Publications (29)98.05 Total impact
-
Article: High Incidence of Triple-Negative Tumors in Sub-Saharan Africa: A Prospective Study of Breast Cancer Characteristics and Risk Factors in Malian Women Seen in a Bamako University Hospital.
[show abstract] [hide abstract]
ABSTRACT: Objective: Few studies have been conducted on breast cancer in Sub-Saharan Africa and their results have been suspected to be impaired by artefacts. This prospective study was designed to determine tumor and patient characteristics in Mali with control of each methodological step. These data are necessary to define breast cancer treatment guidelines in this country. Methods: Clinical and tumor characteristics and known risk factors were obtained in a consecutive series of 114 patients. Each technical step for the determination of tumor characteristics [histology, TNM, grade, estrogen (ER) and progesterone receptors (PR), HER2, and Ki67] was controlled. Results: Patients had a mean age of 46 years. Most tumors were invasive ductal carcinomas (94%), T3-T4 (90%) with positive nodes (91%), grade III (78%), and ER (61%) and PR (72%) negative. HER2 was overexpressed in 18% of cases. The triple-negative subgroup represented 46%, displaying a particularly aggressive pattern (90% grade III; 88% Ki67 >20%). Conclusion: This study demonstrates the high incidence of aggressive triple-negative tumors in Mali. Apart from a higher prevalence of premenopausal women, no significant difference in risk factors was observed between triple-negative tumors and other tumors. The hormonal therapy systematically prescribed therefore needs to be revised in light of this study.Oncology 09/2012; 83(5):257-263. · 2.27 Impact Factor -
Article: Eutopic endometrium and peritoneal, ovarian and colorectal endometriotic tissues express a different profile of Nectin-1, -3, -4 and nectin-like molecule 2.
[show abstract] [hide abstract]
ABSTRACT: How is the expression of nectins and nectin-like molecules (Necls) detected by immunostaining altered by endometriosis? SUMMARY ANSWER: Our results suggest that Nectin-1, -3, -4 and Necl-2 may contribute to the pathogenesis of endometriosis. Immunostaining of nectins and Necls varies according to the anatomical location of endometriosis. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Nectin and Necl molecules are immunoglobulin-like cell adhesion molecules involved in apoptosis, cell proliferation and in metastases. Previous studies have demonstrated the involvement of adhesion molecules in the development of endometriotic lesions but no data exist on immunostaining of nectins and Necls molecules in endometriosis. This retrospective study was conducted in a tertiary-care hospital (Tenon Hospital, Paris, France). Samples were collected from 55 women undergoing endometrial biopsy or surgery for endometriosis and 20 controls having hysterectomy or endometrial biopsy for other reasons; multiple samples were collected from 15 women. We studied the immunostaining of Nectin-1, -3, -4 and Necl-2 in secretory and proliferative endometrium from women with (n = 20) or without endometriosis (i.e. control group, n = 20), and in peritoneal (n = 20), ovarian (n = 20) and colorectal endometriosis (n = 20). Semi-quantitative immunostaining demonstrated that (1) Necl-2 staining was stronger in all types of endometriotic lesions than in the eutopic endometrium from patients with endometriosis (P < 0.0125) and in ovarian endometriotic cysts compared with other locations (P < 0.001); (2) Nectin-3 staining was stronger in the eutopic endometrium of patients with endometriosis compared with controls (P = 0.03) and in all endometriotic lesions compared with the eutopic endometrium from patients with endometriosis (P < 0.0125); (3) Nectin-4, staining was stronger in the eutopic endometrium of patients with endometriosis compared with controls (P = 0.04) and (4) Nectin-1 staining was significantly increased in colorectal endometriosis compared with other locations (P = 0.004). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: We did not assess the pattern of expression in endometriosis of all nectins and Necl molecules. Indeed, Necl-5 is implicated in many pathophysiological processes such as cell movement and proliferation with potential relevance to endometriosis. GENERALISABILITY TO OTHER POPULATIONS: At present, few data on implication of nectins and Necl molecules in endometriosis exist. Hence, our results should be confirmed by further quantitative studies at protein or RNA levels. STUDY FUNDING/COMPETING INTEREST(S): No funding source. All the authors declare no conflict of interest.Human Reproduction 08/2012; 27(11):3179-86. · 4.47 Impact Factor -
