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Philippe Vielh

Publications and source records attributed to Philippe Vielh.

At least 19 recordsLinked to original sources
PubMed2007

Role of chemotherapy resistance genes in outcome of neuroblastoma.

BACKGROUND: Neuroblastoma is a heterogeneous pediatric disease. Most patients with localized disease usually have a favorable prognosis, but patients with advanced disease have a poor prognosis despite combination chemotherapy. Treatment failure may be attributable to resistance to cytotoxic drugs. PROCEDURE: Using quantitative RT-PCR, we investigated the clinical significance of the level of mRNA expression of multidrug resistance genes (MDR1, MRP1, MRP5, LRP) in a series of 29 advanced neuroblastoma samples. RESULTS: At the end of induction chemotherapy, 48% of patients achieved a clinical complete response, 28% achieved a partial response or stable disease, and 24% presented progressive disease. MDR1 mRNA overexpression (i.e., mRNA level >2 copies of MDR1 gene) was observed in 74% of samples, and MRP1, MRP5, LRP overexpression was observed less frequently (30, 33, and 33% of samples, respectively). None of these parameters were predictive of response, relapse, or survival. However, clinical response to treatment was highly predictive of relapse-free survival and overall survival. CONCLUSIONS: High expression of these multidrug resistance genes in advanced neuroblastoma is not the main parameter of response to cytotoxic drugs; clinical response to treatment remains the most important parameter in predicting the prognosis of patients with advanced neuroblastoma, until other relevant laboratory parameters have been identified.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Fine-needle aspiration cytology combined with flow cytometry immunophenotyping is a rapid and accurate approach for the evaluation of suspicious superficial lymphoid lesions.

The authors report a prospective study on 88 samples of superficial lesions (lymph nodes, skin nodules, and breast tumors), performed by fine-needle aspiration cytology (FNAC) in 74 patients, allowing (i) morphologic analysis combined with immunophenotyping by flow cytometry (FCM) and (ii) a cytogenetic study in 33 cases. Thirty-nine FNAC (44.3%) were performed at the time of diagnosis. The cytology results were correlated with histopathologic examination in 32 cases. Forty-nine FNAC (55.7%) were performed in the context of follow-up of a lymphoma and the results were correlated with those of histopathologic examination in 14 cases. In this study, the concordance between FNAC plus FCM and histopathologic examination was 90% for low-grade non-Hodgkin's malignant lymphomas (NHLs) and 83% for high-grade NHL. The limits of this morphologic and phenotypic approach are (i) partial tumor infiltrations, (ii) Hodgkin lymphoma, and (iii) T-cell NHL. In conclusion, it may be said that this combined approach is very useful for diagnosis and follow-up of patients but requires teams experienced in the sampling technique and the morphologic diagnosis of the various types of low-grade NHL in which supplementary ancillary studies may be performed when morphology and flow cytometry immunophenoyping are not conclusive.

Adolescent↗
PubMed2005

S-phase fraction as an independent prognostic factor of long-term overall survival in patients with early-stage or locally advanced invasive breast carcinoma.

BACKGROUND: Large retrospective archival studies of S-phase fraction (SPF) measured by DNA flow cytometry in patients with breast carcinoma have shown its long-term prognostic relevance. However, contradictory results have also been reported, some of them being related to the various methods of SPF calculation using different commercially available software. METHODS: DNA flow cytometric list mode data, initially computed with Cellfit software, were blindly reanalyzed using Modfit and Multicycle software. The data, acquired prospectively between 1990 and 2003 from cytologic fine-needle aspiration biopsy samples of 397 patients with breast carcinoma, were compared with patient outcome with a median follow-up of 99 months (8.2 yrs). RESULTS: Measurement of SPF was successful in 321 (81.7%), 362 (92.1%), and 335 cases (85.2%) by means of the Cellfit, Modfit, and Multicycle software programs, respectively. In 306 cases (77.9%), SPF values were obtained using all 3 methods. Comparisons between SPF measurements showed a good agreement between Modfit and Multicycle computations. In the series of 306 patients, SPF median values of 2.5%, 4.3%, and 5.45% for Cellfit, Modfit, and Multicycle, respectively, were also found to be statistically different. Regardless of the software used, high SPF defined as above the median value was an independent factor of prognosis in a multivariate analysis including all traditional clinicopathologic parameters. It is noteworthy that this was also observed in the subgroups of patients either treated by primary surgery for an early tumor (n = 133) or by neoadjuvant chemotherapy for a locally advanced breast carcinoma (n = 173). CONCLUSIONS: The data in the current study supported the prognostic relevance of SPF measurement in predicting the long-term overall survival of patients with early-stage or locally advanced invasive breast carcinoma.

