RESUMEN
BACKGROUND: Ovarian mature teratoma (OMT) is a common ovarian tumor found in the pediatric population. In 10%-20% of cases, OMT occurs as multiple synchronous or metachronous lesions on ipsi- or contralateral ovaries. Ovarian-sparing surgery (OSS) is recommended to preserve fertility, but total oophorectomy (TO) is still performed. DESIGN: This study reviews the clinical data of patients with OMT, and analyzes risk factors for second events. A national retrospective review of girls under 18 years of age with OMTs was performed. Data on clinical features, imaging, laboratory studies, surgical reports, second events and their management were retrieved. RESULTS: Overall, 350 children were included. Eighteen patients (5%) presented with a synchronous bilateral form at diagnosis. Surgery was performed by laparotomy (85%) and laparoscopy (15%). OSS and TO were performed in 59% and 41% of cases, respectively. Perioperative tumor rupture occurred in 23 cases, independently of the surgical approach. Twenty-nine second events occurred (8.3%) in a median time of 30.5 months from diagnosis (ipsilateral: eight cases including one malignant tumor; contralateral: 18 cases; both ovaries: three cases). A large palpable mass, bilateral forms, at diagnosis and perioperative rupture had a statistical impact on the risk of second event, whereas the type of surgery or approach did not. CONCLUSION: This study is a plea in favor of OSS as the first-choice treatment of OMT when possible. Close follow-up during the first 5 years is mandatory considering the risk of 8.3% of second events, especially in cases with risk factors.
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Neoplasias Ováricas , Teratoma , Adolescente , Niño , Femenino , Humanos , Neoplasias Ováricas/patología , Ovariectomía , Estudios Retrospectivos , Teratoma/patologíaRESUMEN
Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare lesions of the central nervous system. To date, about 60 cases have been reported in literature. We present a case that had the peculiarity to occur in a pregnant woman. At 32 weeks of gestation, a 26-year-old woman was hospitalized to explore nocturnal epigastralgia. During the hospitalisation, the patient presented generalised seizures. As an eclampsia had been suspected, a caesarean delivery was performed. Post-operatively, the patient harboured memory disorders and neuro-imaging explorations were done. They showed an intracerebral calcified mass located in the left frontal lobe and surrounded by an oedema. A complete surgical resection was performed. Histological examination of the surgical specimen showed a calcified tissue containing a fibrillary or granular material. A dense and hyalinised eosinophilic material focally surrounded the calcifications and contained regular fusiform cells of fibroblastic type. Foci of lipomatous and osseous metaplasia were present. Immunohistochemical staining for EMA and STAT6 was negative. There was no associated meningioangiomatosis nor tumour proliferation. Forty-five months after surgery, the patient did not present any seizures and had no sequelae. CAPNON are rare lesions occurring at any age. Their location in the central nervous system is ubiquitous and they can be intra or extra axial. The treatment is surgical and the prognosis excellent. CAPNON must be recognized and distinguished from the other calcified lesions, tumoural or non-tumoural, to avoid an inadequate and potentially harmful treatment.
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Edema Encefálico/patología , Calcinosis/patología , Lóbulo Frontal/patología , Complicaciones del Embarazo/patología , Adulto , Edema Encefálico/complicaciones , Edema Encefálico/diagnóstico , Edema Encefálico/cirugía , Neoplasias Encefálicas/diagnóstico , Calcinosis/diagnóstico , Calcinosis/diagnóstico por imagen , Calcinosis/cirugía , Cesárea , Diagnóstico Diferencial , Eclampsia/diagnóstico , Epilepsia Generalizada/etiología , Epilepsia Generalizada/patología , Femenino , Lóbulo Frontal/cirugía , Humanos , Imagen por Resonancia Magnética , Neuroimagen , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/diagnóstico por imagen , Complicaciones del Embarazo/cirugíaRESUMEN
INTRODUCTION: Fibroepithelial polyps (FEP) of the lower urinary tract are relatively common in adults but rare in children, with fewer than 250 cases reported in the literature to date. OBJECTIVE: The aim of this study was to address the experience of FEP management in children. STUDY DESIGN: A retrospective multicenter review was undertaken in children with defined FEP of the lower urinary tract managed between 2008 and 2018. The data at 18 pediatric surgery centers were collected. Their demographic, radiological, surgical, and pathological information were reviewed. RESULTS: A total of 33 children (26 boys; 7 girls) were treated for FEP of the lower urinary tract at 13 centers. The most common presentation was urinary outflow as hematuria (41%), acute urinary retention (25%), dysuria (19%), or urinary infections (28%). A prenatal diagnosis was made for three patients with hydronephrosis. Almost all of the children (94%) underwent ultrasound imaging of the urinary tract as the first diagnostic examination, 23 (70%) of them also either had an MRI (15%), cystourethrography (25%), computerized tomography (6%), or cystoscopy (45%). Two of these children (6%) had a biopsy prior to the surgery. The median preoperative delay was 7.52 (range: 1-48) months. Most of the patients were treated endoscopically, although four (12.1%) had open surgery and two (6.1%) had an additional incision for specimen extraction. The median hospital stay was 1.5 (range: 1-10) days. There were no recurrences and no complications after a median follow-up of 13 (range: 1-34) months. DISCUSSION: The main limitation of our study is the retrospective design, although it is the largest one for this pathology. CONCLUSION: This series supports sonography as the most suitable diagnosis tool before endoscopy to confirm the diagnosis and to perform the resection for most FEP in children. This report confirms the recognized benign nature in the absence of recurrences. LEVEL OF EVIDENCE: Level V.