Article: Lymph node metastasis as a new target for cancer treatment
[show abstract] [hide abstract]
ABSTRACT: The presence of lymph node metastasis is predictive of poor prognosis in solid tumors. Demonstration of specific markers of lymphatic endothelial cells has facilitated the study of the molecular mechanisms of metastasis, particularly lymphangiogenesis. The vascular endothelial growth factor (VEGF)-C/VEGF-D/VEGF receptor (VEGFR)-3 axis has been the most extensively studied, but other molecular pathways are also involved, such as fibroblast growth factor (FGF)-2, platelet-derived growth factor (PDGF)-BB, angiopoietin-1, VEGF-A, hepatocyte growth factor (HGF), insulin-like growth factor (IGF)-1 and -1R, and cyclooxygenase-2. Several strategies are currently being developed to prevent lymphatic metastasis, mainly targeting the VEGF-C/VEGF-D/VEGFR-3 axis: inhibiting maturation and activation of VEGF-C and VEGF-D by successive proteolyses, inhibiting binding of ligands to their receptor, and using tyrosine kinase inhibitors. Many questions remain and will be discussed in this article, particularly the role of lymph node metastasis in the development of visceral metastases, possible toxicities of antilymphangiogenic treatments, and their possible interactions with intratumoral penetration of other anticancer agents.Targeted Oncology 04/2012; 2(1):49-57. · 0.46 Impact Factor -
Article: Multigene mutation analysis on cytologic samples.
Chest 12/2011; 140(6):1664; author reply 1664-5. · 5.25 Impact Factor -
Article: Tissue factor over-expression by human pancreatic cancer cells BXPC3 is related to higher prothrombotic potential as compared to breast cancer cells MCF7.
[show abstract] [hide abstract]
ABSTRACT: Cancer histology influences the risk of venous thromboembolism and tissue factor (TF) is the key molecule in cancer-induced hypercoagulability. We investigated the relation between TF expression by pancreatic and breast cancer cells (BXPC3 and MCF7 respectively) and their capacity to trigger in vitro thrombin generation in normal human plasma. Flow cytometry and Western blot analysis for TF expression were performed using murine IgG1 monoclonal antibody against human TF. Real-time PCR for TFmRNA was also performed. Activity of TF expressed by cancer cells was measured with a specific chromogenic assay. Thrombin generation in PPP was assessed using calibrated automated thrombogram. Cancer cells were added to platelet poor plasma from healthy volunteers. In separate experiments cells were incubated with the anti-TF antibody at concentration that completely neutralized the activity of recombinant human TF on thrombin generation. BXPC3 cells expressed significantly higher amounts of functional TF as compared to MCF7 cells. Incubation of BXPC3 and MCF7 cells with PPP resulted in acceleration of the initiation phase of thrombin generation. BXPC3 cells manifested higher procoagulant potential than MCF7 cells. The incubation of BXPC3 or MCF7 cells with the anti-TF monoclonal antibody which resulted in reversal of their effect on thrombin generation. The present study establishes a link between the amount of TF expressed by cancer cells with their procoagulant activity. Both studied types of cancer cells trigger thrombin generation but they have different procoagulant potential. The procoagulant activity of BXPC3 and MCF7 cells is related to the amount of TF expressed. Kinetic parameters of thrombogram are the most relevant for the detection of the TF-dependent procoagulant activity of cancer cells. TF expression is one of the mechanisms by which cancer cells manifest their procoagulant potential but it is not the unique one. The present experimental model will allow the characterization the procoagulant fingerprint of cell lines from the same or different histological types of cancer.Thrombosis Research 09/2011; 129(6):779-86. · 2.44 Impact Factor -
Article: [Breast cancer in Sub-Saharan African women: review].
