments using expression array data that could be generated for 20 of the selected samples. We identified 11 genes that were overexpressed through amplification in at least 50% of cases. Nine of these, c17orf39, RICH2, c17orf45, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1, demonstrated a significant association between copy number and expression level. We conclude that these genes, including COPS3 and PMP22, are candidate oncogenes in 17p11.2-p12 of importance in osteosarcoma tumourigenesis.
    PLoS ONE 01/2012; 7(1):e30907. · 3.73 Impact Factor
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    ABSTRACT: To enhance the efficacy of fenretinide (4HPR)-induced reactive oxygen species (ROS) in neuroblastoma, 4HPR was combined with buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, in neuroblastoma cell lines and spheroids, the latter being a three-dimensional tumor model. 4HPR exposure (2.5-10 μM, 24 h) resulted in ROS induction (114-633%) and increased GSH levels (68-120%). A GSH depletion of 80% of basal levels was observed in the presence of BSO (25-100 μM, 24 h). The 4HPR-BSO combination resulted in slightly increased ROS levels (1.1- to 1.3-fold) accompanied by an increase in cytotoxicity (110-150%) compared to 4HPR treatment alone. A correlation was observed between the ROS-inducing capacity of each cell line and the increase in cytotoxicity induced by 4HPR-BSO compared to 4HPR. No significant correlation between baseline antioxidant levels and sensitivity to 4HPR or BSO was observed. In spheroids, 4HPR-BSO induced a strong synergistic growth retardation and induction of apoptosis. Our data show that BSO increased the cytotoxic effects of 4HPR in neuroblastoma monolayers and spheroids in ROS-producing cell lines. This indicates that the 4HPR-BSO combination might be a promising new strategy in the treatment of neuroblastoma.
    Free Radical Biology & Medicine 09/2011; 51(6):1213-20. · 5.27 Impact Factor
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    ABSTRACT: Aims. Chondroid lipoma (CL) is a benign tumor that mimics a variety of soft tissue tumors and is characterized by translocation t(11;16). Here, we analyze CL and its histological mimics. Methods. CL (n = 4) was compared to a variety of histological mimics (n = 83) for morphological aspects and immunohistochemical features including cyclinD1(CCND1). Using FISH analysis, CCND1 and FUS were investigated as potential translocation partners. Results. All CLs were strongly positive for CCND1. One of 4 myoepitheliomas, CCND1, was positive. In well-differentiated lipomatous tumors and in chondrosarcomas, CCND1 was frequently expressed, but all myxoid liposarcomas were negative. FISH analysis did not give support for direct involvement of CCND1 and FUS as translocation partners. Conclusions. Chondroid lipoma is extremely rare and has several and more prevalent histological mimics. The differential diagnosis of chondroid lipomas can be unraveled using immunohistochemical and molecular support.
    Sarcoma 01/2011; 2011:638403.
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    ABSTRACT: Wilms tumor is the most common pediatric renal neoplasm, but few molecular prognostic markers have been identified for this tumor. Somatic deletion in the long arm of chromosome 16 (16q) is known to predict a less favorable outcome in Wilms tumor, but the underlying molecular mechanisms are not known. We show that 16q deletions are typically confined to immature anaplastic-blastic tumor elements, while deletions are absent in maturing tumor components. The smallest region of deletion overlap mapped to a 1.8-Mb segment containing the IRXB gene cluster including IRX3, IRX5, and IRX6, of which IRX3 is a recently identified regulator of tubular maturation during nephrogenesis. Tumors with 16q deletion showed a lower overall mRNA expression of IRXB genes, and 16q-deleted tumor cells failed to express IRX3 while it was expressed in differentiating tubular tumor elements with intact 16q. Consistent with a role for IRX3 in tubular differentiation, gene sets linked to Notch signaling, Rho signaling, and ion channel activity were enriched in tumors with high IRX3 expression, while WTs with low expression were enriched for gene sets linked to cell cycle progression. Low mRNA levels of IRXB genes were associated with diffuse anaplasia, high-stage disease, and death. A disturbed balance between tubular differentiation and self-renewal of anaplastic-blastic elements may thus be one mechanism linking 16q deletion to adverse outcome in Wilms tumor.
    American Journal Of Pathology 11/2010; 177(5):2609-21. · 4.52 Impact Factor
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    ABSTRACT: Rhabdomyosarcoma (RMS) is the commonest paediatric soft-tissue sarcoma constituting 3-5% of all malignancies in childhood. RMS has a predilection for the head and neck area and tumours in this location account for 40% of all childhood RMS cases. In this review we address the clinical and imaging presentations of craniofacial RMS, discuss the most appropriate imaging techniques, present characteristic imaging features and offer an overview of differential diagnostic considerations. Post-treatment changes will be briefly addressed.