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Pólipos , Sistema Urinario , Adulto , Niño , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia , Pólipos/diagnóstico por imagen , Pólipos/cirugía , Estudios Retrospectivos , Vejiga UrinariaRESUMEN
BACKGROUND: Since 2010, nationwide networks of reference centers for sarcomas (RREPS/NETSARC/RESOS) collected and prospectively reviewed all cases of sarcomas and connective tumors of intermediate malignancy (TIM) in France. METHODS: The nationwide incidence of sarcoma or TIM (2013-2016) was measured using the 2013 WHO classification and confirmed by a second independent review by expert pathologists. Simple clinical characteristics, yearly variations and correlation of incidence with published clinical trials are presented and analyzed. RESULTS: Over 150 different histological subtypes are reported from the 25172 patients with sarcomas (n = 18712, 74,3%) or TIM (n = 6460, 25.7%), with n = 5838, n = 6153, n = 6654, and n = 6527 yearly cases from 2013 to 2016. Over these 4 years, the yearly incidence of sarcomas and TIM was therefore 70.7 and 24.4 respectively, with a combined incidence of 95.1/106/year, higher than previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of tumors. Only GIST, as a single entity had a yearly incidence above 10/106/year. There were respectively 30, 64 and 66 different histological subtypes of sarcomas or TIM with an incidence ranging from 10 to 1/106, 1-0.1/106, or < 0.1/106/year respectively. The 2 latter incidence groups represented 21% of the patients with 130 histotypes. Published phase III and phase II clinical trials (p<10-6) are significantly higher with sarcomas subtypes with an incidence above 1/106 per. CONCLUSIONS: This nationwide registry of sarcoma patients, with exhaustive histology review by sarcoma experts, shows that the incidence of sarcoma and TIM is higher than reported, and that tumors with a very low incidence (1<106/year) are less likely to be included in clinical trials.
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Sarcoma/epidemiología , Sarcoma/patología , Adolescente , Adulto , Anciano , Femenino , Francia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estudios Prospectivos , Sarcoma/clasificación , Sarcoma/diagnóstico , Organización Mundial de la Salud , Adulto JovenRESUMEN
In glial tumors, the loss of heterozygosity of the 1p and 19q chromosomal arms is thought to be a marker of good prognosis in oligodendroglial tumors. However, 1p and 19q loss of heterozygosity may be telomeric, interstitial, centromeric or affect the whole arm of the chromosome and the associations between these different patterns and tumor type, other molecular markers and patient prognosis remain unclear. We analyzed microsatellite markers in a region spanning the chromosome from the telomere to the centromere, to characterize the pattern of 1p and 19q loss of heterozygosity in 39 infiltrative gliomas, including astrocytomas, glioblastomas, oligoastrocytomas and oligodendrogliomas. We then studied the association between loss of heterozygosity and the expression of p53 protein and Olig2, as analyzed using immunohistochemistry, and epidermal growth factor receptor (EGFR) gene amplification, as investigated using fluorescence in situ hybridization (FISH). Finally, we assessed the influence of molecular markers on the overall survival of patients. We identified five different 1p19q loss of heterozygosity patterns among the tumors studied and found that loss of heterozygosity over the whole 1p arm was associated with loss of heterozygosity over the whole 19q arm in 90% of cases. 1p19q whole loss was present in all the classical oligodendrogliomas, whereas other 1p19q loss patterns predominated in oligoastrocytomas. 