[show abstract] [hide abstract]
ABSTRACT: Breast cancer is the second most frequent cancer in Sub-Saharan African women with an incidence of 15-53 per 100,000 women. Using PubMed, we reviewed all the articles published on this topic between 1989 and 2009. Breast cancer is usually diagnosed in women younger than in developed countries (mean age: 42-53 years), with later stages (III or IV, i.e. with axillary nodes and distant metastases). Reported tumors are mostly invasive ductal carcinomas with aggressive characteristics: grade III histoprognosis, absence of hormonal receptors or HER2 expression. According to the new breast cancer classification, nearly half of these tumors should be classified as triple negative. However, studies are rare and require confirmation. In conclusion, data on epidemiology and biology of breast cancer in Sub-Saharan African women are still scarce and need more extensive studies. In these countries, the pattern of breast cancer will likely change in the future, according to the evolution of lifestyle namely urbanisation. There is a great need for commitment of research and clinical resources in Sub-Saharan Africa in order to develop specific strategies.Bulletin du cancer 06/2011; 98(7):797-806. · 0.67 Impact Factor -
Article: [Are centrosomal abnormalities correlated to DNA ploidy in breast cancer?].
[show abstract] [hide abstract]
ABSTRACT: ADN ploidy was shown to play a role in genomic instability of cancer cells and prognosis. The implication of the centrosome in the cell cycle was also described. Therefore, new prognostic factors could be suggested for a better-tailored therapy. The purpose of this study is to search for correlation between centrosomal abnormality and ADN ploidy in breast cancer. Cell prints were prepared from cell culture of mesothelial ascitis, fibroblast cell line MRC5 and breast cancer cell lines MCF7 and T47D. Fresh cell prints were also obtained from cases with invasive carcinoma. The centrosome was labelled by an indirect immunofluorescence assay using anti-γ-tubulin antibody and F(ab')(2) FITC before quantification with fluorescence microscopy. ADN ploidy was scored with DNA index obtained by means of flux cytometry. The normal mesothelial cells (94% of cells with only one centrosome) and the diploid cell line MRC5 (68% of cells with two centrosomes) were used as controls. DNA ploidy was found to be correlated with centrosomal abnormality in MCF7 cell line (64% of cells had more than three centrosomes) but not in the 10 cases of invasive ductal carcinoma analysed in this study. The absence of correlation between DNA ploidy and centrosomal abnormality in breast cancer samples may be due to the small numbers of cases, the cell prints or tumorigenesis. Correlation analysis of a larger number of cases and types of breast lesions to numerical and morphological abnormalities of the centrosome are ongoing.Annales de biologie clinique 04/2011; 69(2):181-9. · 0.34 Impact Factor -
Article: Release of metal particles from needles used for transbronchial needle aspiration.
[show abstract] [hide abstract]
ABSTRACT: Although mediastinoscopy is still the gold standard for diagnosis of mediastinal lymphadenopathy, minimally invasive procedures have been developed: transbronchial needle aspiration (TBNA) using a flexible bronchoscope (conventional TBNA) or linear echoendoscope (endobronchial ultrasound [EBUS]) allowing real-time guided lymph node aspiration. The observation of contamination of samples by foreign particles led us to determine the frequency and the nature of this material and to identify its origin. From June 2007 to November 2008, 141 consecutive patients underwent conventional TBNA (n = 84) or EBUS-guided TBNA (EBUS-TBNA) (n = 57). All cytologic samples were reviewed in blinded fashion, and contamination was assessed semiquantitatively. Mineral analysis using a transmission electron microscope equipped with an energy dispersive x-ray spectrometer was performed on the solution obtained after rinsing unused needles and on four samples of calf thymuses punctured with EBUS needles. Foreign material, different from anthracosis, was identified in samples obtained with five different batches of needles, only from EBUS-TBNA (P < .0001). The contamination score was correlated to the number of passes (P = .035). Mineral analyses of the rinsing solutions from conventional TBNA needles were negative, whereas metal alloys of iron, titanium, nickel, and chromium were released with EBUS needles. The same contamination was identified in three of the four punctured calf thymuses. Dedicated EBUS-TBNA needles are able to release metal particles, probably by friction between the stylet and the needle, with a potential risk to inject particles into nodes. The long-term consequences are unknown, but the need for safety measures should be evaluated.Chest 01/2011; 139(1):138-43. · 5.25 Impact Factor -
Article: Are adenosquamous lung carcinomas a simple mix of adenocarcinomas and squamous cell carcinomas, or more complex at the molecular level?
