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Dominique Figarella-Branger

Publications and source records attributed to Dominique Figarella-Branger.

At least 37 records · Page 2Linked to original sources
PubMed2005

Lack of alkaline phosphatase activity predicts meningioma recurrence.

Meningiomas usually are benign intracranial tumors. However, some recur despite gross total resection, invade surrounding structures, or, rarely, metastasize. Reduced expression of the nonspecific tissue-type alkaline phosphatase (Pal) has been reported in high-grade meningiomas. To search for a predictor for recurrence, we studied Pal expression by histoenzymology in a series of 54 meningiomas with gross total removal. Pal expression was mostly altered in grades II and III meningiomas (P = .000014) and meningiomas with high MIB-1 values (P = .001). Pal expression correlated with cytogenetic data (P = .000033) and with recurrence (P = .0064); all tumors that recurred had abnormal Pal expression (13/13). In univariate analysis, Pal expression was the only variable correlated with recurrence-free survival (P = .035). Histochemical detection of Pal is a useful, easy, and low-cost technique to predict recurrence in meningiomas.

Adult↗
PubMed2005

[Histological classification of human gliomas: state of art and controversies].

The histological classification of human gliomas remains in 2005 a challenge. The aim is to define the histological type of glioma (astrocytic, oligodendrocytic or mixed) and the grade in order to classify the patients and give them an accurate treatment. Although the standard remains the WHO classification, this classification suffered from lack of reproducibility among pathologists. In particular this classification does not take into account the intrinsic morphological heterogeneity of infiltrative gliomas and does not discriminate the tumour cells from the residual brain parenchyma. According to the WHO classification, infiltrative gliomas encompass astrocytic gliomas (diffuse astrocytomas grade II, anaplastic astrocytomas grade III and glioblastomas grade IV), oligodendroglial tumours (oligodendrogliomas grade II, anaplastic oligodendrogliomas grade III) and mixed gliomas (oligoastrocytomas grade II and anaplastic oligoastrocytomas grade III). Circumscribed gliomas mainly corresponds to pilocytic astrocytomas (grade I). In contrast, the Sainte Anne classification takes into account the macroscopic informations provided by imaging techniques and the tumour growth patterns. Three distinct tumour growth patterns may be seen in gliomas, type I: tumor tissue only, type II: tumour tissue and isolated tumor cells permeating the brain parenchyma (ITC) and type III: ITCs only and no tumor tissue. According to the Sainte Anne classification, gliomas are divided into astrocytic gliomas (pilocytic astrocytomas, structure type I, glioblastomas structure type II) and oligodendrogliomas and mixed oligoastrocytomas (grade A: lack of contrast enhancement and lack of endothelial hyperplasia, structure type III; and grade B: contrast enhancement or endothelial hyperplasia, structure type II and III). In the future the glioma classification has to be unique and should take into account clinical data, neuroradiological and histological features and results of molecular biology.

Astrocytoma↗
PubMed2005

[Role of adrenomedullin in glioblastomas growth].

Glioblastoma multiforme is the most malignant of the primary brain tumors and is almost always fatal. The treatment strategies for this disease have not changed appreciably for many years and most are based on a limited understanding of the biology of the disease. Growth factors are potential targets for therapeutic strategies because they are essential for tumor growth and progression. Adrenomedullin (AM) is a multifunctional regulatory peptide with mitogenic and angiogenic capabilities among others. Real-time quantitative reverse transcriptase-polymerase chain reaction analysis showed that AM mRNA was correlated to the tumor type and grade, with high expression in all glioblastomas analysed, whereas a low expression was found in anaplastic astrocytomas and barely detectable levels in low-grade astrocytomas and oligodendriogliomas. The correlation of AM expression to the grade of glioma support the hypothesis that AM may participate in the progression of gliomas. We demonstrate that AM may function as an autocrine/paracrine growth factor for glioblastoma cells. The data demonstrated that the anti-AM antibody significantly suppress the growth of established glioblastoma xenografts. The action of AM is specific and is mediated by the calcitonin receptor-like receptor/receptor activity-modifying protein-2 and -3 (CRLR/RAMP2, CRLR/RAMP3). Furthermore, the proangiogenic action of AM on cultured endothelial cells via CRLR/RAMP2 and CRLR/RAMP3 receptors may translate in vivo into enhanced neovascularization and therefore identify AM and its receptors acting as potential new targets for antiangiogenic therapies.

