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Vincent Molinié

Publications and source records attributed to Vincent Molinié.

At least 19 recordsLinked to original sources
PubMed2006

Development of a seeded scaffold in the great omentum: feasibility of an in vivo bioreactor for bladder tissue engineering.

OBJECTIVES: Tissue engineering is very promising in bladder reconstruction. However, one of the main problems is to limit the development of ischaemic fibrosis during tissue maturation. We describe a model using the omentum as an in vivo bioreactor for a previously seeded scaffold. METHODS: Bladder biopsies were taken from five female pigs, from which both urothelial and smooth muscle cells cultures were made. These cultured cells were used to seed a sphere-shaped small intestinal submucosa (SIS) matrix, which was transferred into the omentum after 3 wk of cell growth. The grafts were harvested 3 wk later and histologic, immunohistochemical, and functional studies were performed. RESULTS: We obtained a highly vascularized tissue-engineered construct that contracted in response to acetylcholine stimulation. The wall thickness was 4mm, on average. Histologic and immunostaining analysis of the construct confirmed the presence of a multilayer urothelium on the luminal aspect and deeper fascicles organised tissue composed of differentiated smooth muscle cells and mature fibroblasts without evidence of inflammation or necrosis. Large- and small-diameter vessels were clearly identified histologically in the tissue obtained. CONCLUSION: The omentum permitted in vivo maturation of seeded scaffolds with the development of a dense vascularisation that is anticipated to prevent fibrosis and loss of contractility. This in vivo maturation into the omentum could be the first step before in situ implantation of the construct.

Animals↗
PubMed2006

HSP90 expression: a new predictive factor for BCG response in stage Ta-T1 grade 3 bladder tumours.

OBJECTIVES: Although Bacillus Calmette-Guérin (BCG) instillations are considered as the adjuvant treatment of choice for stage Ta-T1 grade G3 bladder tumours, there is no consensus for a predictive factor to assess BCG success. This study attempted to evaluate if heat shock proteins (HSPs) could be useful predictive markers in BCG responses. METHODS: Thirty-three primary resected G3 superficial bladder tumours were included in the study. All patients received adjuvant BCG instillations. The mean follow-up was 56 mo (range: 24-132 mo). HSP expression was evaluated by immunochemistry. RESULTS: In the 33 patients, 18 had no recurrence (group 1), 9 had recurrence with no muscular invasion (group 2), and 6 had an invasive recurrence (group 3). A significant correlation was found between lack of expression of HSP90 and BCG response: the mean HSP expression was 92.7%, 84.4%, and 26.7% for groups 1, 2 and 3 tumours, respectively (p<0.0001). For the 6 patients who did not positively respond to BCG, HSP expression was <40%. All the tumours with a HSP90 expression >40% positively responded to BCG, corresponding to group 1 or 2 patients. In contrast, HSP60 expression was not correlated to the BCG response. CONCLUSIONS: HSP90 could be considered as a very promising marker to assess BCG treatment response. Low HSP90 expression (<40%) could be useful to predict BCG failure and early stage cystectomy could be proposed for these selected patients with primary high-risk grade 3 superficial bladder tumours.

Adjuvants, Immunologic↗
PubMed2006

Should bladder biopsies be performed routinely after bacillus Calmette-Guérin treatment for high-risk superficial transitional cell cancer of the bladder?

OBJECTIVE: After endoscopic resection of high-grade superficial urothelial neoplasms (Ta, T1 or Tis), adjuvant bacillus Calmette-Guérin (BCG) therapy is performed routinely to avoid recurrence and/or progression. Vesical biopsies often are performed to assess the efficacy of treatment. The aim of our study was to evaluate the usefulness of these biopsies. MATERIALS AND METHODS: During this retrospective bi-centre study, 130 patients who had undergone vesical high-grade tumour resection were included. There were 40 Ta associated with Tis in three cases, 87 T1 associated with Tis in 13 cases, and three isolated Tis. After BCG treatment, the following parameters were studied: cytoscopic findings, urine cytology and the histologic results of systematised biopsies. RESULTS: Urine cytology was positive (high-grade) for 26 patients and negative (normal or low-grade) for 104 patients. For the 26 patients with positive cytology, vesical flexible cystoscopy findings were considered suspicious in 18 patients and normal in eight patients. As for the 104 patients who presented negative cytology, cystoscopic findings were considered negative in 76 patients and suspicious in 28 patients. In the present study, the sensitivity of cytology and cystoscopy in the detection of recurrence after BCG treatment was 56% and 87.5%, respectively; specificity was 56% and 81.6%, respectively. When the two examinations were combined, sensitivity was 100%, and specificity was 76%. CONCLUSIONS: After BCG therapy, the association of negative flexible cystoscopy findings and normal urine cytology made it possible to avoid routine biopsies. Patients could therefore avoid the morbidity of this procedure.