[show abstract] [hide abstract]
ABSTRACT: Adenocarcinomas (AC), squamous cell carcinomas (SCC) and adenosquamous carcinomas (ASC) are three histological subtypes of non-small-cell lung carcinomas (NSCLC). ASC are morphologically mixed tumours that contain the two cell components AC and SCC. To understand if they are a "simple" mix of AC and SCC or if they present molecular specificities, as compared with the molecular characterization of both components, we performed a comparative transcriptome analysis on a series of nine ASC, five AC and five SCC induced in rats by radon exposure. We found that 72, 40 and 39 genes were differentially expressed when comparing AC_SCC, ASC_SCC and AC_ASC, respectively. Moreover, when classifying the three histological subtypes, using genes that discriminated AC and SCC, we observed that all ASC were classified as intermediate between the AC and SCC, some being closer to AC, others to SCC. These results indicated that, regarding gene expression, ASC could be considered as a mix of AC and SCC, both in various proportions. However, they also exhibit molecular specificities since we found specific genes discriminating ASC_SCC and AC_ASC. In conclusion, the ASC mixed lung tumours are more complex than simple mixes of AC and SCC components. Neuroendocrine differentiation and ERK proliferation pathways seemed preferentially deregulated in ASC compared to AC and SCC respectively, pathways that are worthy of being explored because they could partially explain the high clinical aggressiveness of ASC.Lung cancer (Amsterdam, Netherlands) 12/2009; 68(1):1-9. · 3.14 Impact Factor -
Article: Intralobular pulmonary lymphatic distribution in normal human lung using D2-40 antipodoplanin immunostaining.
[show abstract] [hide abstract]
ABSTRACT: It has been assumed for a long time that except for limited areas close to respiratory bronchioles or their satellite arteries, there is no evidence of lymphatic vessels deep in the pulmonary lobule. An immunohistochemical study using the D2-40 monoclonal antibody was performed on normal pulmonary samples obtained from surgical specimens, with particular attention to the intralobular distribution of lymphatic vessels. This study demonstrated the presence of lymphatics not only in the connective tissue surrounding the respiratory bronchioles but also associated with intralobular arterioles and/or small veins even less than 50 mum in diameter. A few interlobular lymphatic vessels with a diameter ranging from 10 mum to 20 mum were also observed further away, in interalveolar walls. In conclusion, this study, using the D2-40 monoclonal antibody, demonstrated the presence of small lymphatic channels within the normal human pulmonary lobules, emerging from interalveolar interstitium, and around small blood vessels constituting the paraalveolar lymphatics. This thin intralobular lymphatic network may play a key pathophysiological role in a wide variety of alveolar and interstitial lung diseases and requires further investigation.Journal of Histochemistry and Cytochemistry 04/2009; 57(7):643-8. · 2.72 Impact Factor -
Article: Molecular analysis of the Ink4a/Rb1-Arf/Tp53 pathways in radon-induced rat lung tumors.
