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P Birembaut

Publications and source records attributed to P Birembaut.

At least 19 recordsLinked to original sources
PubMed2007

[Multiple recurrent papillomas of the breast: case report].

We report the case of a patient presenting multiple recurrent papillomas of the breast. This mild mammary pathology, developed at the expense of the galactophoric ducts, recurred four times, in a nodular way, in spite of in sano surgical resection. The retrospective study of the cell proliferation and the DNA quantification of the cells constitutive of the papillomas, on several samples, underlined evolutive lesions, which could be predictive of a malignant degeneration. This observation allows us to discuss the management of this rare mild mammary pathology, which can sometimes lead to invasive breast carcinoma.

Adult↗
PubMed2007

Human airway surface epithelial regeneration is delayed and abnormal in cystic fibrosis.

Cystic fibrosis (CF) at an advanced stage of the disease is characterized by airway epithelial injury and remodelling. Whether CF remodelling is related to infection and inflammation or due to an abnormal regenerative process is still undecided. We have recently established the expression and secretion profiles of interleukin (IL)-8, matrix metalloproteinase (MMP)-7, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 during non-CF airway epithelial regeneration in a humanized nude mouse xenograft model. To enhance our understanding of CF remodelling, we compared the regeneration process of non-infected human CF and non-CF nasal epithelia. In both CF and non-CF situations, epithelial regeneration was characterized by successive steps of cell adhesion and migration, proliferation, pseudostratification, and terminal differentiation. However, histological examination of the grafts showed a delay in differentiation of the CF airway epithelium. Cell proliferation was higher in the regenerating CF epithelium, and the differentiated CF epithelium exhibited a pronounced height increase and basal cell hyperplasia in comparison with non-CF epithelium. In addition, while the number of goblet cells expressing MUC5AC was similar in CF and non-CF regenerated epithelia, the number of MUC5B-immunopositive goblet cells was lower in CF grafts. The expression of human IL-8, MMP-7, MMP-9, and TIMP-1 was enhanced in CF epithelium, especially early in the regenerative process. Together, our data strongly suggest that the regeneration of human CF airway surface epithelium is characterized by remodelling, delayed differentiation, and altered pro-inflammatory and MMP responses.

Adolescent↗
PubMed2006

Expression of a disintegrin and metalloprotease (ADAM and ADAMTS) enzymes in human non-small-cell lung carcinomas (NSCLC).

A Disintegrin and Metalloprotease (ADAM) are transmembrane proteases displaying multiple functions. ADAM with ThromboSpondin-like motifs (ADAMTS) are secreted proteases characterised by thrombospondin (TS) motifs in their C-terminal domain. The aim of this work was to evaluate the expression pattern of ADAMs and ADAMTS in non small cell lung carcinomas (NSCLC) and to investigate the possible correlation between their expression and cancer progression. Reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot and immunohistochemical analyses were performed on NSCLC samples and corresponding nondiseased tissue fragments. Among the ADAMs evaluated (ADAM-8, -9, -10, -12, -15, -17, ADAMTS-1, TS-2 and TS-12), a modulation of ADAM-12 and ADAMTS-1 mRNA expression was observed. Amounts of ADAM-12 mRNA transcripts were increased in tumour tissues as compared to the corresponding controls. In sharp contrast, ADAMTS-1 mRNA levels were significantly lower in tumour tissues when compared to corresponding nondiseased lung. These results were corroborated at the protein level by Western blot and immunohistochemistry. A positive correlation was observed between the mRNA levels of ADAM-12 and those of two vascular endothelial growth factor (VEGF)-A isoforms (VEGF-A(165) and VEGF-A(121)). Taken together, these results providing evidence for an overexpression of ADAM-12 and a lower expression of ADAMTS-1 in non-small-cell lung cancer suggest that these proteases play different functions in cancer progression.

ADAM Proteins↗
PubMed2006

Metalloproteinase-2, -7 and -9 and tissue inhibitor of metalloproteinase-1 and -2 expression in normal, hyperplastic and neoplastic endometrium: a clinical-pathological correlation study.

BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors are key-players in extracellular matrix and basement membrane degradation, and are involved in both physiological and malignant processes. The aim of this study was to examine MMP-2, -7 and -9 and TIMP-1 and -2 expression in normal, hyperplastic and malignant endometrium, and their relation to clinical and histological prognostic factors. MATERIALS AND METHODS: We performed qualitative and semi-quantitative immunohistochemical analysis of 20 samples of normal endometrium (10 in the proliferative phase, 10 in the secretory phase), 39 samples of hyperplastic endometrium (17 without atypia and 22 with atypia) and 38 samples of endometrioid carcinoma, by using specific monoclonal antibodies. RESULTS: In normal endometrium, epithelial expression of MMP-2 (P = 0.0007), MMP-7 (P = 0.0002) and TIMP-2 (P = 0.0004) was increased during the proliferative phase of the menstrual cycle. MMP-2 expression correlated negatively with TIMP-2 expression (P = 0.001, rho = 0.702). Endometrial stromal cells in the secretory phase showed strong MMP-2 expression (P = 0.004) and weak MMP-7 (P = 0.001) and TIMP-1 expression (P = 0.01). In hyperplastic endometrium, the presence of atypia was associated with lower TIMP-2 expression (P = 0.005) and was also associated with a trend towards higher MMP-2 expression. Endometrial stromal cell expression of MMP-2, -7 and -9 and TIMP-1 and -2 did not differ between hyperplastic endometrium with and without atypia. A gradient of MMP-2 and -9 expression was observed from hyperplastic endometrium to endometrial carcinomas. In endometrial carcinomas, MMP-2 expression increased (P = 0.0004) and TIMP-2 expression decreased (P = 0.0005) with the histological grade. TIMP-2 expression correlated with myometrial invasion (P = 0.005), lymphovascular space involvement (P = 0.008) and lymph node involvement (P = 0.007). CONCLUSION: These results support the involvement of MMPs and TIMPs in endometrial carcinogenesis. Strong MMP-2 and weak TIMP-2 expression were the most potent markers of endometrial malignancies with a high risk of local and distant spread.

Endometrial Neoplasms↗
PubMed2005

Less HLA-G expression in Plasmodium falciparum-infected third trimester placentas is associated with more natural killer cells.

During pregnancy, maternal immune tolerance of the fetal semi-allogeneic graft is partly the consequence of extravillous trophoblast HLA-G expression and its interaction with natural killer (NK) cells. Plasmodium falciparum malaria is frequently associated with maternal and fetal complications. Local HLA-G expression and the number of NK cells were evaluated immunohistochemically in P. falciparum-infected and uninfected placentas (15 each) collected in a seasonal malaria-hypoendemic area. In control placentas, HLA-G was almost always expressed in extravillous trophoblast whereas, in infected placentas, it was significantly more weakly expressed in extravillous trophoblast but was also detected in intervillous space macrophages. NK cells were evaluated in intervillous and intravillous spaces and in basal plate. NK cells were always more abundant in basal plate than in intervillous and intravillous spaces in infected or control placentas. For each area, more NK cells were seen in infected than control placentas. These data suggest that HLA-G down-regulation and more NK cells in placentas may be among the mechanisms involved in poor birth outcome associated with P. falciparum infection.

Adolescent↗
PubMed2005

[Gestational trophoblastic diseases: a retrospective study from 1997 to 2003].

BACKGROUND: Trophoblastic diseases correspond to a very heterogeneous group of rare pathology in young women which fertility should be preserved. PATIENT AND METHODS: We conducted a retrospective study from 1997 to 2003, including all patients with molar pregnancy or trophoblatic tumor in our department of Obstetrics and Gynecology. RESULTS: Fifteen patients were identified with 9 molar pregnancies, 5 trophoblastic tumors and 1 placental tumor of implantation site. The outcome was favorable for 14, and one patient died from her metastatic disease. For 4 patients we asked our university colleague for the optimal approach. DISCUSSION: Management of molar pregnancies is well established. Persistent gestational disease is more rare and problematic with potential metastatic dissemination. Multidisciplinary care is often needed. CONCLUSION: Persistent gestational disease should be managed in a highly specialized centre, as developed in the Lyon University Hospital.

Adolescent↗
PubMed2005

Comparison of liquid based cytology and histology for the evaluation of HER-2 status using immunostaining and CISH in breast carcinoma.

