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Dive into the research topics where C. Brambilla is active.

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Featured researches published by C. Brambilla.


Modern Pathology | 2000

Pulmonary Pathology of Erdheim-Chester Disease

Walter L. Rush; Jo Ann W Andriko; Françoise Galateau-Sallé; Elizabeth Brambilla; C. Brambilla; I Ziany-bey; Melissa L. Rosado-de-Christenson; William D. Travis

Erdheim-Chester disease (ECD) is a rare non-Langerhans’ cell histiocytosis that may present with pulmonary symptoms. The condition seems to be nonfamilial and typically affects middle-aged adults. Radiographic and pathologic changes in the long bones are diagnostic, but patients often present with extraskeletal manifestations. Advanced pulmonary lesions are associated with extensive fibrosis that may lead to cardiorespiratory failure. The clinical, radiologic, and pathologic features of six patients with ECD with lung involvement are presented. The patients were three men and three women (mean age, 57). Five presented with progressive dyspnea, and one presented with diabetes insipidus. Open-lung biopsies showed histiocytic infiltrates in a lymphangitic pattern with associated fibrosis and lymphoplasmacytic inflammatory infiltrates. The histiocytes did not stain with periodic acid-Schiff. Immunoperoxidase studies performed on specimens from five of six patients showed that the histiocytes were positive for CD68 and Factor XIIIa and negative for CD1a. Specimens from two patients exhibited immunoreactivity for S-100 protein. Electron microscopy studies performed on specimens from two patients showed phagocytic lysosomes but no Birbeck granules. Clinical follow-up of up to 16 years was available. At the end of that time, five patients were dead of complications related to their disease; one patient remains alive 4 years after diagnosis but with severe respiratory compromise. ECD is a rare non-Langerhans’ cell histiocytosis that may present as interstitial lung disease and resemble other pulmonary conditions, particularly usual interstitial pneumonitis and pulmonary Langerhans’ cell histiocytosis. Recognition of this entity will allow better assessment of its true incidence, therapeutic options, and prognosis.


Clinical Cancer Research | 2014

Lung Squamous Cell Carcinomas with Basaloid Histology Represent a Specific Molecular Entity

C. Brambilla; Julien Laffaire; Sylvie Lantuejoul; D. Moro-Sibilot; Hélène Mignotte; François Arbib; Anne-Claire Toffart; Fabien Petel; Pierre Hainaut; Sophie Rousseaux; Saadi Khochbin; Aurélien de Reyniès; Elisabeth Brambilla

Purpose: The basaloid carcinoma (pure) and the (mixed) basaloid variant of lung squamous cell carcinoma (SCC) have a dismal prognosis but their underlying specific molecular characteristics remain obscure and no therapy has proven to be efficient. Experimental Design: To assess their molecular specificity among other lung SCCs we analyzed DNA copy number aberrations and mRNA expression pangenomic profiles of 93 SCCs, including 42 basaloid samples (24 pure, 18 mixed). Results: Supervised analyses reveal that pure basaloid tumors display a specific mRNA expression profile, encoding factors controlling the cell cycle, transcription, chromatin, and splicing, with prevalent expression in germline and stem cells, while genes related to squamous differentiation are underexpressed. From this signature, we derived a 2-genes (SOX4, IVL) immunohistochemistry-based predictor that discriminated basaloid tumors (pure and mixed) from non-basaloid tumors with 94% accuracy in an independent series. The pure basaloid tumors are also distinguished through unsupervised analyses. Using a centroid-based predictor, the corresponding molecular subtype was found in 8 independent public datasets (n = 58/533), and was shown to be associated with a very poor survival as compared with other SCCs (adjusted HR = 2.45; P = 0.000001). Conclusion: This study enlightens the heterogeneity of SCCs that can be subclassified in mRNA expression subtypes. This study demonstrates for the first time that basaloid SCCs constitute a distinct histomolecular entity, which justifies its recognition and distinction from non-basaloid SCCs. In addition, their characteristic molecular profile highlights their intrinsic resistance to cytotoxic chemotherapy and could serve as a guide for targeted therapies. Clin Cancer Res; 20(22); 5777–86. ©2014 AACR.