[show abstract] [hide abstract]
ABSTRACT: Inhalation of radon is closely associated with an increased risk of lung cancers. While the involvement of Ink4a in lung tumor development has been widely described, the tumor suppressor gene has not been studied in radon-induced lung tumors. In this study, loss of heterozygosity (LOH) analysis of the Cdkn2a locus, common to the Ink4a and Arf genes, was performed on 33 radon-induced rat lung tumors and showed a DNA loss in 50% of cases. The analysis of p16(Ink4a) protein expression by immunohistochemistry revealed that 50% of the tumors were negative for this protein. Looking for the origin of this lack of expression, we observed a low frequency of homozygous deletion (6%), a lack of mutation, an absence of correlation between promoter methylation and Ink4a mRNA expression and no correlation between LOH and protein expression. However, a tendency for an inverse correlation between p16(Ink4a) and pRb protein expression was observed. The expressions of p19Arf, Mmd2 and Mdm4 were not deregulated and only 14% of the tumors were mutated for Tp53. These results indicated that Ink4a/Cdk4/Rb1 pathway deregulation, more than Arf/Mdm2/Tp53 pathway, has a major role in the development of these tumors through p16(Ink4a) deregulation. However, all known mechanisms of inactivation of the pathway do not play a recurrent role in these tumors and the actual origin of the lack of p16(Ink4a) protein expression remains to be established.Lung Cancer 03/2009; 63(3):348-53. · 3.43 Impact Factor -
Article: Clinical significance of micrometastases detection in lymph nodes from head and neck squamous cell carcinoma.
[show abstract] [hide abstract]
ABSTRACT: Study the clinical relevance of micrometastases in head and neck squamous cell carcinoma (HNSCC). We reviewed the outcome of 31 patients who underwent neck dissection for HNSCC with lymph node analysis by cytokeratin 19 real-time Taqman polymerase chain reaction (CK19RT-PCR) for detection of micrometastasis. Fifteen patients were N+ on histopathology (group 1) and 16 were N-; nine of these 16 patients were CK19RT-PCR positive (group 2), whereas seven were negative (group 3). Local and neck recurrences, metastases, and other tumour sites were recorded during follow-up. Five patients in group 1, eight patients in group 2, and one patient in group 3 experienced a tumor-related event. N- patients in groups 2 and 3 had a different outcome (P<0.01). It is suggested that CK19RTPCR detection of micrometastasis in lymph nodes could be of significant prognostic value in HNSCC, because more aggressive treatment could be indicated in these patients.Otolaryngology Head and Neck Surgery 10/2008; 139(3):436-41. · 1.72 Impact Factor -
Article: Individual risk prediction of nodal and distant metastasis for patients with typical bronchial carcinoid tumors.
[show abstract] [hide abstract]
ABSTRACT: Bronchial typical carcinoid tumors are low-grade malignancies. However, metastases are diagnosed in some patients. Predicting the individual risk of these metastases to determine patients eligible for a radical lymphadenectomy and patients to be followed-up because of distant metastasis risk is relevant. Our objective was to screen for predictive criteria of bronchial typical carcinoid tumor aggressiveness based on a logistic regression model using clinical, pathological and biomolecular data. A multicenter retrospective cohort study, including 330 consecutive patients operated on for bronchial typical carcinoid tumors and followed-up during a period more than 10 years in two university hospitals was performed. Selected data to predict the individual risk for both nodal and distant metastasis were: age, gender, TNM staging, tumor diameter and location (central/peripheral), tumor immunostaining index of p53 and Ki67, Bcl2 and the extracellular density of neoformed microvessels and of collagen/elastic extracellular fibers. Nodal and distant metastasis incidence was 11% and 5%, respectively. Univariate analysis identified all the studied biomarkers as related to nodal metastasis. Multivariate analysis identified a predictive variable for nodal metastasis: neo angiogenesis, quantified by the neoformed pathological microvessels density. Distant metastasis was related to male gender. Discussion: Predictive models based on clinical and biomolecular data could be used to predict individual risk for metastasis. Patients under a high individual risk for lymph node metastasis should be considered as candidates to mediastinal lymphadenectomy. Those under a high risk of distant metastasis should be followed-up as having an aggressive disease. Individual risk prediction of bronchial typical carcinoid tumor metastasis for patients operated on can be calculated in function of biomolecular data. Prediction models can detect high-risk patients and help surgeons to identify patients requiring radical lymphadenectomy and help oncologists to identify those as having an aggressive disease requiring prolonged follow-up.European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 10/2008; 34(3):473-7; discussion 477-8. · 2.40 Impact Factor -
Article: Congenital tracheal malformation in cystic fibrosis transmembrane conductance regulator-deficient mice.