BACKGROUND: HER-2 amplification is an important prognostic biomarker and treatment determinant in breast carcinoma. AIMS: To correlate immunocytochemical (ICC) expression of HER-2 and gene amplification determined by chromogenic in situ hybridisation (CISH) using liquid based cytology (LBC) with immunohistochemistry (IHC) and CISH using histological samples of the same breast carcinomas. METHODS: Frozen sections and cytobrushings of 103 breast carcinomas were analysed. Four techniques were performed on each tumour: two on LBC samples (ICC, and CISH, both graded as positive, indeterminate, or negative) and two on histological samples (IHC and CISH). Two cell lines (MCF-7, negative; BT 474, positive) were used as controls for cytological analysis. A complementary fluorescence in situ hybridisation technique was carried out in histological samples with low amplification (4-10 dots/nucleus). RESULTS: Interobserver agreement for the four techniques calculated by the kappa coefficient indicated a substantial agreement. Nine cases failed in cytology because of poor cellularity. Among 94 cases, 19 were amplified; 73, 12, and 9 tumours were scored 0 or 1+, 2+, and 3+, respectively by IHC and 75, 13, and 6, respectively, by ICC. CISH found no amplification in 72 tumours. Correlations between the IHC and CISH results in the histological and cytological samples were always significant. CONCLUSIONS: Her-2 status could be determined in LBC samples and correlated well with reference histological methods using in situ hybridisation. ICC was less reliable because of the presence of the cytoplasmic membrane. However, these results should be confirmed by a large multicentre study.

Adult↗
PubMed2005

Usefulness of HPV testing in the follow-up of untreated cervical low grade lesions.

The aim of the present work was to evaluate the usefulness of high-risk human papillomavirus (HR-HPV) testing for the follow-up of women with untreated low grade cervical squamous cell lesions (LSIL). For that, 412 women with a cytological diagnosis of LSIL at entry were monitored by cytology, HR-HPV testing with the Hybrid Capture II assay (HC-II) and colposcopy. Our primary endpoint was clinical progression defined by the presence of a high grade cervical intraepithelial neoplasia (CIN2 and CIN3) at the biopsy. At baseline, histological control revealed 10 CIN2 and 11 CIN3 only in the cohort of women HR-HPV+. In the follow-up, 4 CIN2 and 8 CIN3 were detected, always in the women initially HR-HPV+. Thus, the recurrence of a HR-HPV+ infection clearly selects a population at high-risk for CIN2-3. The semi-quantitative appreciation of the viral load with HC-II could not be used as a good prognostic factor for the follow-up of women with LSIL. HR-HPV testing reduces the number of cytology and colposcopy examinations in the follow-up of women aged >35 years when HPV testing is initially negative. Thus HR-HPV testing should be reserved for the follow-up of this population of women initially HR-HPV+ and proposed 6 to 12 months after the cytological diagnosis of LSIL.

Adolescent↗
PubMed2004

Negative human papillomavirus testing in normal smears selects a population at low risk for developing high-grade cervical lesions.

High-risk human papillomaviruses (HR-HPV) are the necessary cause of cervical carcinomas and there is an increasing interest in using HR-HPV DNA detection in adjunction to cytological examination for primary cervical screening. To determine whether women with a normal smear negative for HR-HPV DNA detection with the Hybrid Capture II assay might represent a low-risk population for developing a high-grade squamous intraepithelial lesion (HSIL), 4401 women have been followed in a period of 12-72 months (median=34 months). During this follow-up, four HSIL and one microinvasive carcinoma have been detected in this cohort (three in the cohort of 3526 women >29 years). The global negative predictive value (NPV) of double-negative tests is thus of 99.9% (ninety-five percent confidence interval (95% CI): 99.8-100%), whereas cytology alone gives an NPV of 99.2% (95% CI: 98.9-99.5%). If we obtain a second negative HR-HPV test 1-2 years after the initial test, the NPV is 100%. The NPV is also of 100% in the cohort of women >49 years. We conclude that all these women could be safely screened at longer intervals between 3 and 5 years. This policy will offset the increased costs induced by an additional HR-HPV testing in primary screening.