BCG Vaccine↗
PubMed2006

Is quantitative real-time RT-PCR an adjunct to immunohistochemistry for the evaluation of ErbB2 status in transitional carcinoma of the bladder?

OBJECTIVE: To test different approaches of evaluation of the ErbB2 status in a large series of human transitional cell carcinoma (TCC) of the bladder with the prospect of finding targeted therapies. METHODS: ErbB2 status of 73 human TCC samples was analyzed by both immunohistochemistry (IHC) and by quantification of mRNA levels of expression using real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, 18 bladder samples were studied for ERBB2 gene amplification by real-time quantitative PCR. RESULTS: Twenty-five tumors (34.2%) overexpressed ERBB2 mRNA compared to normal bladder samples; this alteration appeared in low-grade and low-stage tumors (pTaG1). Twenty-four (32.9%) tumors showed moderate (++) or strong (+++) immunostaining. A very strong agreement was found between the two methods (kappa = 0.97, 95% confidence interval, 0.90-1). ErbB2 status was not associated with tumor stage. Of the 18 bladder samples tested for ERBB2 gene amplification, only one showed ERBB2 DNA amplification. CONCLUSIONS: ErbB2 overexpression occurs in about one third of bladder TCCs. This overexpression can be detected by RT-PCR with a very good correlation with IHC. RT-PCR can therefore be used for cases considered doubtful on IHC rather than gene amplification studies because, in TCC, gene amplification is not the predominant mechanism of both mRNA and protein overexpression. Accurate quantification of ErbB2 status is mandatory for the use of anti-ErbB2-targeted therapies in bladder TCC.

Adult↗
PubMed2006

Alpha-methyl CoA racemase expression in renal cell carcinomas.

Alpha-methyl CoA racemase (AMACR), a new molecular marker for prostate cancer, has been recently reported to be one of the most highly expressed genes in papillary renal cell carcinomas (RCCs). We tested the diagnostic usefulness of AMACR antibody in a series of 110 renal tumors: 53 papillary RCCs (33 type 1, 20 type 2); 25 conventional RCCs; 6 chromophobe RCCs; 9 oncocytomas; 5 mucinous tubular and spindle tumors; 2 urothelial carcinomas; 7 angiomyolipomas; and 2 Bellini carcinomas. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections, with a primary prediluted rabbit monoclonal anti-AMACR antibody. Both type 1 and type 2 papillary RCCs exhibited cytoplasmic immunoreactivity for AMACR, with diffuse strong granular staining in 96.4% (53/55) of tumors, without correlation with type or nuclear grade. The 5 mucinous, tubular, and spindle cell carcinomas strongly expressed AMACR, and only 5 of 25 clear cell RCCs and 1 of 9 oncocytomas were focally reactive. The remaining 6 chromophobe RCCs, 5 urothelial carcinomas, and Bellini duct carcinomas showed no immunoreactivity for AMACR. Because high expression of AMACR is found in papillary RCCs (type 1 and 2) and in mucinous, tubular, and spindle cell carcinomas of the kidney, immunostaining for AMACR should be used in conjunction with other markers when histological typing of a renal tumor is difficult.

Adenocarcinoma, Mucinous↗
PubMed2006

Diagnostic utility of a p63/alpha-methyl coenzyme A racemase (p504s) cocktail in ambiguous lesions of the prostate upon needle biopsy.

OBJECTIVE: To investigate the potential utility of a new combined immunostaining technique for diagnosing prostate cancer from histological analysis of needle biopsy specimens. MATERIALS AND METHODS: Tissue was immunostained with a combination of antibodies against a basal cell marker (p63), and an enzyme commonly overexpressed in prostate cancer (p504s), on 63 small prostate cancer foci (<1 mm) and 109 cases of ambiguous lesions observed in needle biopsies. RESULTS: After p63/p504s immunostaining, 93% of the ambiguous lesions (102/109) were classified. The final diagnoses retained were: 92 prostate cancers, seven atypical small acinar proliferations suspected of being malignant but undiagnosed, 21 prostatic intraepithelial neoplasia, five atypical adenomatous hyperplasia, and 36 atrophic benign mimickers of cancer. CONCLUSIONS: Combining p504s as a positive marker for prostate cancer and p63 as a negative marker might improve diagnostic performance, sensitivity and specificity, and lead to fewer false-negative results. This simple immunostaining procedure should reduce the percentage of residual ambiguous lesions and the need for additional biopsies.