1p19q whole loss was also significantly associated with Olig2 overexpression, but was never observed in tumors overexpressing p53 protein. We also found that, among patients with contrast-enhancing tumors, those with 1p19q whole loss tended to survive for longer. In combination with classical histological and immunohistochemical data, 1p19q status determination provides pertinent information useful for (1) discriminating between histological types of gliomas and (2) identifying a subgroup of tumors that are associated with a better prognosis.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Glioma/genética , Proteínas del Tejido Nervioso/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 19/genética , Receptores ErbB/genética , Femenino , Amplificación de Genes , Glioma/mortalidad , Glioma/patología , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Pérdida de Heterocigocidad , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Factor de Transcripción 2 de los Oligodendrocitos , Reacción en Cadena de la Polimerasa , PronósticoAsunto(s)
Quistes/patología , Lipoma/patología , Neoplasias Faríngeas/patología , Adipocitos/ultraestructura , Adulto , Antígenos CD34/análisis , Biomarcadores de Tumor/análisis , Quistes/química , Quistes/diagnóstico , Células Gigantes/ultraestructura , Humanos , Lipoma/química , Lipoma/diagnóstico , Masculino , Proteínas de Neoplasias/análisis , Neoplasias Faríngeas/química , Neoplasias Faríngeas/diagnósticoRESUMEN
This case-report studies the clinical, radiological, anatomopatholo-gical and therapeutic aspects of peripheral primitive neuroectodermal tumours (PNET). PNET are neoplasms with a similar histology to tumours in the Ewing family. Diagnosis requires histopathology, immunohistochemistry and cytogenetic studies. To our knowledge, this rare tumour has never been reported in the mesocolon (our case). The treatment, which is usually similar to that for Ewing's sarcoma is complex and has not yet been codified, which is another difficult aspect of this disease with a poor prognosis.
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Mesocolon/patología , Neoplasias Peritoneales/diagnóstico , Sarcoma de Ewing/diagnóstico , Antígeno 12E7 , Antígenos CD/análisis , Moléculas de Adhesión Celular/análisis , Resultado Fatal , Reordenamiento Génico/genética , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Sarcoma de Ewing/genética , Sarcoma de Ewing/secundario , Translocación Genética/genéticaRESUMEN
Gliomas and glioneuronal tumors are histologically polymorphous tumors. They can harbor a clear cell "oligodendroglial-like" component that can be difficult to distinguish from tumor cells of oligodendrogliomas or neurons, particularly on small samples. Thus, knowledge of the pattern of molecular markers in different tumor cell components is essential to ensure reliable diagnosis. Here, we screened 14 pilocytic astrocytomas (PA), 12 gangliogliomas, and 13 oligodendrogliomas for the KIAA1549-BRAF fusion gene, IDH1/2 mutations, and 1p19q losses in various areas of interest representative of the different tumor cell components. Molecular patterns were analyzed according to histologic type, tumor cell components, and clinical data. The KIAA1549-BRAF fusion gene was detected only in 8 out of 11 PAs (73%) and in 3 out of 9 gangliogliomas (33%) (P=0.003). Interestingly, all of the studied areas of interest within the same tumor exhibited the same KIAA1549-BRAF fusion gene status. IDH1-R132H and 1p19q loss were found only in 12 out of the 13 oligodendrogliomas (P<0.0001). Our study shows that cellular polymorphism in PAs and gangliogliomas does not affect the results of molecular analysis investigating the status of the KIAA1549-BRAF fusion gene. Thus, this molecular analysis can be reliably used even if the sample size is limited and the selection of different tumor areas is not possible.