Adolescent↗
PubMed2004

DNA image cytometry on biopsies can help the detection of localized Gleason 3+3 prostate cancers.

PURPOSE: In spite of classifications based on digital rectal examination, prostate specific antigen (PSA), transrectal echography and histological analysis, 20% to 40% of operated prostate adenocarcinomas are not yet organ confined. New diagnostic features to predict extracapsular invasion before treatment are needed to avoid surgical extraction within positive margins. MATERIALS AND METHODS: A retrospective study was performed for 74 prostate adenocarcinomas with Gleason 3+3. A total of 54 organ confined tumors (T1T2) at digital rectal examination were compared with 20 nonorgan confined tumors (T3T4). Image cytometric DNA analysis was performed on prostate initial biopsies. DNA ploidy results were compared in both groups for values of PSA greater than 15, less than 15 and less than 10 ng/ml. RESULTS: For a PSA rate less than 15 ng/ml, 83.8% of T1T2 were diploid vs 33% T3T4 (p = 0.042). For a PSA rate less than 10 ng/ml, 96% of T1T2 were diploid vs 33% T3T4 (p = 0.025). CONCLUSIONS: DNA ploidy appears to be an interesting feature at diagnosis. When in doubt about the localized character of a tumor, DNA ploidy it makes it possible to predict a nonorgan confined tumor. Gleason 3+3 prostate cancers that are organ confined at digital rectal examination are more often diploid than T3T4 tumors. The prognostic interest in DNA ploidy is more reserved because of its correlation with PSA level.

Adenocarcinoma↗
PubMed2001

Quantitative cell dispersion analysis: new test to measure tumor cell aggressiveness.

Tumor progression requires the dispersion of epithelial cells from neoplastic clusters and cell invasion of adjacent stromal connective tissue. Aiming at demonstrating the precise relationships between cell dispersion and cell invasion, related respectively to expression of E-cadherin/catenin complex and matrix metalloproteinases (MMPs), we developed an original in vitro model of cell dispersion analysis. Our study reports the validation of this model that allowed us to analyze and quantify the cell cohesion level by means of time-lapse videomicroscopy and computer analysis based on the observation of spatial and temporal cell distribution. Our model was able to distinguish 2 groups among different human bronchial and mammary epithelial cells previously characterized for the expression of E-cadherin/catenin complex and MMPs and their invasive capacity in the Boyden chamber assay. The first group (16HBE14o(-), MCF-7, T47D) that expressed membranous E-cadherin and beta-catenin, and was negative for MMP-2 expression and non-invasive, displayed a highly cohesive pattern corresponding to a cluster spatial distribution. The second group (Beas2B, BZR, BZR-T33, MDA-MB-231, MDA-MB-435, BT549 and HS578T) that was invasive and showed lack of expression of E-cadherin and a cytoplasmic redistribution of beta-catenin, displayed a dispersed pattern corresponding to a random spatial distribution. Downregulation of E-cadherin by a blocking antibody induced a more random distribution. Conversely, expression of E-cadherin by cDNA transfection induced a cluster distribution. Moreover, tumor cell lines that co-expressed MT1-MMP and MMP-2 (Beas2B, BZR, BZR-T33, MDA-MB-435, BT549 and HS578T) showed a more dispersed pattern than tumor cell lines that did not express MMP-2 (MDA-MB-231). In conclusion, we demonstrated that the spatial group behavior of cell lines, i.e., their cohesion/dispersion ability, reflects their invasive properties. Thus, this model of cell dispersion analysis may represent a new test to measure tumor cell aggressiveness.

Breast↗
PubMed2001

Human papillomavirus testing in primary screening for the detection of high-grade cervical lesions: a study of 7932 women.