[show abstract] [hide abstract]
ABSTRACT: In cystic fibrosis (CF) patients, the major alteration in pulmonary function is due to peripheral airway obstruction. In the present study, we investigated the possibility that alterations in the extrathoracic airways, particularly in the trachea that expresses high levels of CFTR (CF transmembrane conductance regulator), may contribute to respiratory dysfunction. We performed morphological analyses of the trachea and airway functional studies in adult Cftr knockout (Cftr(-/-)) and F508del-CFTR mice and their controls. Macroscopic and histological examination of the trachea showed the presence of one to seven disrupted or incomplete cartilage rings in Cftr(-/-) mice (23/25) while only a few Cftr(+/+) mice (6/25) had one abnormal ring. Tracheal defects were mainly localized in the proximal trachea. In 14 Cftr(-/-) mice, frontal disruption of the first three to six rings below the cricoid cartilage were associated with upper tracheal constriction. Similar tracheal abnormalities were detected in adult F508del-CFTR and in newborn Cftr(-/-) and F508del-CFTR mice. Tracheal and ventilatory function analyses showed in Cftr(-/-) mice a decreased contractile response of the proximal trachea and a reduced breathing rate due to an increase in the inspiratory and expiratory times. In F508del-CFTR mice, the expiratory time was longer than in controls. Therefore, these structural and functional abnormalities detected in adult and newborn CF mouse models may represent congenital malformations related to CFTR dysfunction. These results raise important questions concerning the mechanisms governing tracheal development within the context of CFTR protein dysfunction and the implication of such abnormalities in the pathogenesis of airway disease in CF.The Journal of Physiology 08/2008; 586(13):3231-43. · 4.72 Impact Factor -
Article: Computerized morphometric analysis of microvasculature in non-small cell lung carcinoma.
[show abstract] [hide abstract]
ABSTRACT: Interactions between tumor cells and microvasculature are particularly critical. This computerized morphometric study was designed to analyze the distance between cancer cells and blood vessels and microvasculature organization in non-small cell lung carcinoma (NSCLC) comparing squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Seventy nine nests of tumor cells, located less than or more than 3 mm from the invading edge, with a similar surface area, and their surrounding stroma were analyzed. After immunolabeling with an antihuman CD34 monoclonal antibody, computerized morphometric analyses of microvascular density (MVD), distribution of microvessels within stroma, and fractions of carcinomatous cells over various distances from microvessels were performed. This analysis showed a significantly higher MVD score in ADC than in SCC, particularly close to the invading edge (382+/-57 in ADC <3 mm; 242+/-28 in SCC <3 mm, p=0.015). Moreover, a significantly higher proportion of cancer cells was situated more than 75 microm from microvessels in SCC than in ADC, regardless of their site in relation to the invading edge (for example, 25+/-5% in ADC <3 mm; 52+/-3% in SCC <3 mm, p=0.001).Microvascular Research 01/2008; 75(1):112-8. · 2.83 Impact Factor -
Article: Impact of nutrition on phenotype in CFTR-deficient mice.