Adult↗
PubMed2005

Cost-effectiveness of liquid-based cytology with or without hybrid-capture II HPV test compared with conventional Pap smears: a study by the French Society of Clinical Cytology.

Many articles concerning conventional Pap smears, ThinPrep liquid-based cytology (LBC) and Hybrid-Capture II HPV test (HC II) have been published. This study, carried out by the French Society of Clinical Cytology, may be conspicuous for several reasons: it was financially independent; it compared the efficiency of the conventional Pap smear and LBC, of the conventional Pap smear and HC II, and included an economic study based on real costs; for all the women, a "gold standard" reference method, colposcopy, was available and biopsies were performed whenever a lesion was detected; The conventional Pap smear, the LBC (split-sample technique), the colposcopy, and the biopsies were done at the same time. This study included 2,585 women shared into two groups: a group A of a high-risk population, a group B of a screening population. The statistical analysis of the results showed that conventional Pap smears consistently had superior or equivalent sensitivity and specificity than LBC for the lesions at threshold CIN-I (Cervical Intraepithelial Neoplasia) or CIN-II or higher. It underlined the low specificity of the HC II. Finally, the LBC mean cost was never covered by the Social Security tariff.

Adult↗
PubMed2004

Gene expression profiling of differentiated thyroid neoplasms: diagnostic and clinical implications.

PURPOSE: The purpose of this research was to identify novel genes that can be targeted as diagnostic and clinical markers of differentiated thyroid tumors. EXPERIMENTAL DESIGN: Gene expression analysis using microarray platform was performed on 6 pathologically normal thyroid samples and 12 primary follicular and papillary thyroid neoplasms. Microarrays containing probes for 5,760 human full-length cDNAs were used for hybridization with total RNA from normal and tumor thyroid samples labeled with Cy3-dUTP and Cy5-dUTP, respectively. Scanned array images were recorded, and data analysis was performed. Selected sets of differentially expressed genes were analyzed using quantitative real-time reverse transcription-PCR for verification. RESULTS: We identified 155 genes that differentiate histologically normal thyroid tissues from benign and malignant thyroid neoplasms. Of these 75 genes were differentiated between follicular neoplasms (adenoma and carcinoma) and the follicular variant of papillary carcinoma. Purely follicular neoplasms (adenomas and carcinomas) shared many genetic profiles, and only 43 genes were distinctly different between these tumors. Hierarchical cluster analysis also differentiated conventional papillary carcinoma from its follicular variant and follicular tumors. The differentially expressed genes were composed of members of cell differentiation, adhesion, immune response, and proliferation associated pathways. Quantitative real-time reverse transcription-PCR analysis of selected genes corroborated the microarray expression results. CONCLUSIONS: Our study show the following: (1) differences in gene expression between tumor and nontumor bearing normal thyroid tissue can be identified, (2) a set of genes differentiate follicular neoplasm from follicular variant of papillary carcinoma, (3) follicular adenoma and carcinoma share many of the differentiated genes, and (4) gene expression differences identify conventional papillary carcinoma from the follicular variant.

Adenocarcinoma, Follicular↗
PubMed2004

Comparative genomic hybridization analysis of hereditary swine cutaneous melanoma revealed loss of the swine 13q36-49 chromosomal region in the nodular melanoma subtype.