High-risk human papillomaviruses (HR-HPV) are the necessary cause of cervical carcinomas. To determine whether HPR-HPV DNA detection in primary routine screening could represent a sensitive and reliable technique for the detection of high-grade squamous intraepithelial lesions (HGSIL), laboratory analysis using 2 cytologic techniques (conventional and liquid-based), HPV testing with Hybrid Capture II assay (HC-II), followed by colposcopic examination of women with abnormal cervical finding and/or persistent HR-HPV infection, was conducted in 7932 women who had routine cervical examination. The sensitivity of HPV testing for detecting a histologically proven HGSIL was 100%, higher than that of conventional (68.1%) and liquid-based (87.8%) cytology. The low specificities of 85.6% and 87.3% of HPV testing slightly increased to 88.4% and 90.1% if HPV testing was reserved for woman >30 years old. The quantitative approach provided by the HC-II assay for the assessment of the viral load was not reliable for predicting HGSIL in normal smears. HR-HPV testing could be proposed in primary screening in association with cytology. With conventional cytology it significantly improves the detection of HGSIL. With the use of the same cervical scrape for HPV testing and liquid-based cytology, HR-HPV testing would allow to select positive samples treated in a second time for cytology which gives a good specificity.

Adolescent↗
PubMed2001

uPA/plasmin system-mediated MMP-9 activation is implicated in bronchial epithelial cell migration.

To examine the effects of the uPA/plasmin system on cell migration in relation to the activation of MMP-9, we used ex vivo and in vitro wound-repair models of human bronchial epithelial cells and videomicroscopy techniques that make possible cell tracking and quantification of cell migration speeds. We observed that uPA was only detected in migrating cells at the wound edges and located at crucial sites for cell/extracellular matrix interactions. The implication of uPA in human bronchial epithelial cell migration was studied by incubating cultures with a monoclonal antibody raised against uPA and these experiments led to a 70% reduction in cell velocity. To examine the effects of the plasmin system on cell migration, we incubated cultures with increasing concentrations of plasmin or activated MMP-9. We observed a significant dose-dependent increase in cell migration velocity with plasmin (P < 0.001) and MMP-9 (P < 0.001). Moreover, addition of exogenous plasmin led to a twofold increase of activated MMP-9 in migrating cells. We also demonstrated that the addition of anti-uPA IgG led to an inhibition of 43% of activated MMP-9. In conclusion, these results show that uPA is involved in human bronchial epithelial cells migration. This action is mediated by the generation of plasmin, which in turn activates MMP-9, thus making possible cell migration.

Antibodies, Monoclonal↗
PubMed2001

Human papillomavirus infection and anogenital condyloma in bone marrow transplant recipients.

BACKGROUND: Secondary malignant diseases are late complications after allogeneic bone marrow transplantation (BMT). Anogenital lesions associated with human papillomavirus (HPV) infection have been described in renal transplant recipients but not after BMT. HPV types 16 and 18 are strongly linked to the malignant transformation. METHODS: In a series of 238 patients with allogeneic BMT, three had anogenital lesions. We looked for HPV in DNA extracted from embedded tissue to study HPV genotypes, p53 expression, and ploidy. RESULTS: In two patients, HPV sequences were detected. One of them, with giant condyloma, had HPV type 18 and two aneuploid clones, but p53 expression was not found. CONCLUSION: As in solid organ transplant recipients, anogenital condyloma may develop after BMT. Because the oncoprotein of HPV is able to bind and to degrade p53, it may lead to genetic instability, and subsequently to malignant transformation.

Adult↗
PubMed2001

DNA image cytometry and human papillomavirus (HPV) detection help to select smears at high risk of high-grade cervical lesions.

Three samples were submitted from women undergoing routine screening (n=910): two smears (one for routine cytology and one for DNA image cytometry) and a scrape for human papillomavirus (HPV) testing. DNA histograms were classified as suspect in cases of aneuploidy, polyploidy, and/or diploidy with a high proliferation rate. Follow-up was available in 239 cases. The primary end-point was the presence of a high-grade squamous intraepithelial lesion (HGSIL) at biopsy. Seventy women (7.7%) had a high-risk (HR) HPV infection and a suspect DNA profile. In 77 women with cytological abnormalities, 28 HGSILs were detected: four with a prior diagnosis of ASCUS (all HR-HPV infected including three with a suspect DNA profile), three with smears evocative of LGSIL (all with HR-HPV infection and a suspect DNA profile), and 21 with smears evocative of HGSIL (all with HR-HPV infection and 20 with a suspect DNA profile). During the follow-up period, out of 239 women with a cytologically normal smear at first entry, five developed a HGSIL; all were HR-HPV-positive and four had a suspect DNA profile at the first smear. HR-HPV detection alone gives a sensitivity of 100% for the detection of HGSIL, with a specificity of 84.3%, whereas DNA measurement associated with HPV testing significantly enhances the specificity to 95.4%. Thus, the combination of HPV testing and DNA measurement provides a highly sensitive and specific evaluation of the risk of HGSIL on cervical smears.