Adrenomedullin↗
PubMed2004

Phase II study of temozolomide without radiotherapy in newly diagnosed glioblastoma multiforme in an elderly populations.

BACKGROUND: Currently, the survival of patients age > 70 years with glioblastoma multiforme (GBM) ranges from 4 months to 6 months, although radiotherapy and/or chemotherapy may prolong survival in certain subgroups. Temozolomide is an oral chemotherapeutic agent with efficacy against malignant gliomas and a favorable safety profile. This open-label, single-center, Phase II study was designed to evaluate the efficacy and safety of temozolomide as first-line chemotherapy and exclusive treatment in elderly patients with newly diagnosed GBM. METHODS: Chemotherapy-naïve patients (age > 70 years) were treated with temozolomide at a dose of 150-200 mg/m(2) per day for 5 consecutive days of a 28-day cycle until they developed disease progression. No radiation therapy was administered. The primary endpoint was median overall survival (OS); secondary endpoints included progression-free survival (PFS) and toxicity. RESULTS: Thirty-two patients (median age, 75 years; median Karnofsky performance status, 70) experienced a median OS of 6.4 months and a median PFS of 5.0 months. Of 29 patients who were assessed for response, 9 patients (31%) achieved a partial response, 12 patients (41%) maintained stable disease, and 8 patients (28%) developed progressive disease. Adverse events primarily were mild, with NCI CTC Grade 3-4 thrombocytopenia and neutropenia reported to occur in 6% and 9% of patients, respectively. No neurotoxicity was observed. Treatment delays and dose reductions occurred in 13% and 14% of cycles, respectively. CONCLUSIONS: Temozolomide represents a safe, easily administered, and effective therapeutic approach for elderly patients with newly diagnosed GBM.

Aged↗
PubMed2004

Multiminicore disease in a family susceptible to malignant hyperthermia: histology, in vitro contracture tests, and genetic characterization.

BACKGROUND: Histological anomalies associated with malignant hyperthermia (MH) have been scarcely reported. In some patients susceptible to MH (MHS), central cores have been identified and a genetic association has been proposed, but multiminicore lesions have not been systematically reported. OBJECTIVE: To analyze the association between multiminicores and MHS in a large family with MH with an approach combining histology, in vitro contracture tests, and genetic analysis. PATIENTS AND METHODS: Twenty-nine members of an MH family (147 members) were investigated. MAIN OUTCOME MEASURES: Muscle biopsy specimens were analyzed histologically and with in vitro contracture tests. Genetic analyses were performed to determine the presence of mutations in the ryanodine receptor (RYR1) gene. RESULTS: According to the gold standard in vitro contracture tests, 17 patients were diagnosed as having MHS and 10 as not being susceptible. Multiminicores were found in 16 of the 17 MHS patients and in a single nonsusceptible participant. A linkage between the MH trait and the RYR1 locus in chromosome 19 was demonstrated, whereas no already known mutations were found. Two missense heterozygous mutations (R2676W and T2787S) were identified from sequencing of the entire coding complementary DNA. Overall, we found a significant association between MHS and the presence of multiminicores (chi(2) = 26.5, P<.001) on the one hand and the presence of new mutations in the RYR1 gene (chi(2) = 19.0, P<.001) on the other hand. This remarkably high occurrence of multiminicores in an MHS family is uncommon, and genetic analyses indicate that the association between multiminicores and MHS is linked to a novel R2656W and T2787S substitution present on the same allele of the RYR1 gene. CONCLUSIONS: These results indicate that multiminicore lesions are observed in MHS patients with neither clinical signs related to multiminicore disease nor histological features of congenital myopathies. These multiminicore lesions may be secondary to mutations in the RYR1 gene. As a consequence, these patients must be distinguished from patients with multiminicore disease and from other MHS patients for whom multiminicores are not observed.