    Pediatric Radiology 11/2010; 40(11):1723-38; quiz 1855. · 1.57 Impact Factor
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    Ped Radiol. 01/2010; 40(11):1723-1738.
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    ABSTRACT: This report describes the radiological and histological findings of a small cell osteosarcoma of a toe phalanx in a 38 year old man. This man presented with pain, swelling and redness of the left third toe. Medical history revealed an osteomyelitis of this toe eight years prior. Based on clinical findings and medical history the lesion was diagnosed as an osteomyelitis. However, peroperatively the lesion had a malignant aspect. Histological examination revealed a small cell osteosarcoma of the proximal phalanx.Osteosarcoma of the foot and especially of the tubular bones is rare. Moreover small cell osteosarcoma is a rare subtype of osteosarcoma. This case demonstrates that medical history and clinical examination can be misleading. In patients with apparent bone destruction, a malignancy must always be excluded prior to treatment. It emphasises the care that should be taken in the process of formulating a diagnosis.
    Journal of Orthopaedic Surgery and Research 01/2010; 5:36. · 1.01 Impact Factor
  • Cancer Genetics and Cytogenetics - CANCER GENET CYTOGENET. 01/2010; 203(1):76-76.
  • Pediatric Blood & Cancer 07/2009; 53(4):683-4. · 2.35 Impact Factor
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    ABSTRACT: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood. This paper is focuses on imaging for diagnosis, staging, and follow-up of noncraniofacial RMS.
    Pediatric Radiology 07/2008; 38(6):617-34. · 1.57 Impact Factor
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    ABSTRACT: The efficacy and mechanism of action of fenretinide (4-HPR), a vitamin A analogue, was investigated in a panel of six neuroblastoma cell lines and multicellular tumor spheroids. The latter are three dimensional cell aggregates and as such, a model for micrometastases. In all cell lines, the production of reactive oxygen species (ROS) increased with 163-680% after 1 h of treatment with 4-HPR. In addition, a decrease of the mitochondrial membrane potential of 30-75% was observed after 4 h of incubation with 4-HPR. A 6-12-fold difference was observed between the IC50 values for cell proliferation and viability between the most sensitive (IMR32) and most resistant (NASS) cell line towards 4-HPR. Flow cytometric analysis showed an increased amount of apoptotic bodies and no cell-cycle arrest. The antioxidant Trolox completely inhibited the accumulation of 4HPR-induced ROS and prevented the 4HPR-associated cytotoxicity. In all neuroblastoma spheroids, 4-HPR induced a complete cytostasis at clinical relevant concentrations (3-10 microM). Immunohistochemical analysis of 4-HPR-treated spheroids showed a decreased staining for proliferation marker Ki-67 and an increased staining for cleaved-PARP, a marker of apoptosis. Our results suggest that 4-HPR might be a promising agent for the treatment of micrometastases and high-risk neuroblastoma.
    International Journal of Oncology 06/2008; 32(5):1011-9. · 2.66 Impact Factor
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    ABSTRACT: Neuroblastoma and ganglioneuroma are neuroblastic tumors originating from the developing sympathetic peripheral nervous system. Ganglioneuromas are usually benign, while neuroblastomas have a variable prognosis and include very aggressive tumors. Examples exist of neuroblastomas regressing to ganglioneuromas and ganglioneuromas progressing to neuroblastomas. Little is known of the molecular differences between the tumor types. Here we report that Dickkopf-3 (DKK3), a putative extra cellular inhibitor of the Wnt/beta-catenin pathway, showed a strongly differential expression between neuroblastoma and ganglioneuroma. Microarray analyses of 109 neuroblastic tumors revealed that DKK3 is strongly expressed in ganglioneuroma but only weakly in neuroblastoma. Low DKK3 expression in neuroblastoma correlated with a poor prognosis. The expression of DKK3 in the tumor series and in neuroblastoma cell lines was inversely correlated with the expression of the MYCN oncogene. Analysis of 2 neuroblastoma cell lines with inducible activity of MYCN showed that DKK3 is down-regulated by MYCN. We subsequently generated cell lines with inducible expression of DKK3, which revealed an inhibitory effect of DKK3 on proliferation. High DKK3 expression in the benign ganglioneuromas and down-regulation of DKK3 by MYCN in neuroblastoma might contribute to the strongly different clinical behavior of both neuroblastic tumor types.
    International Journal of Cancer 05/2008; 122(7):1455-64. · 6.20 Impact Factor

Publication Stats

228 Citations
84.57 Total Impact Points

Institutions

  • 2002–2011
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Pathology
      Amsterdam, North Holland, Netherlands
  • 2010
    • University of Amsterdam
      • Department of Pathology
      Amsterdamo, North Holland, Netherlands
  • 2007–2010
    • Lund University
      • Department of Clinical Genetics
      Lund, Skane, Sweden