Genetic alterations implicated in malignant melanoma are still poorly understood. Malignant melanomas present highly variable histologic and cytologic patterns. The aim of the present study is to define genomic imbalances associated with the development of 2 histologic types of swine hereditary cutaneous melanoma. We have investigated 11 swine tumors by comparative genomic hybridization (CGH), 4 superficial spreading melanomas (SSMs) and 7 nodular melanomas (NMs). Following laser capture microdissection and degenerate oligonucleotide primed-polymerase chain reaction, we were able to isolate and then amplify DNA from the 2 histologic subtypes. Consensus regions of chromosome gains were identified on both histologic subtypes, on swine chromosomes 3p13-p17 (75% of the SSMs and 71% of the NMs), 12q (100% of the SSMs and 57% of the NMs) and 14q11-q21 (75% of the SSMs and 42% of NMs). Chromosomal loss was restricted to NM lesions and the swine 13q36-49 region was lost in 100% of the NMs. Interphase fluorescence in situ hybridization with a probe mapping to the 13q41-q42 region indicates loss of the corresponding region on NM lesions. Taking into account this CGH analysis and the comparative genomic data between swine and human genomes, we suggest that a role for the human chromosomes 3p11-qter and chromosome 21 losses should be investigated in human nodular melanoma progression.

Animals↗
PubMed2004

Chromatin assembly factor-1, a marker of clinical value to distinguish quiescent from proliferating cells.

Histone synthesis and chromatin assembly are mainly associated with DNA replication and are thus intimately involved in cell cycle regulation. The expression of key components involved in these events in human cells was studied in relation to cell-proliferative status. Among several chromatin assembly factors, chromatin assembly factor (CAF)-1 stood out as the most discriminating marker of the proliferative state. We show, using both immunofluorescence and Western blot analysis, that the expression of both CAF-1 large subunits, p150 and p60, is massively down-regulated during quiescence in several cell lines. Upon exit from the quiescent state, the CAF-1 subunits are re-expressed early, before DNA replication. The amounts of either total or chromatin-associated pools of CAF-1 proteins correlate directly with cell proliferation. Regulation of CAF-1 expression is partly controlled at the RNA level, as shown by quantitative reverse transcription-PCR and Northern blot experiments. Biological material from benign and malignant human breast tumors analyzed by immunocytochemistry and immunohistochemistry exhibits a strong positive correlation between CAF-1 p60 expression and the following proliferation markers: S-phase fraction (r = 0.84, P < 0.0001); Ki-67 (r = 0.94, P < 0.0001); and proliferating cell nuclear antigen (r = 0.95, P = 0.0001). We discuss the advantages of using CAF-1 to assess cell proliferation. High CAF-1 p60 levels are also shown to be associated with various prognostic factors. Our data highlight the precise association of CAF-1 expression with the proliferative state and validate the use of this factor as a useful proliferation marker and prognostic indicator in malignant and benign breast lesions.

Biomarkers, Tumor↗
PubMed2004

Stromal infiltration as a predictor of tumor invasion in breast fine-needle aspiration biopsy.

Clinical management of in situ carcinoma of the breast is different from invasive carcinomas. Thus, it is important to find cytomorphologic criteria to distinguish between these two entities. The current study is designed to assess whether, by applying strict cytologic criteria, the status of stromal invasion can be predicted. In this retrospective study, 223 consecutive nonpalpable tumors sampled by ultrasound-guided breast fine-needle aspirates with diagnosis of in situ and invasive carcinoma with histologic follow-up evaluation were retrieved. Ten cytologic parameters were evaluated, which included cellular clustering, eosinophilic differentiation, necrosis, tubular structures, dirty background, nuclear anisonucleosis, cellular pleomorphism, cribriform pattern, tubular structures, and stromal infiltration. Among all the parameters examined, stromal infiltration was the most powerful predictor of status of invasion. Stromal infiltration was significantly higher in invasive (88%) than in situ (11%), P < 0.0001. In contrast, cribriform pattern (16% vs 36%) and necrosis (19% vs 59%) were more frequently seen in situ than in invasive carcinomas with P-values of 0.0008 and <0.0001, respectively. This study demonstrates that stromal infiltration defined by strict criteria may predict the status of tumor invasion in breast fine-needle aspirates. The combination of stromal infiltration and cribriform pattern and necrosis in aspirates may provide an opportunity in introducing a "predictive index" to differentiate between an in situ versus an invasive process.

Adenocarcinoma↗
PubMed2004

Fine-needle sampling in malignant phyllodes tumors: clinicopathologic study of 22 cases seen at the Institut Curie.