Cervix Uteri↗
PubMed2001

Expression of matrix metalloproteinases in healthy and diseased human gingiva.

BACKGROUND, AIMS: The aim of our study was to investigate the patterns of several metalloproteinases (MMP-1, MMP-2 and MT1-MMP) mRNAs expression using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and to correlate them with clinical parameters and bacteriological diagnosis in healthy versus diseased human gingiva. METHODS: To identify the cell origin of MMP production, in situ hybridization (ISH) was also performed for the MMPs on the same samples. 17 gingival biopsies were collected (13 affected by advanced periodontitis and 4 healthy used as controls) and plaque index, gingival index, pocket depth and bleeding on probing were measured. Subgingival microbial samples were also collected to be analysed by a DNA probe technique. The biopsies were processed both for RT-PCR and ISH. We also investigated a model for bacterial induced MMP expression in human gingival fibroblasts (HGF) infected by Eikenella corrodens. RESULTS: We found an expression of the mRNA encoding MMP-1 only in diseased gingiva but at low levels relative to beta-actin (mean+/-SD: diseased versus healthy: 0.013+/-0.024 versus 0). Although the frequencies and levels of mRNA encoding for MMP-2 or MT1-MMP are not significantly different between each group (mean+/-SD: 0.329+/-0.344 versus 0.137+/-0.219 for MMP-2; 0.485+/-0.374 versus 0.466+/-0.296 for MT1-MMP), using ISH, we observed an expression of both mRNAs in fibroblasts of pathological specimens at sites that histologically showed signs of chronic inflammation and connective tissue remodelling. In vitro infection of HGF by Eikenella corrodens stimulated 3-fold the production of the mRNA encoding MMP-2 while other mRNAs remained unchanged. CONCLUSION: Our results did not reveal significant differences in the expression of mRNAs encoding for the MMPs between healthy and periodontitis-affected patients, reflecting the great heterogeneity in the periodontal status of individuals. However, they indicate that gingival fibroblasts are an active source of MMP-2 production in response to a periopathogen.

Adolescent↗
PubMed2001

Down-Regulation of MT1-MMP expression by the alpha3 chain of type IV collagen inhibits bronchial tumor cell line invasion.

The basement membrane (BM) is the first barrier encountered by tumor cells when they become invasive. Moreover, some invasive tumor clusters are surrounded by a remnant or neosynthetized BM material. We have previously reported the presence of a particular alpha chain of type IV collagen, the alpha3(IV) chain, in bronchopulmonary carcinomas. This chain was not detected in the normal bronchial epithelium, but was found around some invasive tumor cluster BM. In the present study, we examined the effects of the alpha3(IV) chain on the invasive properties of bronchial tumor cell lines, with special emphasis on their expression of matrix metalloproteinase-2 (MMP-2) and its activator, membrane type 1-matrix metalloproteinase (MT1-MMP), which is largely involved in tumor progression. Two epithelial bronchial cell lines (16HBE14o- and BZR), showing different invasive abilities, were evaluated. Using the Boyden chamber invasion assay, we demonstrated that the alpha3(IV) chain inhibits the invasive properties of BZR cells and modifies their morphology by inducing an epithelial cell shape. In the presence of the recombinant NC1 domain of the alpha3(IV) chain, the expression of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) was not modified in either cell line. The NC1 alpha3(IV) domain did not modulate the MT1-MMP expression of noninvasive 16HBE14o- cells, whereas a 50% decrease of MT1-MMP mRNA was observed in invasive BZR cells. Accordingly, Western blot analyses showed a disappearance of the 45-kd MT1-MMP form when BZR cells were treated with the recombinant NC1 alpha3(IV) domain. These findings suggest that the alpha3 chain of type IV collagen may play a role in tumor invasion, at least by decreasing the expression and synthesis of MT1-MMP.

Bronchi↗