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Astrocitoma/genética , Biomarcadores de Tumor/análisis , Ganglioglioma/genética , Oligodendroglioma/genética , Astrocitoma/diagnóstico , Astrocitoma/fisiopatología , Biomarcadores de Tumor/genética , Femenino , Ganglioglioma/diagnóstico , Ganglioglioma/fisiopatología , Humanos , Inmunohistoquímica , Masculino , Análisis por Micromatrices , Biología Molecular , Oligodendroglioma/diagnóstico , Oligodendroglioma/fisiopatología , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
Onychomatricoma is a rare fibroepithelial lesion of the nail matrix with peculiar clinical and histological features. Clinically, it is characterized by a longitudinal band of yellow thickening of the nail plate with transverse overcurvature and splinter hemorrhages. Nail avulsion exposes a villous tumor of the matrix with filamentous digitations extending into multiple holes of the nail plate. Histologically, a thick keratogenous zone forms a thickened nail plate. The lesion in its proximal portion is characterized by deep epithelial invaginations and by a stroma organized in two layers. The distal zone corresponds to multiple fibroepithelial projections extending into the nail plate. The diagnosis can be difficult in the presence of misleading clinical features or when the specimen is incomplete or examined with an improper orientation. Surgical resection is the recommended treatment.
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Enfermedades de la Uña/patología , Neoplasias Cutáneas/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The EGFR (epidermal growth factor receptor) is involved in the oncogenesis of many tumors. In addition to the full-length EGFR (isoform a), normal and tumor cells produce soluble EGFR isoforms (sEGFR) that lack the intracellular domain. sEGFR isoforms b, c and d are encoded by EGFR variants 2 (v2), 3 (v3) and 4 (v4) mRNA resulting from gene alternative splicing. Accordingly, the results of EGFR protein expression analysis depend on the domain targeted by the antibodies. In meningiomas, EGFR expression investigations mainly focused on EGFR isoform a. sEGFR and EGFRvIII mutant, that encodes a constitutively active truncated receptor, have not been studied. In a 69 meningiomas series, protein expression was analyzed by immunohistochemistry using extracellular domain targeted antibody (ECD-Ab) and intracellular domain targeted antibody (ICD-Ab). EGFRv1 to v4 and EGFRvIII mRNAs were quantified by RT-PCR and EGFR amplification revealed by MLPA. Results were analyzed with respect to clinical data, tumor resection (Simpson grade), histological type, tumor grade, and patient outcome.Immunochemical staining was stronger with ECD-Ab than with ICD-Ab. Meningiomas expressed EGFRv1 to -v4 mRNAs but not EGFRvIII mutant. Intermediate or high ECD-Ab staining and high EGFRv1 to v4 mRNA levels were associated to a better progression free survival (PFS). PFS was also improved in women, when tumor resection was evaluated as Simpson 1 or 2, in grade I vs. grade II and III meningiomas and when Ki67 labeling index was lower than 10%. Our results suggest that, EGFR protein isoforms without ICD and their corresponding mRNA variants are expressed in meningiomas in addition to the whole isoform a. EGFRvIII was not expressed. High expression levels seem to be related to a better prognosis. These results indicate that the oncogenetic mechanisms involving the EGFR pathway in meningiomas could be different from other tumor types.
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Receptores ErbB/metabolismo , Meningioma/metabolismo , Empalme Alternativo/fisiología , Femenino , Francia , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Isoformas de Proteínas/metabolismo , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The epidermal growth factor receptor (EGFR) gene encodes four alternatively spliced mRNA, variants 1, 2, 3 and 4, respectively, encoding the whole isoform a (EGFR) and truncated isoforms b, c and d, all of which lack the receptor's intracellular domain. In addition, a mutant EGFRvIII differs from isoform a in a truncated extracellular domain. The expression pattern of these isoforms is unknown in adult diffuse gliomas. Thus, we investigated in 47 cases: i) EGFR protein expression by immunohistochemistry using an extracellular domain-recognizing antibody (Ext-Ab) and an intracellular domain specific one (Int-Ab), ii) mRNA expression of EGFRv1, -v2, -v3, -v4 and -vIII by RT-PCR and iii) EGFR amplification by fluorescent in situ hybridization. The relation of these data with histological criteria and patient outcome was studied. The immunostaining was stronger with the Ext-Ab than with the Int-Ab. EGFRv1, -v2, -v3 and -v4 mRNA expression were highly correlated. They were expressed in all tumors, with highest levels in glioblastomas. EGFRv1 strong levels and the presence of vIII mRNAs were more closely associated with Int-Ab staining. EGFR gene amplification concerned only glioblastomas and was associated with the presence of EGFRvIII and high levels of EGFRv2, -v3 and -v4 transcripts. A pejorative outcome was associated with: histology (glioblastomas), EGFR amplification, strong Int-Ab labeling and high levels of variant mRNAs. Our results indicated that the full-length EGFR and mutant EGFRvIII are not the sole EGFR isoform expressed in diffuse gliomas. This could explain discordant immunohistochemical results reported in the literature and may have therapeutic implications.