The preoperative cytological diagnosis of malignant phyllodes tumor (MPT) is challenging due to the heterogeneity of its clinical, radiological, and morphological presentation. To better define the cytopathological characteristics of MPT, we reviewed 22 examples seen at the Institut Curie. The original cytologic diagnosis was benign breast tumor in four cases (18.2%), suspicious in seven cases (31.8%) (low-grade phyllodes tumor in six cases needing histological evaluation, suspicious of sarcoma in one case), and malignant in 11 cases (50%). Smears were composed of different proportions of clusters of epithelial cells (68.2%), phyllodes fragments (31.8%), spindle cells within stromal tissue (31.8%), isolated spindle-shaped or round cells (45.5%), and bipolar naked nuclei (22.7%). Giant cells and mitotic figures were also occasionally seen. The cytological findings on smears were correlated with histopathological observations. One of the difficulties to reach an accurate cytological diagnosis for MPT is the frequent overwhelming of clearly malignant sarcomatous cell by the presence of largely predominant clusters of epithelial cell.

Adult↗
PubMed2004

Peroxisome proliferator-activated receptor-gamma ligands as cell-cycle modulators.

The peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors, initially described as molecular targets for compounds which induce peroxisomal proliferation. PPAR-gamma, the best characterized of the PPARs, is a ligand-activated transcription factor and a key regulator of adipogenic differentiation and glucose homeostasis. PPAR-gamma ligands have recently been demonstrated to affect proliferation, differentiation and apoptosis of different cell types. Recent in vitro and in vivo studies suggest the importance of specific PPAR-gamma ligands as cell-cycle modulators, establishing their antineoplastic properties. In this review, the latest knowledge on the role of PPAR-gamma ligands as cell-cycle modulators is presented, discussing also their role in cell proliferation, apoptosis and cancer.

Animals↗
PubMed2004

[Contribution of multiple correspondence analysis in histopathology].

Descriptive statistics in the field of medicine are usually based on univariate analysis. However, a multivariate descriptive analysis can often be usefull to jointly describe all variables considered for study. This multivariate description is difficult to perform and visualize for more than three variables at a time. Multiple correspondence analysis (MCA) provides a means of performing multivariate description of categorical data. The method consists in projecting the data of an n-dimensional space which is constituted by the variables under study onto a succession of two-dimensional planes. The relationships between variables can then be deduced from the relative positions of the modalities of the variables on the planes. At the same time, numerical indices are used in parallel to specify and validate the observed relationships. The use of MCA is illustrated with a prospective series of renal carcinomas for which different histological characteristics are given. The main applications of MCA are detailed with comments on practical implementation.

Carcinoma, Renal Cell↗
PubMed2004

[Cytopathology of malignant blastematous tumors].

Since almost all childhood blastematous tumors belong to the group of non hematological small round cell tumors we describe here the cytopathological aspects of the most frequent of these neoplasms i.e. neuroblastoma, nephroblastoma, rhabdomyosarcoma, peripheral neuroectodermic tumors, and emphasize the role of molecular techniques applicable to cytological material obtained from fine-needle aspiration to help the pediatrician in tailoring therapy.

Child↗
PubMed2004

Potential rapid assessment of breast cancer prognosis using induced chromosome condensation performed on cytological specimens.

We have previously shown that assessment of chromosome alteration rate by cytogenetics is well correlated with breast cancer prognosis factors. As karyotypes are usually difficult to obtain from solid tumors using conventional methods, a new approach is proposed. Metaphase-like chromosomes were directly obtained following chromosome condensation using calyculin A (okadaic acid) from cytologic specimens of breast cancers sampled by fine needle. Chromosome counts and rearrangement rates were established in a series of 45 tumors, as early as 24-48 h after sampling. A high rate of rearranged chromosomes was found to correlate with high histological grade, TNM stage and S-phase fraction, loss of estrogen receptor expression and DNA aneuploidy. The indication of genome alteration provided by this method constitutes a simple, potent and early potential prognostic factor in breast cancer directly applied on cytological specimens.

Adult↗
PubMed2004

Clinical and histopathological characterization of cutaneous melanomas in the melanoblastoma-bearing Libechov minipig model.