Lung Cancer | 2001

Bronchorrhea revealing cervix adenocarcinoma metastastic to the lung

Olivier Epaulard; Denis Moro; Thierry Langin; Gilles Devouassoux; C. Brambilla

Copious bronchorrhea can be related to bronchioloalveolar carcinoma, but reports of bronchorrhea related to lung metastasis are rare. We report the case of a woman presenting lung metastases of a cervical adenocarcinoma revealed by bronchorrhea, eventually identified as ectopic cervical mucus. Treatment included anticancer drugs and erythromycin, the latter in order to reduce the bronchorrhea, with eventually poor efficacy. This observation illustrates the importance of respiratory signs in the post-therapeutic follow up of cancer, especially cough and bronchorrhea in adenocarcinoma.


Lung Cancer | 1997

Molecular biology of neuroendocrine lung tumors

E. Brambilla; Sylvie Gazzeri; V. Gouyer; D. Moro; A. Negoescu; C. Brambilla

Neuroendocrine (NE) lung tumors encompass a spectrum from typical and typical carcinoids representing low and intermediate grade tumors respectively and high grade tumors represented by large cell neuroendocrine tumors (LCNEC) [l] and small cell lung carcinoma (SCLC). This may reflect different levels of molecular abnormalities on the scale of genetic lesions giving rise to tumor growth. NE lung tumor spectrum provides a unique opportunity to compare molecular abnormalities between tumors of different grade sharing a common (NE) phenotype. Since tumor growth is the net result of proliferation and cell death, we have studied some of the factors which promote proliferation and decrease cell death (apoptosis). Acceleration of proliferation is the result of both gain of function of proteins encoding growth factors and oncogenes and loss of function of tumor suppressor gene encoded proteins, which normally exerce a negative control on growth signals transmitted by the first category of proteins. Escape from cell death is also partially related to tumor suppressor gene inactivation. We have studied the contribution of some tumor suppressor gene (P53, Rb, Pi 6) inactivation to the malignant potential of NE lung tumors. P53 and Rb, on a common pathway, regulate Gl arrest in case of DNA damage. On a Rb independent pathway, P53 also plays a role in apoptosis. P53 can be viewed as a sensor of genotoxic stress and tumor proliferation of cells with DNA damage. Rb itself is regulated at the level of its phosphorylation, by cyclin-dependent-kinases (CDK), themselves regulated by CDK-Inhibitors (CDK-I). We have studied the two types of Rb inactivation, in NE lung tumors: the direct way which involves the absence of Rb protein expression, and the indirect pathway by which Rb phosphorylation is deregulated: this can be achieved by cyclin Dl overexpression or CDK-I (P16, P1.5) loss of expression. P53 inactivation in NE tumors can be reflected by stabilization of the P53 protein leading to P53 immunohistochemical (IH) detection [2]. P53 stabilization is commonly due to missense mutation, whereas minor types of mutation (20%) are not stabilizing, affect mRNA splicing sites, or create stop codons which interdict protein expression (null P53 phenotype), and generate negative P53 IH phenotype [3] P53 mutation and stabilization are well delineated along the NE lung tumor spectrum. Neither mutations nor P53 positive phenotype (IH) occur in typical carcinoid (TC), although we have observed null phenotype. Atypical carcinoid (AC) despite a low level P53 staining (20%), retain a wi P53 [4]. In contrast, LCNEC and SCLC display a 80% rate of P53 mutation: (from 50-80% using IH, and/or sequence analysis). Thus there is a significant increase in P53 mutation rate between carcinoids (TC + AC) and high grade NE tumors (LCNEC and SCLC) (p = 0.0003) [5]. Rb gene inactivation through absence of Rb protein expression occurs with a significantly increasing rate from TC (20%) to SCLC (80%). We found that absence of transcription was responsible for most of Rb “silencing” (SO%), whereas only 20% was due to mutation within Rb gene sequence [6]. The vast majority of cases which had retaind Rb expression had achieved Rb inactivation through CDK-I (P16) inhibition. Thus, there was an inverse correlation between Rb and P16 expressions in high grade NE lung tumors, SCLC and LCNEC (p = 0.0002). Only TC displayed a constant Rb+, P16+ genophenotype, showing that low grade NE tumors have retained Rb expression and the control of its phosphorylation. LCNEC differ from SCLC by a less drastic Rb loss, compensated by a highest rate of P16-P15 inactivation (very uncommon in NSCLC). Two dominant interacting proteins Bax and Bcl2 regulate the cell susceptibility to death in NE cells, and are under the transcriptional control of P53. There is a striking inverse relationship between bax and bcl2 at the level of individual tumors, and between low grade carcinoids and high grade LCNEC and SCLC. Along the NE lung tumors spectrum, increasing rate and level of bcl2 expression are paralleled by a decreasing rate and level of bax expression. This inverse relation crosses the spectrum at the level of AC. Interestingly, there is a strong relationship between high bax expression, low bcl2 expression and bax:bcl2 ratio more than unit, with prolonged survival in NE (excepted SCLC) across histological groups p < 0.002) [5]. This relation between bax:bcl2 ratio and survival has been confirmed in a large series of AC. Bcl2 increases in post-therapy samples of SCLC following other phenotypical traits of chemoresistant SCLC [7]. The highest levels of bc12 expression and bcl2:bax ratio are associated with P53 mutant immunophenotype (p = 0.02). Whereas P53 mutant phenotype was not related to prognosis in our study, bax and bcl2 balance appears to be the most significant factor for survival prediction in NE lung tumors. This emphasizes the differentiation specificity of bcl2 family proteins which have a weak prognostic value if any in NSCLC. In conclusion, genetic and molecular abnormalities in NE lung tumors confirm the concept of a continuous spectrum of malignancies from TC with no P53 mutation (no smoking habits), a low rate of Rb loss, no CDK-I (P16-P15) inactivation, and a low bcl2:bax ratio, to the high grade LCNEC, SCLC, with high rates of P53 mutation, and Rb loss, and a high bcl2:bax ratio. AC occupy an intermediate grade on the scale of molecular abnormalities. LCNEC is a specific tumor type with severe genetic lesions, differing from SCLC by a lower rate of Rb loss, compensated by a drastic P16-P15 inactivation. The molecular characteristics of NE lung tumors indicate potential therapeutic targets that could ideally “convince” SCLC or LCNEC tumor cells to mimic carcinoid cells. Bax gene transfert, bc12 attenuation, Rb or P16 gene transfer or modulation, might provide therapeutic approaches according to specific molecular pathology status.