DNA Mutational Analysis↗
PubMed2004

Deletions of chromosomes 1p and 19q are detectable on frozen smears of gliomas by FISH: usefulness for stereotactic biopsies.

Among diffuse gliomas, oligodendrogliomas may account for 25% of cases. They have a better prognosis and chemosensitivity as compared to astrocytomas. Genetic studies have shown a correlation between oligodendrocyte phenotype and presence of 1p/19q deletions. In addition, these deletions are of prognostic value. The aim of the present study was to describe a new method to detect 1p/19q deletions when little tumoral material is available (stereotactic biopsies (SBs)). Since smears (cytological preparations) are routinely done for intraoperative diagnosis of gliomas, we have searched for 1p/19q deletions by FISH in a series of 30 patients with a glioma. In 14 cases, loss of heterozygosity (LOH) analysis was also performed in order to validate our method. We found that FISH analysis on frozen smears was a simple, rapid and reliable method to detect 1p/19q deletions and a good concordance was found with LOH data (85%). The main advantages of FISH analysis on frozen smears are the following. First, it requires little material and can be easily done in the case of SBs. Second, it has a higher sensitivity than LOH especially in infiltrative areas of gliomas. Third, it allows detection of a codeletion 1p/19q in a single tumor cell. In contrast, LOH analysis is easier to interpret and can detect smaller and partial deletion whose pronostic significance remains to be defined. In conclusion, these two techniques can be used to investigate 1p/19q status in gliomas. The appropriate choice of one or other of these two techniques will depend on the specific questions that need to be answered.

Biopsy↗
PubMed2004

Fetal visceral maturation: a useful contribution to gestational age estimation in human fetuses.

With regard to the law, estimating fetal age is essential to assess viability (after 20 weeks according to the WHO) and the proposed methods generally use long bone measurements. Here, we evaluated the accuracy of soft tissue maturational stage and compared it with long bone measurements. First, eight kinds of tissues or organs from 448 fetuses with known medical history were studied (macroscopically or histologically). We clearly demonstrated that adrenal glands and skin were very good age indicators, because some characteristics appeared only after 20 weeks. We established a linear regression with a 95% confidence interval of +/- 2.9 weeks. Second, we applied our original formula using femur measurement and we combined soft tissues and bones in a multiparametric regression. The confidence interval was reduced to +/- 2.5 weeks. We conclude that the pathologist must use both histological and anthropometric data to determine fetal age as accurately as possible.

Femur↗
PubMed2003

MR imaging of acquired fetal brain disorders.

INTRODUCTION: Acquired fetal brain disorders represent the third indication of fetal brain MRI, after ventricular dilatation and malformations of the central nervous system. DISCUSSION: MRI is an adequate imaging technique for evaluating fetal brain damage. Fetal brain response to brain injury may be acute, chronic or a combination of acute and chronic. An acute response is not as common in the fetal brain as in the postnatal period. A chronic response or the combination of chronic and acute response are the most common responses of the fetal brain to injury, whatever its origin. MRI also provides the natural history of acquired fetal brain lesions with regard to the stage of development.

Brain Diseases↗
PubMed2003

Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies.

The inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), and sporadic inclusion-body myositis (s-IBM). In DM, the main immune effector response appears to be humoral and directed against the microvasculature, whereas in both PM and s-IBM, cytotoxic CD8+ T cells and macrophages invade and eventually destroy nonnecrotic muscle fibers expressing major histocompatibility complex class I. The need for more specific and safer therapies in inflammatory myopathies has prompted researchers to better decipher the molecular events associated with inflammation and muscle fiber loss in these diseases. The complex specific migration of leukocyte subsets to target tissues requires a coordinated series of events, namely activation of leukocytes, adhesion to the vascular endothelium, and migration. Cell adhesion molecules (CAM) and chemokines play a major role in this multistep process. In addition, cytokines by stimulating CAM expression and orchestrating T-cell differentiation also influence the immune response. This review focuses on recent advances in defining the molecular events involved in leukocyte trafficking in inflammatory myopathies. Specific topics include a concise summary of clinical features, pathological findings and immunopathology observed in inflammatory myopathies, background information about cytokines, chemokines and cell adhesion molecules, and the expression of these molecules in inflammatory myopathies.