Spontaneous animal tumors appear to be highly suitable models to study human oncology and cancer therapy. The aim of this study was to characterize the clinical and histological features of hereditary melanocytic lesions found in the French herd of melanoblastoma-bearing Libechov minipigs (MeLiM) and their Duroc crossbreeds. Clinically, we discriminated between three types of melanocytic skin lesions, which offer a lesion continuum from lentigo to metastatic melanomas. More than 70% of these lesions appear on piglets before they are 3 months old and preferentially on homogeneous black coat piglets. The incidence of melanoma reaches 50% in MeLiM. Most of the highly invasive melanomas regressed spontaneously in the first year of the piglet's life and the regression was followed by hair, skin and iris depigmentation. A histopathological study was conducted according to the human melanoma classification. Except for lentigo maligna, we observed the three main types of human melanoma in swine [superficial spreading melanoma (SSM), nodular or unclassified melanoma] with an excess of SSM (59-67%). The histological events leading to total spontaneous regression are chronologically described. The genetic predisposition, the high incidence of melanoma, the clinical and histopathological features similar to the human disease and the high rate of spontaneous regression offer an opportunity to use this model for studying genetic events controlling melanoma development and regression and the biological mechanisms involved in oncogenesis and anti-cancerous self-defense.

Animals↗
PubMed2004

Solid tumor DNA content analysis.

Flow cytometric DNA content analysis provides a rapid and reliable analysis of DNA ploidy and the proliferative fraction of tumor specimens. Both archival and fresh specimens are suitable for this technique. This information can be used in conjunction with traditional prognostic factors in the biological assessment of certain carcinomas. Among these tumors are early stages of breast, colon, lung, and bladder carcinomas.

Carcinoma↗
PubMed2003

ThinPrep-processed fine-needle samples of breast are effective material for RNA- and DNA-based molecular diagnosis: application to p53 mutation analysis.

BACKGROUND: Fine-needle sampling is the least invasive method of in vivo breast carcinoma sampling and can provide material for breast carcinoma diagnosis. The aim of the current study was to assess the accuracy of molecular diagnosis techniques using fine-needle sample (FNS) material stored in PreservCyt (Cytyc Corp., Boxborough, MA). METHODS: The p53 tumor suppressor gene was chosen as a model because it can be used for DNA, RNA, and protein analysis. Molecular analysis was performed using a yeast functional assay and DNA sequencing. p53 accumulation was evaluated by immunocytochemistry. RESULTS: DNA and protein analysis indicated that samples stored for periods of several months, either at room temperature, 4 degrees C, or -20 degrees C, can be processed reliably. For RNA-based diagnosis, samples were still intact after 5 months of storage in PreservCyt at 4 degrees C. In addition, using FNS material that was stored for 16 months at 4 degrees C, the authors detected p53 mutations with either the functional assay for separating alleles in yeast (an RNA-based functional assay) or direct cDNA sequencing. CONCLUSIONS: Fine-needle samples stored in PreservCyt at 4 degrees C are very good material for molecular diagnosis techniques. In addition, it is feasible to adopt a strategy of storing excess FNS material to create cellular banks that will be invaluable for future gene studies.

Biopsy, Needle↗
PubMed2003

Cross sectional study of conventional cervical smear, monolayer cytology, and human papillomavirus DNA testing for cervical cancer screening.

OBJECTIVES: To compare the sensitivity, specificity, and interobserver reliability of conventional cervical smear tests, monolayer cytology, and human papillomavirus testing for screening for cervical cancer. DESIGN: Cross sectional study in which the three techniques were performed simultaneously with a reference standard (colposcopy and histology). SETTING: Public university and private practices in France, with complete independence from the suppliers. PARTICIPANTS: 828 women referred for colposcopy because of previously detected cytological abnormalities and 1757 women attending for routine smears. MAIN OUTCOME MEASURES: Clinical readings and optimised interpretation (two blind readings followed, if necessary, by consensus). Sensitivity, specificity, and weighted kappa computed for various thresholds of abnormalities. RESULTS: Conventional cervical smear tests were more often satisfactory (91% v 87%) according to the Bethesda system, more reliable (weighted kappa 0.70 v 0.57), and had consistently better sensitivity and specificity than monolayer cytology. These findings applied to clinical readings and optimised interpretations, low and high grade lesions, and populations with low and high incidence of abnormalities. Human papillomavirus testing associated with monolayer cytology, whether systematic or for atypical cells of undetermined significance, performed no better than conventional smear tests. CONCLUSIONS: Monolayer cytology is less reliable and more likely to give false positive and false negative results than conventional cervical smear tests for screening for cervical cancer.

Colposcopy↗