Antibodies↗
PubMed2005

Characterization of quantitative chromosomal abnormalities in renal cell carcinomas by interphase four-color fluorescence in situ hybridization.

Renal cell carcinomas (RCC) in adults are histologically heterogeneous solid tumors with specific chromosomal abnormality patterns included in the World Health Organization (WHO) classification. To overcome some of the drawbacks of cytogenetic and comparative genomic hybridization (CGH) analyses, we designed a first-generation cytogenetic diagnostic test using four-color fluorescence in situ hybridization (FISH) on interphase nuclei. We selected 51 bacterial artificial chromosome and P1-derived artificial chromosome clones covering 17 chromosomal regions involved in the abnormalities of the adult RCC histologic subtypes. An initial set of probes allowed the identification of clear-cell RCC, papillary RCC, and other RCC on a single slide. A second test allowed the detection of additional chromosomal abnormalities or aberrations specific to chromophobic RCC and oncocytomas. We tested 25 cases of RCC, and the results were in agreement with those of cytogenetic techniques and/or CGH methods. The techniques appeared to be very sensitive, because small tumoral cell clones that were undetected by other cytogenetic methods were identified with this method. It was concluded that the multicolor FISH test was specific and sensitive, easy to perform, and could be part of the investigation process in RCC.

Adult↗
PubMed2005

Multicenter determination of optimal interobserver agreement using the Fuhrman grading system for renal cell carcinoma: Assessment of 241 patients with > 15-year follow-up.

BACKGROUND: The Fuhrman system is the most widely used nuclear grading system for renal cell carcinoma (RCC). Although Fuhrman nuclear grade is widely accepted as a significant prognostic factor, its reproducibility, as reported in the limited number of series available in the literature, appears to be low. METHODS: Between 1980 and 1990, 255 cases of RCC (pT1-3bN0M0) were treated with radical nephrectomy at the Department of Urology, University Hospital, Strasbourg, France. In a retrospective multicenter study, 3 pathologists independently classified 241 of these 255 cases according to the Fuhrman grading system. The authors searched for optimal interobserver agreement by collapsing the grading system to a three-tiered scheme and then to a two-tiered scheme. In addition, overall survival curves were generated according to the classic four-tiered scheme and also according to the best collapsed scheme. The kappa index was used to assess the level of agreement between each pair of observers, and the Cox model was used for multivariate survival analyses. RESULTS: The mean interobserver kappa value was 0.22 (range, 0.09-0.36). The best concordance was obtained by collapsing to a system in which low-grade (Grade 1-2) disease was compared with high-grade (Grade 3-4) disease. Doing so improved the mean interobserver kappa value to 0.44 (range, 0.32-0.55). Fuhrman grade was an independent prognostic factor for all 3 pathologists (P = 0.01, P < 0.0001, and P = 0.004, respectively), and nuclear grade continued to have independent prognostic value after the optimal collapsing algorithm was performed (P = 0.004, P = 0.0003, and P = 0.005). CONCLUSIONS: Collapsing of the Fuhrman grading system to a two-tiered scheme led to an improvement in interobserver agreement while preserving the independent prognostic value of nuclear grade.

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↗
PubMed2005

Effects of long-term finasteride treatment on prostate cancer morphology and clinical outcome.

OBJECTIVES: To examine the morphologic alterations of finasteride therapy on prostate cancer compared with no treatment or treatment with a luteinizing hormone-releasing hormone (LHRH) agonist and the clinical outcomes of patients treated with finasteride. METHODS: The data of 56 patients with prostate cancer who had taken finasteride for at least 6 months were reviewed. A central pathology review was performed in a blinded manner comparing these patients with 56 matched controls and 44 patients who received a 3-month course of LHRH agonist before radical prostatectomy. The histologic hormonal treatment effects included apoptosis, vacuolated cytoplasm, pyknotic nuclei, and small irregular glands. An overall consensus was scored using a three-tiered system: no apparent effect (score = 0), suspicious for hormonal effect (score = 1), and highly suggestive of hormonal treatment (score = 2). A Gleason score was assigned to all prostatectomy specimens. RESULTS: The mean hormonal treatment score for the prostatectomy specimens was 0.4, 0.5, and 1.6 for the control, finasteride, and 3-month LHRH groups, respectively. Surprisingly, 20% of control patients had suspicious or highly suggestive hormonal effects and 26% of the finasteride-treated patients did so. For the LHRH-treated group, only 23% did not demonstrate classic features of hormonal treatment. Similar clinical outcomes were observed between the finasteride and control groups. CONCLUSIONS: No consistent hormonal therapy effects with finasteride treatment were observed compared with LHRH agonists. The hormonal effect was observed in the control group. Therefore, although other aspects of the Prostate Cancer Prevention Trial design might account for the greater percentage of Gleason grade tumors in the study arm, morphologic changes due to long-term finasteride treatment were not a likely cause.