Clinical Cancer Research | 1998

p53 mutant immunophenotype and deregulation of p53 transcription pathway (Bcl2, Bax, and Waf1) in precursor bronchial lesions of lung cancer.

E. Brambilla; Sylvie Gazzeri; Sylvie Lantuejoul; Jean-Luc Coll; Denis Moro; Negoescu A; C. Brambilla


Chest | 2002

Cigarette Smoking, Preinvasive Bronchial Lesions, and Autofluorescence Bronchoscopy*

D. Moro-Sibilot; Michel Jeanmart; Sylvie Lantuejoul; François Arbib; Marie Hélène Laverriére; Elizabeth Brambilla; C. Brambilla


Lung Cancer | 2005

O-169 Prognostic significance of carcinoma in situ in the vicinity ofnon small cell resected lung cancer in stage I to IIIA

A. Aubert; Denis Moro-Sibilot; S. Diab; G. Riehl; Sylvie Lantuejoul; E. Brambilla; P. Brichon; C. Brambilla


Lung Cancer | 2005

O-128 Carcinoma with basaloid features: A histopathological entity ofpoor prognosis

S. Diab; Denis Moro-Sibilot; Sylvie Lantuejoul; A. Aubert; E. Hodaj; E. Brambilla; C. Brambilla; P. Brichon


Lung Cancer | 1997

668 Differential expression and prognosis value of neural cell adhesion molecules (NCAM) and polysialylated-NCAM (NCAM-PSA) in neuroendocrine lung tumors

Sylvie Lantuejoul; Denis Moro; A. Negoescu; C. Brambilla; E. Brambilla


Lung Cancer | 1997

693 Neural cell adhesion molecules (NCAM) expression in malignant mesothelioma

Sylvie Lantuejoul; H. Sartelet; P.Y. Brichon; C. Brambilla; E. Brambilla

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Denis Moro

Joseph Fourier University

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D. Moro-Sibilot

Centre Hospitalier Universitaire de Grenoble

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Elizabeth Brambilla

Centre Hospitalier Universitaire de Grenoble

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Anne-Claire Toffart

Centre Hospitalier Universitaire de Grenoble

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François Arbib

French Institute of Health and Medical Research

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Gilles Devouassoux

Centre Hospitalier Universitaire de Grenoble

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Hélène Mignotte

Centre Hospitalier Universitaire de Grenoble

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I Ziany-bey

Centre Hospitalier Universitaire de Grenoble

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Marie Hélène Laverriére

Centre Hospitalier Universitaire de Grenoble

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