Tchao Meatchi

Assistance Publique – Hôpitaux de Paris, Lutetia Parisorum, Île-de-France, France

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Publications (40)206.85 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D are found in aldosterone-producing adenoma. In addition, adrenals with aldosterone-producing adenomas show cortical remodeling and frequently multiple secondary nodules. Our aim was to investigate whether different aldosterone-producing nodules from the same adrenal share the same mutational status. Aldosterone synthase expression was assessed in multinodular adrenals from 27 patients. DNA of 37 aldosterone-producing secondary nodules was extracted from formalin-fixed paraffin-embedded tissues and genotyped for KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations. Among 17 adrenals with a somatic mutation in the principal nodule, 4 showed the same mutation in a secondary nodule, whereas 10 had no mutation in any of the known genes. In 1 adrenal harboring the KCNJ5 p.Gly151Arg mutation in the principal nodule, the same mutation was present in 2 secondary nodules, but no mutation was found in a third nodule. Finally, in 2 adrenals with a CACNA1D mutation in the principal nodule, a KCNJ5 mutation was identified in the secondary nodule. Among 10 adrenals without mutations in the principal nodule, 1 carried a KCNJ5 mutation in the secondary nodule. No mutations were detected in 7 aldosterone-producing cell clusters from 6 adrenals. No association was observed between the presence of mutations in secondary nodules and clinical parameters. In conclusion, different mutations are found in different aldosterone-producing nodules from the same adrenal, suggesting that somatic mutations are independent events triggered by mechanisms that remain to be identified.
    Hypertension 09/2015; 66(5). DOI:10.1161/HYPERTENSIONAHA.115.05993 · 6.48 Impact Factor
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    ABSTRACT: Introduction: The role of serological tests such as IgA anti-transglutaminase autoantibodies has become increasingly important in celiac disease (CD) diagnosis. However, the efficiency of these tests for patient follow-up is controversial. We investigated the correlation of 12 different serological tests, including recent deamidated gliadin and actin IgA tests, with villous atrophy (VA) in a retrospective cohort of treated celiac patients. Materials and methods: Serum samples were collected from 100 treated CD patients who had intestinal biopsy in the course of their follow-up. Antibodies against transglutaminase, deamidated gliadin peptides, and native gliadin were measured, along with IgA anti-actin. The biopsy slides were all blind-reviewed and scored according to Marsh classification. Results: For all deamidated gliadin and transglutaminase tests, we found that a positive result was significantly associated with persistence of intestinal VA, with a diagnostic efficacy up to 80%. Furthermore, antibodies titers directly correlated with the degree of VA, indicating a strong link between disease activity and presence of antibodies in the serum. Interestingly, the tests with the highest association with persistent VA were those for deamidated gliadin IgG. Using a test positivity pattern analysis, we were also able to identify several groups of patients with distinct antibody profiles that showed significant differences in intestinal damage and diet compliance. Conclusions: Altogether, these results show that deamidated gliadin antibodies are strongly correlated with VA and should be considered valuable tools in CD follow-up and that multiplex serologic analysis for treated CD represents a promising tool for personalized patient management.
    PLoS ONE 09/2015; 10(8):e0136745. DOI:10.1371/journal.pone.0136745 · 3.23 Impact Factor
  • C. Duparc · J. Wils · F. Gobet · T. Meatchi · M.C. Zennaro · E. Louiset · H. Lefebvre ·