Cell Adhesion Molecules↗
PubMed2003

Neural cell adhesion molecule expression in renal cell carcinomas: relation to metastatic behavior.

Neural cell adhesion molecule (NCAM), a member of the immunoglobulin superfamily, is expressed by a subgroup of renal cell carcinomas (RCCs) and by a limited number of adult organs, including the central nervous system (CNS) and adrenal gland. Because the major function of NCAM is homophilic adhesion between homotypic and heterotypic cells, we hypothesized that NCAM-expressing RCCs should preferentially metastasize to the CNS and adrenal gland. We did a retrospective immunohistochemical analysis of NCAM expression both in 338 primary renal tumors, including 249 conventional RCCs and 31 metastases of conventional RCCs. In primary renal tumors, NCAM was expressed by only 38 (15.2%) conventional RCCs and by no other histological subtypes of renal tumor. This expression correlated with a higher risk of adrenal and CNS metastases (P <0.001). NCAM expression also correlated with tumor size (P <0.001), renal vein involvement (P = 0.02), perirenal invasion (P = 0.02), and Fuhrman grading (P < 0.001). Finally, patients with NCAM-expressing RCCs had a lower survival rate (P = 0.006), especially in the first 2 years after surgery. NCAM expression is of interest both for evaluating the prognosis of patients with conventional RCCs and for determining a subgroup of patients at high risk for adrenal and CNS metastases.

Adolescent↗
PubMed2003

Differential regulation of proopiomelanocortin and pituitary-restricted transcription factor (TPIT), a new marker of normal and adenomatous human corticotrophs.

Since the identification of the pituitary-restricted transcription factor Tpit, a novel T-box factor that is only present in mouse in the two pituitary proopiomelanocortin (POMC)-expressing lineages, no information was available on its pattern of expression in human pituitary. We investigated by immunohistochemistry and in situ hybridization the expression of TPIT in normal human anterior pituitary tissue and in several types of human pituitary adenomas (n = 52). TPIT expression was restricted to the nucleus of normal or adenomatous human corticotroph cells. No specific TPIT immunostaining was detectable in all prolactin (PRL)-, GH-, or gonadotropin-secreting adenomas. In situ hybridization studies demonstrated that TPIT transcripts were coexpressed with POMC mRNA in both secreting and silent corticotroph adenomas, and in normal corticotrophs, whereas TPIT mRNA was not detectable in other types of pituitary adenomas. Unlike POMC, TPIT was not up-regulated by adrenalectomy in rats and did not seem down-regulated in the normal pituitary adjacent to human corticotroph microadenomas. TPIT is the only currently known transcription factor selectively expressed in human normal and adenomatous corticotrophs. In human and experimental models, TPIT and its target gene POMC were thus differentially regulated by glucocorticoids. Moreover, TPIT represents a new marker of POMC-expressing pituitary cells.

Adenoma↗
PubMed2003

Pilocytic astrocytomas in children: prognostic factors--a retrospective study of 80 cases.

OBJECTIVE: Pilocytic astrocytomas (PA) are Grade I brain tumors characterized by an excellent prognosis. In some cases, however, the patient has a bad outcome. The aim of our study was to search for the clinicopathological factors underlying the prognosis for patients with this disease. METHODS: We reviewed the clinical, neuroradiological, and histopathological features of 80 PAs (33 cerebellar, 18 optochiasmatic, 16 brainstem, 7 spinal cord, 3 thalamic, 2 optic nerve, and 1 hemispheric) in pediatric patients. RESULTS: Pathological examination revealed 58 classic PAs and 20 pilomyxoid astrocytomas, which are a histological variant of PAs. Two cases remained unclassified. The mean overall follow-up period was 58 months, the 5-year progression-free survival rate was 75%, and the 5-year survival rates were 100 and 92% after total and partial removal. Univariate statistical analysis revealed that partial resection, optochiasmatic PA localization, and pilomyxoid variant were associated with a worse prognosis, but the latter two parameters were too closely related to the extent of resection to be independent prognostic factors in multivariate analysis. Among the patients who underwent partial surgical removal, only invasion of the surrounding structures was related to prognosis. CONCLUSION: PAs are benign tumors, but some clinicopathological factors, such as partial resection, optochiasmatic location, invasion of surrounding structures, and the pilomyxoid variant, have a worse prognosis.

