Boukari F.,Service Route |
Butori C.,Laboratoire Of Pathologie Clinique Et Experimentale |
Cardot-Leccia N.,Laboratoire Central dAnatomie Pathologique |
David S.,Service de Chirurgie Reparatrice et Reconstructrice et Esthetique |
And 2 more authors.
Annales de Dermatologie et de Venereologie | Year: 2014
Background Histiocytoma (HC) is a very common benign tumour generally seen in the lower limbs of adults, particularly women. There are, however, atypical forms of HC that behave like locally aggressive tumours, occasionally with relapse or even metastasis. Herein we report a case of locally aggressive HC in a child, which, on account of its clinical extension, required seven surgical procedures to achieve complete excision. Patients and methods A 13-year-old child consulted for a hard purplish papule measuring 8 mm in diameter located in the right lumbar region. Punch biopsy revealed a poorly delineated dermal-hypodermic tumour comprising randomly distributed moderately pleomorphic fusiform cells, arranged in bands or with storiform architecture, certain of which were multi-nucleated. The mitotic index was high (11 mitoses in 10 fields at high magnification). There was no expression by the tumour of melanocytic markers (PS100, Melan-A), histiocytic markers (CD68) or CD34. FISH analysis showed the absence of COL1A1-PDGFB fusion gene. Based on these immunohistochemical and molecular findings, a diagnosis was made of atypical HC with high cellular density. Since the lower margins of the section showed tumoural foci, surgical excision was performed with 5-mm margins. Because the lateral and vertical limits were reached in all cases, a series of five further procedures (the last of was preceded by multiple peripheral biopsies) was necessary to achieve complete excision. These multiple excision procedures resulted in total excision of 25 cm across the longest side. No clinical relapse was seen after 25 months. Discussion Cellular or atypical forms of HC carry a high likelihood of post-surgical relapse. They are characterised by marked pleomorphism and high cellular density. In our patient, the extent of the lesion had been greatly underestimated initially, resulting in the need for several surgical procedures in order to achieve complete excision. It is thus important to highlight the predictive factors for this type of tumour in order to enable sufficiently extensive excision, or excision guided by previous biopsies, to be contemplated from the outset. These predictive factors are: young patient age, unusual location (trunk, face, neck), high cellularity, marked mitotic activity and deep extension. © 2014 Elsevier Masson SAS. Tous droits reserves.
Meric R.,Nice University Hospital Center |
Maurel F.,Nice University Hospital Center |
Grangeon C.,Nice University Hospital Center |
Koulibaly M.,Nice University Hospital Center |
And 9 more authors.
Medecine Nucleaire | Year: 2012
Introduction/objectives: Tumoural cells develop an accelerated glycolytic metabolism for their development. Thus cancer cells have to maintain a greater glucose supply and to correct for the massive acidosis that produces glucose degradation in lactic acid at the same time. The increase of glucose transport can be estimated in vivo by positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose ( 18F-FDG). The carbonic anhydrase IX (CAIX), an enzyme overexpressed to fight against acidosis, can be estimated ex-vivo by immunohistochemistry. The purpose of this work is to study the expression of the CAIX and the 18F-FDG uptake in primitive non small cells lung cancers (NSCLC). Material and methods: One hundred and seven patients of the Centre Hospitalier Universitaire de Nice (CHUN, Teaching Hospital of Nice) with NSCLC surgically treated in the thoracic surgery department, having been tested for the expression of the CAIX in the department of clinical and experimental pathology, and having benefited from a PET scan with 18F-FDG in the department of nuclear medicine of the CHUN, were retrospectively included from a cohort of 555 patients. The intensity of tumoural 18F-FDG uptake was measured by 16 different methods, with in particular the calculation of "tumour on background" ratios of uptake and of values corrected from partial volume effect (PVE). This correction was made possible by calibration experiments on phantoms by the recovery coefficient method. Results: A significative correlation between the expression of the CAIX and "maximum tumoural uptake on liver background" ratio was found. Discussion: High CAIX and SUV are known to be independent factors of poor prognosis for patients suffering from NSCLC. The 18F-FDG uptake reflects the expression of the glucose transporter GLUT, which is strongly increased in most of the malignant tumours. Even on modern PET devices, PVE remains an important quantitative bias in emission imaging, by provoking important underestimates of small structures uptake. Its correction appreciably improves the precision of quantification in PET imaging. At the molecular level, the transcription factor Hypoxia-Inducible Factor (HIF-1α) is the keystone of activation of numerous genes producing in particular the GLUTs, key enzymes of glycolysis and the CAIX. Thus a metabolic link is expected and found between 18F-FDG uptake and the CAIX expression via HIF-1α, what was shown in a single study carried out on a low number of patients and without PVE correction. Conclusion: The correlation suggested here between 18F-FDG uptake and expression of the CAIX seems to be in agreement with the biological hypothesis. Other studies remain necessary to show that PET with 18F-FDG, associated with the test of the tumoral expression of the CAIX, would allow refining the prognosis of these patients and estimating the prediction of the response to anti-cancerous therapies. © 2012 Elsevier Masson SAS.
Hofman V.,Laboratoire Of Pathologie Clinique Et Experimentale |
Hofman V.,Sophia University |
Long E.,Laboratoire Of Pathologie Clinique Et Experimentale |
Long E.,Sophia University |
And 5 more authors.