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Neoplasias Encefálicas/genética , Receptores ErbB/genética , Glioma/genética , Adulto , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Receptores ErbB/metabolismo , Femenino , Glioma/metabolismo , Glioma/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Isoformas de Proteínas , Estructura Terciaria de Proteína , ARN Mensajero/genética , Tasa de SupervivenciaRESUMEN
Neuroepithelial papillary tumor of the pineal region (PTPR) has been defined as a distinct entity that is increasingly being recognized, with 96 cases now reported. This tumor shares morphologic features with both ependymomas and choroid plexus tumors. PTPR is characterized by an epithelial-like growth pattern in which the vessels are covered by layers of tumor cells forming perivascular pseudorosettes. These tumors exhibit various combinations of papillary and solid architecture, making the differential diagnosis of PTPR difficult to establish. We report the detailed description of the histopathologic features of a large series of PTPRs from 20 different centers and distinguish 2 subgroups of tumors with either a striking papillary growth pattern or a papillary and solid growth pattern. We highlight the findings that PTPRs have unusual vessels with multiple lumina and frequently show detachment of the border of the tumoral cells from the vascular wall. The 2 PTPR subgroups present similar clinical characteristics and immunophenotypes. We confirmed and extended the results of previous ultrastructural studies on the presence of intercellular junctions at the apical part of tumoral cells. The expression of the tight junction proteins claudin-1, claudin-2, and claudin-3 was investigated by immunohistochemistry. Claudin-1 and claudin-3, but not claudin-2, were expressed in PTPRs and in the fetal subcommissural organ, potentially the origin of this tumor. In contrast, all 3 claudins were expressed in choroid plexus papillomas. Claudin expression may help in the diagnosis of PTPRs and can be used in combination with other markers, such as CK18, NCAM, E-cadherin, MAP-2, and Kir 7.1.
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Carcinoma Papilar/patología , Claudinas/metabolismo , Pinealoma/patología , Uniones Estrechas/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Carcinoma Papilar/diagnóstico por imagen , Carcinoma Papilar/metabolismo , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pinealoma/metabolismo , Pinealoma/cirugía , Uniones Estrechas/ultraestructura , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: The alpha-internexin (INA) gene encodes an intermediate filament involved in neurogenesis and maps in 10q24.33. A strong INA protein expression has been reported in oligodendroglial tumours and was associated with 1p19q deletion. To assess the relevance of INA immunohistochemistry in glioma typing, this paper studied the relationship between INA expression, histological type, genomic status and patient outcome. METHODS: The study analysed INA, nestin, Olig2 and p53 expression, loss of heterozygosity of microsatellite markers from telomere to centromere of 10p, 10q, 1p and 19q chromosomes and epidermal growth factor receptor gene (EGFR) amplification in 40 gliomas (five astrocytomas, 12 oligodendrogliomas, 11 oligoastrocytomas, 12 glioblastomas). INA expression was scored as absent, weak (<10% of labelled tumour cells) or strong (>10%). RESULTS: Oligodendrogliomas showed strong INA and Olig2 expression, and 1p19q whole loss of heterozygosity (wLOH). Astrocytomas and glioblastomas were characterised by no or weak INA expression, high p53 and nestin expression, 10p10q wLOH, and epidermal growth factor receptor amplification. Most oligoastrocytomas had characteristics of astrocytic tumours. All tumours with strong INA expression retained the 10q chromosome arm and, except for one, had a 1p19q wLOH status. However, despite a strong link between INA expression, 1p19q wLOH and 10q retention, discrepancies were observed in 10% of cases. The presence of INA expression, whether weak or strong, was related to a better prognosis. CONCLUSION: INA expression study can be helpful for glioma typing and prognosis determination in combination with other markers. Nevertheless, INA immunohistochemistry cannot replace the genomic analysis to determine 1p19q and 10p10q status.