Adolescent↗
PubMed2003

Use of proton magnetic resonance spectroscopy of the brain to differentiate gliomatosis cerebri from low-grade glioma.

OBJECT: Gliomatosis cerebri (GC), a rare entity characterized by a widespread infiltration of brain by tumor, lacks objective and quantitative diagnostic criteria. Single-voxel spectroscopy and chemical shift imaging (two-dimensional proton magnetic resonance [MR] spectroscopy) were performed using both short (20- or 22-msec) and long (135-msec) echo times in nine patients suffering from GC, nine patients with low-grade gliomas (LGGs), and 25 healthy volunteers to establish the precise metabolic pattern of this uncommon brain neoplasm. METHODS: The gliomatosis infiltration was characterized by markedly elevated levels of creatine-phosphocreatine (Cr) and mvo-inositol (Ins), a reduced level of N-acetyl aspartate (NAA), and a moderately elevated level of choline-containing compounds (Cho). This pattern differs strikingly from LGGs, which are characterized by elevated levels of Cho and Ins, markedly reduced levels of NAA, and low-to-normal Cr concentrations. Although the distinction between GC and LGG, based on histological and MR imaging criteria, is a matter of debate, MR spectroscopy produces valuable information for the differentiation between these two entities and, hence, the choice of therapeutic strategy. It also provides new insight into the pathophysiology of GC because elevated Cr and Ins levels may be related to proliferation of glial elements or, more probably, activation of normal glia. Elevated levels of Cho reflect cellular proliferation and reduced NAA corresponds to reversible neuronal injury and/or focal invasion by the tumor process. CONCLUSIONS: Owing to the unfavorable clinical outcome associated with GC compared with that associated with LGG, the findings of this study illustrate the diagnostic and prognostic value of proton MR spectroscopy in the characterization of infiltrating gliomas.

Adolescent↗
PubMed2003

Polysialylated neural cell adhesion molecules expressed in human pituitary tumors and related to extrasellar invasion.

OBJECT: Pituitary adenomas are usually benign tumors; however, some behave aggressively and metastasize. Until now, no specific marker of aggressive behavior or malignancy has been found. The polysialylated neural cell adhesion molecule (NCAM), which is highly expressed in embryonic tissues such as the brain and pituitary, is detected in some and neuroendocrine tumors. Because polysialylation has been implicated in the regulation of cell growth and migration, polysialylated NCAM expression has been considered as a prognostic marker in such tumors. METHODS: In the present study, the authors analyzed polysialylated NCAM expression in 82 pituitary tumors from humans: 49 secreting adenomas, 32 nonfunctioning adenomas, and one growth hormone and prolactin-secreting carcinoma associated with acromegaly and spinal and liver metastases. Based on immunohistochemical analyses, the tumors were classified as somatotropic (22 tumors), prolactinoma (14 tumors), corticotropic (17 tumors), and gonadotropic or so-called null cell adenomas (28 tumors). Assessment of polysialylated NCAM was performed using three different methods (immunohistochemical analysis, Western blot analysis, and enzyme-linked immunosorbent assay) with a specific mouse monoclonal immunoglobulin M (Men B) that recognizes polysialic acid on NCAM. Tumoral NCAM expression was also evaluated with the aid of immunohistochemical analysis. Using this method, NCAM and polysialylated NCAM were studied in six healthy pituitaries. In addition, correlations were investigated using three statistical methods (chi-square test, nonparametric Mann-Whitney U-test, and principal component analysis) to compare tumoral polysialylated NCAM expression and seven parameters (tumor size and type, intrasphenoidal or cavernous sinus invasion, Ki-67 index, mitoses, and patient age and sex). Neural cell adhesion molecules were expressed in the healthy anterior pituitary and in all tumors. In contrast, polysialylated NCAM was not found in the healthy pituitary gland, but was expressed in 46.3% of typical pituitary tumors and 85% of the tumors selected as highly aggressive, including one carcinoma and three tumors with histological characteristics that raised suspicion of malignancy. There was no significant correlation between polysialylated NCAM expression and tumor size, tumor type, Ki-67 index, mitoses, or patient age and sex. In contrast, the expression of polysialylated NCAM, which was sensitive to endoneuraminidase-N treatment, was strongly correlated with tumor invasion (p < 0.0001). CONCLUSIONS: In pituitary tumors in humans, expression of polysialylated NCAM is strongly related to tumor invasion and confirms the clinical diagnosis of aggressiveness.