Revue Francophone des Laboratoires | Year: 2013
For several decades, there is a strong and permanent effort in translational research for the discovery of new oncology biomarker for diagnosis (in particular for an early screening of cancer), prognosis or prediction of treatment efficacy. These biomarkers are analyzed from tissues, cells or biological fluid samples. In this context, there is a growing enthusiasm around the detection of circulating tumor cells (CTC) in the blood of cancer patients since this detection may have a strong diagnostic, prognostic and/or theranostic interest. Numerous direct and indirect methods were developed to detect and characterize the CTC. However, there is a great variability in the sensitivity and the specificity of these methods. Each available method shows certain advantages, but also some disadvantages. The advent of targeted therapies in oncology has suddenly intensified the interest in the CTC field. The detection of genomic alterations in CTC could be associated with a personalized medicine according to the identified mutations. The purpose of this review is to describe the main methods for CTC detection and characterization, and the potential clinical utility of CTC in oncology. © 2013 - Elsevier Masson SAS - Tous droits réservés.
Guibert N.,University Paul Sabatier |
Ilie M.,Laboratoire Of Pathologie Clinique Et Experimentale |
Lena H.,Rennes University Hospital Center |
Didier A.,University Paul Sabatier |
And 2 more authors.
Revue des Maladies Respiratoires | Year: 2016
A better understanding of oncogenesis and the development of targeted therapieshave led to improved outcomes in the treatment of lung cancer. KRAS mutation has the potentialto drive the oncogenesis of almost one third of lung adenocarcinomas but it leads to a highlycomplex proliferation signal involving multiple signaling pathways, explaining the disappointingresults of various inhibition strategies of K-ras or its effectors. Nevertheless, recent data suggestdifferent roles of distinct KRAS mutation subtypes and KRAS interactions with new genes in thefield of synthetic lethality mechanisms open the way to new therapeutic possibilities. Thisreview aims to provide an overview of: 1) epidemiological data and particularly the prognosticimpact of KRAS mutations in non-small cell lung cancer, 2) the results of different drugs eitherbeing tested in humans or sources of hope. © 2015 Published by Elsevier Masson SAS on behalf of SPLF.
Hofman P.,Laboratoire Of Pathologie Clinique Et Experimentale
Revue des Maladies Respiratoires Actualites | Year: 2011
The increase number of methods to be perform from various biospecimens in thoracic oncology field raises the following question: How to set up a new strategy for the best handling of tissular and cellular samples. The diagnosis, but also the prognosis and the theragnosis of lung cancer have to be made by the pathologist from biological samples of smaller and smaller size. In this regard, the management of those specimens have to be think in a new way in the pathology laboratory, according to different expertises. Even though the morphological evaluation must be in all cases the key for the diagnosis, the number of immunohistochemical and in situ hybridization studies to be performed has to be evaluated in the same time, since the material could be rare. Moreover, it is necessary to think in parallel about the search of an increased number of mutations, in particular from DNA of quality. Finally, the integration of new biopathology approaches, such as the detection of peripheral biomarkers obtained from blood samples, as the detection of circulating tumour cells, should be also evaluated soon. © 2011 Société de Pneumologie de Langue Française (SPLF).
Guibert N.,French Institute of Health and Medical Research |
Ilie M.,French Institute of Health and Medical Research |
Ilie M.,Laboratoire Of Pathologie Clinique Et Experimentale |
Long E.,French Institute of Health and Medical Research |
And 11 more authors.
Current Molecular Medicine | Year: 2015
KRAS mutations are detected in over one third of lung adenocarcinomas, most frequently in Caucasian and smoker patients. The impact of KRAS mutations on lung adenocarcinoma prognosis is currently subject to debate, as is their impact on the response to chemotherapy and EGFR tyrosine kinase inhibitors. The different methods for KRAS status assessment, based on histological and cytological samples or biological fluids, offer varying sensitivities. Since no treatments are available in clinical routine for KRAS-mutated lung cancer patients, one of the current major challenges in thoracic oncology is developing new dedicated strategic therapies. Different molecules can be developed that act on a post-transcriptional KRAS protein level, blocking its cytoplasmic membrane recruitment. The efficacy of these molecules' targeting of the different signaling pathways activated by the KRAS mutation (such as the MEK and BRAF pathways) is related to the particular KRAS mutation subtype. New therapeutic strategies are currently focused on certain genes linked with KRAS inducing a synthetic lethal interaction. The purpose of this work is to provide an overview of i) the recent epidemiological and molecular findings concerning KRAS-mutated lung adenocarcinoma, ii) the prognostic impact of KRAS mutations, in particular during response to treatment, iii) the available methods for detecting this mutation, and iv) the current molecules under development for new therapeutic strategies and the clinical trials targeting this genomic alteration. © 2015 Bentham Science Publishers.
PubMed | Laboratoire Of Pathologie Clinique Et Experimentale, University Paul Sabatier and Rennes University Hospital Center
Type: Journal Article | Journal: Revue des maladies respiratoires | Year: 2016
A better understanding of oncogenesis and the development of targeted therapies have led to improved outcomes in the treatment of lung cancer. KRAS mutation has the potential to drive the oncogenesis of almost one third of lung adenocarcinomas but it leads to a highly complex proliferation signal involving multiple signaling pathways, explaining the disappointing results of various inhibition strategies of K-ras or its effectors. Nevertheless, recent data suggest different roles of distinct KRAS mutation subtypes and KRAS interactions with new genes in the field of synthetic lethality mechanisms open the way to new therapeutic possibilities. This review aims to provide an overview of: 1) epidemiological data and particularly the prognostic impact of KRAS mutations in non-small cell lung cancer, 2) the results of different drugs either being tested in humans or sources of hope.