  • Article: PP.09.27

    Journal of Hypertension 06/2015; 33:e215-e216. DOI:10.1097/01.hjh.0000468004.04564.fb · 4.72 Impact Factor
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    ABSTRACT: The current pathological diagnosis of Aldosterone Producing Adenoma (APA) is limited to the description of nodules and/or hyperplasia in the resected adrenal gland, independent of their functional characteristics. The aim of our study was to characterize histopathological markers to confirm the presence and identify the sites of aldosterone production and to discriminate KCNJ5-related APA. We investigated eighteen adrenals with APA and fifteen with non-functioning adrenal incidentaloma (NFAI) for expression of Disabled-2 and GIRK4, two markers of zona glomerulosa (ZG), and 77 adrenals with APA with known mutational status for GIRK4 expression. Two-thirds of APA and only one NFAI exhibited both GIRK4 and Disabled-2 membrane staining, allowing to correctly classify 79% of adenomas. Remarkably, 28/32 APA with KCNJ5 mutations exhibited lower GIRK4 expression in APA relative to peritumoral ZG. This was highly specific for KCNJ5 mutations, indicating that GIRK4 immunohistochemistry might be used for initial screening of the somatic mutation status. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Molecular and Cellular Endocrinology 01/2015; 408. DOI:10.1016/j.mce.2015.01.020 · 4.41 Impact Factor
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    ABSTRACT: Context: Adrenal mast cells can stimulate aldosterone secretion through local release of serotonin (5-HT) and activation of the 5-HT4 receptor (5-HT4). In aldosterone-producing adenoma (APA), 5-HT4 receptor is overexpressed and administration of 5-HT4 receptor agonists to patients with APA increases plasma aldosterone levels. These data and the well-documented role of mast cells in tumorigenesis suggest that mast cells may be involved in the physiopathology of APA. Objective: The study aimed at investigating the occurrence of mast cells in a series of APA tissues and to examine the influence of mast cells on aldosterone secretion. Design: The occurrence of mast cells in APAs was investigated by immunohistochemistry. Mast cell densities were compared with clinical data. The influence of mast cells on aldosterone production was studied by using cultures of human mast cell and adrenocortical cell lines. Results: In APA tissues, the density of mast cells was found to be increased in comparison with normal adrenals. Mast cells were primarily observed in adrenal cortex adjacent to adenomas or in the adenomas themselves, distinguishing two groups of APAs. A subset of adenomas was found to contain a high density of intratumoral mast cells which was correlated with aldosterone synthase expression and in vivo aldosterone secretory parameters. Administration of conditioned medium from cultures of human mast cell lines to human adrenocortical cells induced a significant increase in aldosterone synthase (CYP11B2) mRNA expression and aldosterone production. Conclusion: APA tissues commonly contain numerous mast cells which may influence aldosterone secretion through local release of regulatory factors.
    Journal of Clinical Endocrinology &amp Metabolism 01/2015; 100(4):jc20143660. DOI:10.1210/jc.2014-3660 · 6.21 Impact Factor
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    ABSTRACT: Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D have been described in aldosterone-producing adenomas (APAs). Our aim was to investigate the prevalence of somatic mutations in these genes in unselected patients with APA (n=474), collected through the European Network for the Study of Adrenal Tumors. Correlations with clinical and biochemical parameters were first analyzed in a subset of 199 patients from a single center and then replicated in 2 additional centers. Somatic heterozygous KCNJ5 mutations were present in 38% (180/474) of APAs, whereas ATP1A1 mutations were found in 5.3% (25/474) and ATP2B3 mutations in 1.7% (8/474) of APAs. Previously reported somatic CACNA1D mutations as well as 10 novel CACNA1D mutations were identified in 44 of 474 (9.3%) APAs. There was no difference in the cellular composition of APAs or in CYP11B2, CYP11B1, KCNJ5, CACNA1D, or ATP1A1 gene expression in APAs across genotypes. Patients with KCNJ5 mutations were more frequently female, diagnosed younger, and with higher minimal plasma potassium concentrations compared with CACNA1D mutation carriers or noncarriers. CACNA1D mutations were associated with smaller adenomas. These associations were largely dependent on the population structure of the different centers. In conclusion, recurrent somatic mutations were identified in 54% of APAs. Young women with APAs are more likely to be KCNJ5 mutation carriers; identification of specific characteristics or surrogate biomarkers of mutation status may lead to targeted treatment options.
    Hypertension 05/2014; 64(2). DOI:10.1161/HYPERTENSIONAHA.114.03419 · 6.48 Impact Factor
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    ABSTRACT: Somatic mutations of KCNJ5, coding for the potassium channel GIRK4, have recently been implicated in the formation of aldosterone producing adenoma (APA). While a causal link between KCNJ5 mutations, membrane depolarization and aldosterone production has been established, the precise mechanism by which these mutations promote cell proliferation and APA formation remains unclear. The aim of our study was to correlate KCNJ5 mutation status with morphological and functional characteristics of the adrenal cortex adjacent to APA. While GIRK4 was expressed in APA and in the zona glomerulosa of the adjacent cortex, significantly lower levels were detected in APA harboring a KCNJ5 mutation. There was no correlation between KCNJ5 mutation status and the morphological measures of adrenal cortex remodeling, including nodulation, vascularization and expression of CYP11B2. The cell composition of APA was not significantly different between groups. These results indicate that KCNJ5 mutations are not correlated with adrenal cortex remodeling in APA.
    Molecular and Cellular Endocrinology 01/2013; 371(1-2). DOI:10.1016/j.mce.2013.01.018 · 4.41 Impact Factor