Adenoma↗
PubMed2003

Shared oligodendrocyte lineage gene expression in gliomas and oligodendrocyte progenitor cells.

OBJECT: Gliomas (astrocytic and oligodendroglial) are the most frequently occurring primary neoplasms in the central nervous system (CNS). Histological classification, which can be performed to distinguish astrocytomas from oligodendrogliomas, is essentially based on pathological features and has great prognostic and therapeutic value but lacks reproducibility. Specific markers of cell lineage, especially those f or oligodendrogliomas, are still lacking. The oligodendrocyte lineage (OLIG) genes, transcriptional factors of the basic helix-loop-helix family, have been recently identified in oligodendrocyte progenitor cells (OPCs) in the CNS of developing and adult rodents. Data from a few studies have shown in a small series of brain tumors that OLIG genes characterize oligodendrogliomas. To search for a differential expression of the OLIG genes in subgroups of brain tumors, the authors investigated OLIG1 and OLIG2 gene expression. METHODS: Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), the authors analyzed a series of 89 tumors (71 astrocytic and oligodendroglial tumors, eight ependymomas, three medulloblastomas, four meningiomas, and three schwannomas) and normal human brain tissue samples. It was demonstrated that OLIG gene expression was largely limited to glial tumors, that is, astrocytomas and oligodendrogliomas. A very low level was detected in ependymomas, whereas other tumors lacked OLIG gene expression altogether. Surprisingly, OLIG1 and OLIG2 expressionwas not limited to oligodendroglial tumors, but was observed in astrocytic lesions as well, independent of tumor grade. Interestingly, these genes were expressed at the highest level in pilocytic astrocytomas according to semiquantitative RT-PCR results, which were confirmed on dot blot analysis. In situ hybridization showed that the OLIG2 gene was expressed by tumor cells in pilocytic astrocytomas as well as those in oligodendrogliomas. CONCLUSIONS: The OLIG genes are additional markers shared by all gliomas andOPCs. These markers may help to classify gliomas, to improve understanding of their histogenesis, and to identify new therapeutic targets.

Astrocytoma↗
PubMed2003

The usefulness of MR imaging in the diagnosis of dysembryoplastic neuroepithelial tumor in children: a study of 14 cases.

BACKGROUND AND PURPOSE: Dysembryoplastic neuroepithelial tumors (DNTs) are benign lesions affecting children and are associated with epilepsy. The goal of our study was to better characterize the clinical-radiologic-pathologic spectrum of DNTs (complex and simple forms only) in a series of 14 children. METHODS: Clinical, neuroradiologic, and pathologic features of all cases were retrospectively studied. RESULTS: Eleven cases of complex and three cases of simple DNTs were identified. Mean follow-up was 87 months, and no recurrence was recorded except for one case of simple DNT. We found that some neuroradiologic features may be helpful to support the diagnosis of DNT: presence of "septations," triangular pattern of distribution, and absence of contrast enhancement. CONCLUSION: The evidence of the specific glioneuronal element is found by pathologic examination, but the typical neuroradiologic aspect of DNT suggests this diagnosis preoperatively. Radiologic examination may be helpful for the diagnosis of DNT when pathologic findings are inconclusive.

Adolescent↗