Adult↗
PubMed2005

[Is tumour grade applicable to finasteride-treated prostate cancer?].

The treatment of prostate cancer by endocrine therapy induces histological changes of benign or malignant prostate glands. Treated cancers often have a more suspicious architecture, resulting in a higher Gleason score, while their nuclear grade (WHO) appears to be more reliable due to a reduction of the size of nuclei. Most authors appear to agree that cancers discovered by biopsy in patients treated with endocrine therapy should not be graded. A review of the literature appears to indicate that finasteride has less marked histomorphological consequences than other hormone-suppressor treatments and could have a lesser effect on the Gleason score. This paper, based on a review of the literature on this subject, emphasizes: (1) the extent of histological changes after androgen deprivation endocrine therapy; (2) histological changes after Finasteride and the difficulties of histological interpretation, particularly the risk of overestimating the Gleason histoprognostic score; (3) the need for urologists to indicate any treatment by 5-alpha-reductase inhibitors or androgen deprivation when requesting histological examination; (4) the value of collecting and documenting cases observed in the Uropathology Club in collaboration with the Oncology committee of the Association Française d'Urologie.

5-alpha Reductase Inhibitors↗
PubMed2005

[Value of new prostate cancer markers: alpha methylacyl CoA racemase (P504S) and p63].

The diagnosis of prostate cancer is based on histological examination of prostatic biopsies using histological criteria identified on standard stains. In certain lesions mimicking prostate cancer, the pathologist must perform immunohistochemical studies looking for loss of basal cells and antibodies directed against cytokeratin CK 903 (34bE12) or CK5/6, which sometimes give inconclusive results leading to a diagnosis of suspicious site. The discovery of overexpression of alpha-méthylacyl CoA racemase in prostate cancer using a microarray technique has allowed the development and marketing of an antibody (P504S /AMACR) which, in combination with a new basal cell marker (p63), is a very valuable tool for the pathologist in the management of suspicious sites and cancers less than 1 mm in diameter detected on prostatic biopsies.

Humans↗
PubMed2004

Evaluation of imaging-guided fine-needle percutaneous biopsy of renal masses.

To evaluate the utility of imaging-guided fine-needle percutaneous biopsy of renal masses, we conducted a prospective analysis of our imaging-guided procedures from January 1999 to February 2003. We performed 54 percutaneous core biopsies in 46 patients. Fluoro-computed tomography and ultrasound guidance were respectively used in 48 and six cases. One to four specimens were obtained by using an 18-gauge automated coaxial biopsy system. We reviewed the patients medical records, pathology results, and imaging studies. Core biopsy results were compared with surgical pathology (n=27) or clinical follow-up (n=19). All biopsies provided sufficient material for analysis. The mean tumor size was 33 mm. Biopsy findings were positive for malignancy in 31 cases; histologic diagnoses included renal cell carcinoma (n=23), transitional cell carcinoma (n=5), and metastasis (n=3). Biopsy revealed 15 benign diagnoses: oncocytoma (n=6), hemorrhagic renal cyst (n=3), chronic nephritis (n=3), angiomyolipoma (n=2), and mycotic renal abscess (n=1). The average follow-up period for patients with benign diagnoses was 16 months. Biopsy results showed normal renal parenchyma in eight of 54 procedures, all of which had recuperated by subsequent biopsies. No immediate complications occurred after the procedures. Imaging-guided percutaneous core biopsy is a safe and accurate method for the evaluation of renal masses.

Adult↗
PubMed2004

[Value of the antibody cocktail anti p63 + anti p504s for the diagnosis of prostatic cancer].