[show abstract] [hide abstract]
ABSTRACT: To elucidate the impact of nutrition in cystic fibrosis (CF), we compared the phenotypic traits of Cftr -/- mice fed either a lipid-enriched liquid diet (Peptamen) or a standard chow combined with polyethylenglycol osmotic laxative (PEG), two strategies commonly used to prevent intestinal obstruction in CF mice. Survival, growth, liver, and ventilatory status were determined in Cftr -/- and Cftr +/+ mice, followed-up until 120 d. Ventilation was recorded in conscious animals using whole-body plethysmography. We found that the survival rate was similar in Peptamen and PEG Cftr -/- mice. Cftr -/- mice had lower minute ventilation than Cftr +/+ mice, whatever the diet. Both Cftr -/- and Cftr +/+ mice fed Peptamen displayed preadult growth delay compared with PEG-treated animals. Despite subsequent growth catch-up, Cftr -/- mice remained smaller than Cftr +/+ mice, whatever the diet. All Peptamen fed Cftr -/- mice showed hepatomegaly and liver steatosis, which also occurred but to a lesser extent in Peptamen fed Cftr +/+ animals. Therefore, while both treatment strategies are similarly efficient to avoid high mortality at weaning, Peptamen induces preadult growth delay and liver steatosis. These effects of diet are important to consider in future animal studies and also prompt to evaluate high-energy diets in CF patients.Pediatric Research 12/2007; 62(5):528-32. · 2.70 Impact Factor -
Article: Vascular endothelial growth factor-C and its receptor VEGFR-3 in non-small-cell lung cancer: concurrent expression in cancer cells from primary tumour and metastatic lymph node.
[show abstract] [hide abstract]
ABSTRACT: Investigation of the role of vascular endothelial growth factor-C (VEGF-C) and VEGF receptor-3 (VEGFR-3) in non-small-cell lung cancer (NSCLC) has mainly focused on lymph node (LN) metastasis related to lymphangiogenesis. However, the coexpression of VEGF-C/VEGFR-3 by tumour cells can independently play an important role. The present study was therefore designed to evaluate VEGF-C/VEGFR-3 coexpression in tumour cells from the primary tumour and corresponding LN metastases. VEGF-C and VEGFR-3 expression in cancer cells were evaluated by immunohistochemistry in 92 NSCLC samples and 45 metastatic LNs. Ki67 expression and mitotic index (MI) in tumours and clinicopathological data were analysed concurrently. VEGFR-3 and VEGF-C expression were observed in 42% and 74% of tumours, respectively. Concurrent expression of VEGF-C and VEGFR-3, observed in 39% of tumours, was significantly associated with a higher proliferation rate and a higher incidence of LN metastases. VEGF-C expression in tumour cells was observed in 100% of metastatic LN and VEGF-C/VEGFR-3 coexpression was observed in 71% of metastatic LN. Finally, concurrent expression of VEGF-C/VEGFR-3 in the primary tumour was associated with poor disease-free survival on univariate analysis. In NSCLC cancer cells, VEGF-C/VEGFR-3 coexpression suggests an autocrine/paracrine loop responsible for a high proliferation rate in tumour cells. As VEGF-C/VEGFR-3 coexpression is very frequent in metastatic LN tumour cells, it can be hypothesised that this coexpression participates in the growth of LN metastasis.Lung Cancer 12/2007; 58(2):205-13. · 3.43 Impact Factor -
Article: Immunolocalization and cell expression of lung resistance-related protein (LRP) in normal and tumoral human respiratory cells.
[show abstract] [hide abstract]
ABSTRACT: Lung resistance-related protein (LRP) is an integral part of the multidrug resistance (MDR) phenotype involved in cell resistance toward xenobiotics or chemotherapy. The aim of this study was to compare the intracellular localization and cell expression of LRP in normal bronchial cells and their tumoral counterparts from non-small cell lung cancer (NSCLC). LRP expression was also investigated concurrently with DNA ploidy and chromosome 16 (lrp gene locus) aberrations. Confocal microscopy showed that LRP localization was exclusively intracytoplasmic regardless of the cell type and was never observed in the nuclear pore complex. Flow cytometry demonstrated a similar level of LRP expression in normal bronchial cells and in cancer cells from NSCLC samples. FISH analysis, performed to evaluate the number of chromosome 16 and lrp loci, demonstrated a significant gain of chromosome 16 in DNA aneuploid tumors. Furthermore, we did not find any link between LRP expression and DNA ploidy status or chromosome 16 number. These results suggest that LRP expression observed in NSCLC, maintained through the carcinogenesis process of respiratory cells, is not altered by the increased number of copies of chromosome 16 and probably controlled by mechanisms different from those of MRP1 expression, whereas both proteins are associated with the MDR phenotype.Journal of Histochemistry and Cytochemistry 09/2007; 55(8):773-82. · 2.72 Impact Factor -
Article: Erythropoietin and erythropoietin receptor coexpression is associated with poor survival in stage I non-small cell lung cancer.