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Neoplasias Encefálicas/diagnóstico , Cromosomas Humanos Par 10 , Cromosomas Humanos Par 19 , Cromosomas Humanos Par 1 , Glioma/diagnóstico , Proteínas de Filamentos Intermediarios/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , ADN de Neoplasias/análisis , Femenino , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Glioma/metabolismo , Humanos , Inmunohistoquímica , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Epidermal growth factor receptor (EGFR) is produced during the molecular pathogenesis of glioma, and new anti-EGFR molecules are available for therapeutics. Consequently, analyses of the EGFR gene and protein are frequently used for glioma characterization. We compare the accuracy and the usefulness of 2 currently used techniques for histologic classification of gliomas. Fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) techniques were used to assess EGFR gene amplification and protein abundance in a series of 35 gliomas, including World Health Organization (WHO) grade I, II, and III astrocytomas (AI, AII, AIII), grade II and III tumors with oligodendroglial component (OII, OIII) and grade IV glioblastomas (GBs). EGFR gene amplification was found in one-third of the tumors studied. It was frequent in GB and OIII but was never found in AI, AII, AIII, and OII tumors. IHC and FISH provided similar findings for grade of tumor, despite the fact that, in contrast to the FISH gene amplification, EGFR protein was overexpressed in AIII and in GB. EGFR gene amplification was never observed in tumors not containing EGFR protein: therefore FISH is unnecessary when IHC shows no EGFR protein expression. EGFR gene amplification seems to be restricted to high-grade tumors, WHO grade IV astrocytomas, and grade III oligodendroglial tumors.
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Neoplasias Encefálicas/patología , Receptores ErbB/metabolismo , Glioma/patología , Adolescente , Adulto , Anciano , Niño , Preescolar , Receptores ErbB/genética , Femenino , Amplificación de Genes , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The quantitative analysis of VEGF using ELISA in various subtypes of grade I meningiomas reported higher VEGF contents in meningothelial (2.38 +/- 0.62 pg/microg protein, n = 7), transitional (1.08 +/- 0.21 pg/microg protein, n = 13), and microcystic meningiomas (1.98 +/- 0.87 pg/microg protein, n = 5) as compared with fibrous ones (0.36 +/- 0.09 pg/microg protein, n = 5). In contrast to VEGF, no difference in the concentrations of bFGF was detected. VEGF levels did not correlate with meningioma grade (1.47 +/- 0.23 pg/microg versus 2.29 +/- 0.58 pg/microg for 32 and 16 grade I and II, resp), vascularisation (1.53 +/- 0.41 pg/microg versus 1.96 +/- 0.28 pg/microg for 24 low and 24 high vascularisated tumours, resp), and brain invasion (2.32 +/- 0.59 pg/microg versus 1.46 +/- 0.27 pg/microg for 7 and 41 patients with and without invasion, resp). The ELISA procedure is, thus, an interesting tool to ensure VEGF and bFGF levels in meningiomas and to test putative correlations with clinical parameters. It is, thus, tempting to speculate that ELISA would also be valuable for the quantitative analysis of other angiogenic growth factors and cytokines in intracranial tumours.
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Ensayo de Inmunoadsorción Enzimática/métodos , Factor 2 de Crecimiento de Fibroblastos/análisis , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Factores de Crecimiento Endotelial Vascular/análisis , Adulto , Anciano , Femenino , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Neovascularización Patológica , Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Brefeldin A (BFA), a fungal metabolite known to affect the structure and function of the Golgi apparatus, has recently been shown to induce apoptosis and cell growth inhibition in various human cell lines. Glioblastomas (GB) are cerebral tumors with poor prognosis, which display resistance to current therapies including radio- and chemotherapy. The objective of this study was to investigate BFA effects in three human GB cell lines (SA4, SA146 and U87MG cells). Compared with control cells, about 60% of cell growth inhibition was observed in BFA (100 ng/ml for 24 h)-exposed cells in the three cell lines. Furthermore, in SA4 and SA146 cells, BFA was able to induce a time- and dose-dependent apoptosis detected by DAPI staining, TUNEL assay and flow-cytometric analysis. Since p53 expression was not modified after BFA exposure, BFA-induced apoptosis may follow a p53-independent pathway, as already reported. In the same way, BFA did not alter Bcl-2, Bax and Mcl-1 expression. Cell cycle analysis revealed a cell cycle arrest in early G0/G1 phase with an increase in G0/G1 cell population (70% in control cells vs. 83% in exposed cells) associated with a decrease in the S cell population (14% in control cells vs. 5.5% in exposed cells). The Ki67 labeling index also confirmed the cell cycle blockade. Our results suggest that BFA may be a potent cell cycle modulator and inducer of apoptosis in GB cell lines, and therefore may become a promising candidate for the chemotherapeutic treatment of gliomas.