  • Annales d Endocrinologie 09/2012; 73(4):265. DOI:10.1016/j.ando.2012.07.100 · 0.87 Impact Factor

  • Annales d Endocrinologie 09/2012; 73(4):342. DOI:10.1016/j.ando.2012.07.804 · 0.87 Impact Factor
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    ABSTRACT: Aldosterone producing adenoma (APA) is the most common form of surgically curable hypertension. To further understand mechanisms involved in APA formation, we investigated the expression of molecules linked to adrenal stem/precursor cells [β-catenin, Sonic hedgehog (Shh), CD56], and nuclear receptors that play key roles in adrenocortical development and function steroidogenic factor 1, dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1) in six control adrenal glands and 14 adrenals with APA and compared their expression with that of specific markers of zona glomerulosa (ZG) [CYP11B2, Disabled 2 (Dab2)]. Both Dab2 and CD56 were expressed in ZG. Although Dab2 associates uniquely with differentiated ZG cells and its expression is lost when cells transdifferentiate to zona fasciculata (ZF) cells, CD56 was also expressed in ZF and in aldosterone-producing cell clusters, confirming that these structures possess an intermediate phenotype between ZG and ZF cells. Shh was barely detectable in cells located to the outer part of the ZG in the control adrenal; in contrast, its expression was detected in the entire APA and was dramatically increased in the hyperplastic peritumoral ZG. Transcriptome profiling revealed differential expression of components of Shh signaling pathway in a subgroup of APA. Similarly, Wnt/β-catenin signaling was activated in the majority of APA as well as in the entire peritumoral adrenal cortex; however, no mutation was identified in the CTNNB1 gene that could account for β-catenin activation. Our data suggest that both APA and adjacent ZG present characteristics of stem/precursor cells; the reexpression of genes involved in fetal adrenal development could underlie excessive ZG cell proliferation and APA formation.
    Endocrinology 12/2011; 152(12):4753-63. DOI:10.1210/en.2011-1205 · 4.50 Impact Factor