[show abstract] [hide abstract]
ABSTRACT: This study was designed to evaluate the prognostic effect of erythropoietin (EPO) and EPO receptor (EPO-R) expression in stage I non-small cell lung cancer (NSCLC) patients. EPO and EPO-R expression in 158 tumor samples from resected stage I NSCLC was evaluated using immunohistochemistry and tissue array technology. EPO-R and EPO were highly expressed in 20.9% and 35.4% of tumors, respectively. High EPO-R expression compared with negative or low-level expression was associated with a poor 5-year disease-specific survival (60.6% versus 80.8%; P = 0.01, log-rank test). High EPO expression compared with negative and low-level expression was associated with a trend toward a poor 5-year disease-specific survival (69.6% versus 80.4%; P = 0.13, log-rank test). A high level of EPO-R and EPO coexpression was associated with a poor 5-year disease-specific survival compared with other groups of patients (50.0% versus 80.0% survival at the end of follow-up; P = 0.005, log-rank test). In multivariate analysis for disease-specific survival, high-level EPO-R and EPO coexpression was an independent prognostic factor for disease-specific survival (hazard ratio, 2.214; 95% confidence interval, 1.012-4.848; P = 0.046). These results establish the pejorative prognostic value of EPO and EPO-R expression in early-stage resected NSCLC and suggest a potential paracrine and/or autocrine role of endogenous EPO in NSCLC aggressiveness.Clinical Cancer Research 09/2007; 13(16):4825-31. · 7.74 Impact Factor -
Article: Reappraisal of metastatic lymph node topography in head and neck squamous cell carcinomas.
[show abstract] [hide abstract]
ABSTRACT: To analyze the lymphatic distribution of metastatic carcinomatous cells in cervical lymph nodes in head and neck squamous cell carcinoma (HNSCC). We retrospectively reviewed 119 patients treated in our hospital for HNSCC (1999-2004). Topography of the neck dissection specimens was prospectively classified according to the classification of Robbins. The 4000 lymph nodes were analyzed by optical microscopy using hematoxylin-eosin-safran (HES) staining. In cases of negative results in level II, cytokeratin (AE1/AE3) immunodetection was performed. Metastases were visualized using HES in 6.4% of lymph nodes for oral cavity, and 4.7% of oropharyngeal, 4.4% of hypopharyngeal, and 1.3% of endolaryngeal cancers. The highest incidence of nodal metastasis was observed in level IIa (P < 0.01). In eight patients (6.7%) with lymph node metastases, level II was spared. In these patients, all 134 nodes histologically negative on HES were confirmed to be negative by IHC. Level IIa is the main level involved in regional metastases of HNSCC, regardless of the primary site of cancer. However, in eight (6.7%) patients, level II was spared, as confirmed by IHC. In these cases, level II did not represent the first step of drainage from the tumor. The sentinel lymph node technique in HNSCC is discussed in light of these results.Otolaryngology Head and Neck Surgery 09/2006; 135(3):445-50. · 1.72 Impact Factor
Top co-authors
Top Journals
Institutions
-
2012
-
Assistance Publique – Hôpitaux de Paris
Paris, Ile-de-France, France
-
-
2011
-
Hôpital Tenon – Hôpitaux universitaires Est Parisien
Paris, Ile-de-France, France
-
-
2002–2005
-
Université Pierre et Marie Curie Paris 6
Paris, Ile-de-France, France
-