  • La Revue de Médecine Interne 12/2011; 32:S277. DOI:10.1016/j.revmed.2011.10.326 · 1.07 Impact Factor
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    ABSTRACT: The prognosis of patients with colorectal cancer has sometimes proved uncertain; thus, the prognostic significance of immune criteria was compared with that of the tumor extension criteria using the American Joint Committee on Cancer/International Union Against Cancer-TNM (AJCC/UICC-TNM) staging system. We studied the intratumoral immune infiltrates in the center of the tumor and in the invasive margin of 599 specimens of stage I to IV colorectal cancers from two independent cohorts. We analyzed these findings in relation to the degree of tumor extension and to the frequency of recurrence. Growth of the primary tumor and metastatic spread were associated with decreased intratumoral immune T-cell densities. Sixty percent of patients with high densities of CD8(+) cytotoxic T-lymphocyte infiltrate presented with stage Tis/T1 tumor, whereas no patients with low densities presented with such early-stage tumor. In patients who did not relapse, the density of CD8 infiltrates was inversely correlated with T stage. In contrast, in patients whose tumor recurred, the number of CD8 cells was low regardless of the T stage of the tumor. Univariate analysis showed that the immune score was significantly associated with differences in disease-free, disease-specific, and overall survival (hazard ratio [HR], 0.64, 0.60, and 0.70, respectively; P < .005). Time-dependent receiver operating characteristic curve analysis illustrated the predictive accuracy of the immune parameters (c-index = 65.3%, time-dependent c-index [Cτ] = 66.5%). A final stepwise model for Cox multivariate analysis supports the advantage of the immune score (HR, 0.64; P < .001; Cτ = 67.9%) compared with histopathologic features in predicting recurrence as well as survival. Assessment of CD8(+) cytotoxic T lymphocytes in combined tumor regions provides an indicator of tumor recurrence beyond that predicted by AJCC/UICC-TNM staging.
    Journal of Clinical Oncology 02/2011; 29(6):610-8. DOI:10.1200/JCO.2010.30.5425 · 18.43 Impact Factor
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    ABSTRACT: In adrenocortical tumors (ACT), Wnt/β-catenin pathway activation can be explained by β-catenin somatic mutations only in a subset of tumors. ACT is observed in patients with familial adenomatous polyposis (FAP) with germline APC mutations, as well as in patients with Beckwith-Wiedemann syndrome with Wilms' tumors reported to have WTX somatic mutations. Both APC and WTX are involved in Wnt/β-catenin pathway regulation and may play a role in ACT tumorigenesis. The aim of this study was to report if APC and WTX may be associated with FAP-associated and sporadic ACT. ACTs from patients with FAP and sporadic adrenocortical carcinomas (ACC) with abnormal β-catenin localization on immunohistochemistry but no somatic β-catenin mutations were studied. APC was analyzed by denaturing high-performance liquid chromatography followed by direct sequencing and by multiplex ligation-dependent probe amplification when allelic loss was suspected. WTX was studied by direct sequencing. Four ACTs were observed in three patients with FAP and were ACC, adrenocortical adenoma, and bilateral macronodular adrenocortical hyperplasia, all with abnormal β-catenin localization. Biallelic inactivation of APC was strongly suggested by the simultaneous existence of somatic and germline alterations in all ACTs. In the 20 sporadic ACCs, a silent heterozygous somatic mutation as well as a rare heterozygous polymorphism in APC was found. No WTX mutations were observed. ACT should be considered a FAP tumor. Biallelic APC inactivation mediates activation of the Wnt/β-catenin pathway in the ACTs of patients with FAP. In contrast, APC and WTX genetic alterations do not play a significant role in sporadic ACC.
    Clinical Cancer Research 10/2010; 16(21):5133-41. DOI:10.1158/1078-0432.CCR-10-1497 · 8.72 Impact Factor
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    ABSTRACT: Primary aldosteronism is the most common form of secondary hypertension with hypokalemia and suppressed renin-angiotensin system caused by autonomous aldosterone production. Our aim was to compare zona glomerulosa (ZG) structure and function between control adrenals and the peritumoral tissue from patients operated on for aldosterone-producing adenoma. ZG morphology and CYP11B1, CYP11B2, and disabled 2 expression were studied in 15 control adrenals and 25 adrenals with aldosterone-producing adenoma. A transcriptome analysis was done using publicly available data sets. In control adrenals, ZG was discontinuous, and CYP11B2 expression was focal or partly continuous and localized to 3 structures, foci, megafoci, and aldosterone-producing cell clusters. CYP11B2 expression was restricted to a limited number of ZG cells expressing Dab2 but not CYP11B1; aldosterone-producing cell clusters were composed of cells with an intermediate phenotype expressing CYP11B2 but not disabled 2 or CYP11B1. In peritumoral tissue, large remodeling of the adrenal cortex was observed with increased nodulation and decreased vascularization that were not correlated with CYP11B2 expression. In 17 out of 25 adrenals, hyperplasia of adjacent ZG was observed with persistent expression of CYP11B2 that was extended to the entire ZG. In all of the adrenals from patients with aldosterone-producing adenoma, CYP11B2 expression was present in foci, megafoci, and aldosterone-producing cell clusters. Transcriptome profiling indicates a close relationship between peritumoral and control adrenal cortex. In conclusion, adrenal cortex remodeling, reduced vascularization, and ZG hyperplasia are major features of adrenals with aldosterone-producing adenoma. Transcriptional phenotyping is not in favor of this being an intermediate step toward the formation of aldosterone-producing adenoma.
    Hypertension 10/2010; 56(5):885-92. DOI:10.1161/HYPERTENSIONAHA.110.158543 · 6.48 Impact Factor
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    ABSTRACT: KRAS mutations are a strong predictive marker of resistance to anti-epidermal growth factor receptor (EGFR) antibodies in advanced colorectal cancer (CRC) but only a subset of wild-type (WT) KRAS patients are responders, suggesting the existence of additional markers of resistance to this treatment. The activation of EGFR downstream signaling pathways may be one of these ones. In a series of 42 patients with advanced CRC treated with cetuximab/panitumumab, for whom KRAS status was previously determined, we retrospectively analyzed the intratumor expression of EGFR downstream signaling phosphoproteins of the RAS/MAPK and PI3K/AKT pathways (pERK1/2, pMEK1, pAKT, pP70S6K and pGSK3beta) using Bio-Plex phosphoprotein array. Association with tumor response, progression-free survival (PFS) and overall survival (OS) was assessed. The expression of all the phosphoproteins was higher in KRAS mutated tumors than in WT tumors. The expression of pP70S6K was lower in responders than in nonresponder patients. In univariate analysis, patients with high pMEK1 or pP70S6K expression had a shorter PFS than those with low expression. Patients with high pP70S6K expression also had a shorter OS. In multivariate analysis, PFS was shorter for patients with high pMEK1 or pP70S6K expression, independently of KRAS status, as OS for patients with high pP70S6K expression. Therefore, WT KRAS patients with high pP70S6K expression had a shorter survival than those with low expression. Our results suggest the importance of EGFR downstream signaling phosphoproteins expression in addition to KRAS status to define the subgroup of patients who will not benefit from anti-EGFR therapy.
    International Journal of Cancer 09/2010; 127(6):1321-31. DOI:10.1002/ijc.25152 · 5.09 Impact Factor
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    ABSTRACT: Background: Hypertension remains a major risk factor for development of congestive heart failure. Better diagnostic tools for identification of asymptomatic hypertensive patients at particular high risk for development of heart failure are needed. Methods: Impact of left ventricular hypertrophy (LVH) on electrocardiogram (ECG), echocardiography or both on rate of combined cardiovascular death, stroke and myocardial infarction (primary endpoint) and hospitalized heart failure (secondary endpoint) was assessed in 922 hypertensive patients in the Losartan Intervention For Endpoint reduction in hypertension echocardiography substudy. LVH was diagnosed by Sokolow Lyon and Cornell product criteria on ECG and as LV mass index >116 g/m2 in men and >104 g/m2 in women by echocardiography. Results: 172 patients had LVH only on ECG, 135 only on echocardiogram, 515 on both and 100 on neither. Patients with LVH on both tests were older, more obese, had higher systolic blood pressure and LV mass, lower LV systolic function and included more patients with aortic regurgitation and history of ischemic heart disease (all p < 0.05). Incidence of the primary endpoint over 4.8 years study treatment did not differ among groups. Incidence of hospitalization for heart failure was 5.3 and 2.6 times higher, respectively, in patients with LVH on both tests compared to patients with LVH on ECG or echocardiogram only (p < 0.01). In Cox regression, LVH on both tests predicted hospitalization for heart failure [HR 4.46 (95% CI 1.31–15.20), p = 0.019] independent of LV ejection fraction, study treatment, in-treatment systolic blood pressure and history of ischemic heart disease. Conclusion: Performing echocardiography in hypertensive patients with ECG LVH helps identify patients with lower LV systolic function and higher risk for hospitalized heart failure. Combined use of ECG and echocardiography is suggested to better identify asymptomatic hypertensive patients at high risk for heart failure.
    Journal of Hypertension 06/2010; 28. DOI:10.1097/01.hjh.0000378860.58825.80 · 4.72 Impact Factor
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    ABSTRACT: Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma–paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma–paraganglioma syndrome is often unrecognised, although 10–30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. Despite these figures, the screening of phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect phaeochromocytoma–paraganglioma syndrome is rarely done because of time and financial constraints. We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series.
    The Lancet Oncology 09/2009; 10(8):764-71. DOI:10.1016/S1470-2045(09)70164-0 · 24.69 Impact Factor
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    ABSTRACT: The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print., *2007 Journal Citation Report (Thomson Reuters, 2008)
    The American Journal of Gastroenterology 05/2009; 104(4):1069. DOI:10.1038/ajg.2009.56 · 10.76 Impact Factor
  • E Samaha · G Rahmi · B Landi · T Méatchi · C Cellier ·

    Gastroentérologie Clinique et Biologique 04/2009; 33(4):247-52. · 1.14 Impact Factor

Publication Stats

1k Citations
206.85 Total Impact Points


  • 2015
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2008-2015
    • Université René Descartes - Paris 5
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
  • 2002-2014
    • Hôpital Européen Georges-Pompidou (Hôpitaux Universitaires Paris-Ouest)
      • Service d’Anatomie-Pathologie
      Lutetia Parisorum, Île-de-France, France
  • 2010-2013
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France