UNLABELLED: Numerous lesions of the prostate, such as atrophy, adenomatous atypical hyperplasia (adenosis) or PIN can be misdiagnosed with prostatic cancer, and confused with ASAP, leading to perform additional biopsies. In such lesions, the pathologist can perform an immunohistochemical study with the anti-high molecular weight cytokeratin antibody CK903 (34bE12), which confirms the absence of basal cells and supports the diagnosis of prostatic cancer. AIM OF THE STUDY: To compare markers of basal cells (cytokeratin 5/6, p63) and the marker of prostatic carcinomatous glands (p504s) or alpha methylacyl-CoA racemase (AMACR). MATERIAL AND METHODS: Retrospective study of 44 cases of paraffin-embedded prostatic specimens (36 biopsies, 4 PER, 1 adenomectomy and 3 radical prostatectomies), consisting in 20 cases of prostatic carcinomas (2 intraductal, 12 Gleason 6 (3+3), 4 Gleason 7 (4+3), 2 Gleason 8 (4+4)), 11 ASAP, 9 PIN (2 low grade, 7 high grade (2 isolated)), and 10 benign lesions (8 atrophy, 1 atypical adenomatous hyperplasia and 1 case of clear cell cribriform hyperplasia). All cases were tested with antibodies to CK 5/6, and with a cocktail to p63 and p504s, after heat antigenic retrieval on NEXES Ventana processor. RESULTS: Basal cells of normal prostatic glands stained with CK5/6 and p63 in 91,3% and 100% of cases, independently from the fixation procedure (Bouin or Formalin). Carcinomas had a p63-/p504s+ profile, PIN were p63+/p504s+, and benign lesions were p63+/p504s-. We observed an increase in sensitivity: p63/p504s (100%), CK5/6 (80%), p63 (90%), p504s (95%), and specificity: p53/p504s (90%), CK5/6 (87.5%), p63 (90.5%), p504s (90.9%). CONCLUSION: Our results show that the use of a cocktail to p63/p504s is more specific than the use of CK5/6 alone this technique supports a diagnosis of prostatic cancer in 40% of cases previously considered as ASAP.

Antibodies↗
PubMed2004

[Immunohistochemical characterisation of the main histologic subtypes of epithelial renal tumours on tissue-microarrays. Study of 310 cases].

OBJECTIVE: Diagnosis of renal epithelial tumours of adult is often easily made. Nevertheless, it can be difficult to distinguish clear cell carcinoma (CCC) and chromophobe carcinoma (CCHRO), or the eosinophilic variants of CCC and CCHRO with papillary carcinoma (CTP) and oncocytoma (ONCO). The objective is to study and validate immunohistochemical phenotypes of these tumours and to evaluate if they are helpful and to define a diagnostic strategy. MATERIALS AND METHODS: 310 tumours (75 CCC, 89 CTP, 50 CCHRO and 96 ONCO) were collected and put on 4 tissue-arrays blocks. Immunohistochemical stainings were performed with some usual antibodies: pancytokeratin AE1-AE3, EMA, vimentin, CD10, CK7, CK20 and RCC (Renal Cell Carcinoma). RESULTS: Pancytokeratin AE1-AE3 is expressed mainly in CTP (82.5%). The cytoplasmic staining of EMA is seen in almost all CCHRO (98%) and more than half of CTP (57%). Vimentin is rather specific of CCC (54.5%) and CTP (85%) whereas it is negative in ONCO and CCHRO. CD10 is expressed in the majority of CCC (86.5%) and in some of CTP and CCHRO 65 and 39% respectively. CK7 is rather specific of CTP and CCHRO with 79 and 81.5% of positivity rate. Based on statistical analysis, we have built a diagnostical tree allowing to distinguish 79% of tumours using only three antibodies: CK7, vimentin and CD10. CONCLUSION: CCC are CK7-/Vim-/CD10+ or CK7-/Vim+; CTP are CK7+/Vim+; CCHRO are CK7+/Vim-; and ONCO CK7-/Vim-/CD10-. In the oncocytoma/chromophobe group, ONCO are more often CK7-/EMA- and CCHRO CK7+/EMA+.

Adenoma, Oxyphilic↗
PubMed2004

Diagnostic utility of a p63/alpha-methyl-CoA-racemase (p504s) cocktail in atypical foci in the prostate.

Prostatic needle biopsy is the preferred method for diagnosing early prostate cancer, providing specific information. In cases of histological cancer mimics, a diagnosis of atypical small acinar proliferation suspected of but not diagnosed as malignancy can be made. In such cases, and in small focus carcinomas, pathologists use 34betaE12, cytokeratin (CK) 5/6 or p63 immunostaining to label basal cells, and alpha-methylacyl-CoA racemase (AMACR/p504s) immunostaining as a positive prostate cancer marker on two distinct slides. However, in cases of small foci, ambiguous lesions might disappear. The purpose of our study was to improve the sensitivity of a cocktail of two antibodies (p63/p504s) with a sample incubation on 260 prostatic specimens, in order to help make a decision in conjunction with standard histology and CK 5/6 immunostaining. We tested 101 small focus prostatic cancers, 104 atypical small acinar proliferation, 19 high-grade prostatic intraepithelial neoplasia, two atypical adenomatous hyperplasia and 34 benign mimics of cancer. After p63/p504s immunostaining, the final diagnoses retained were as follows: 154 prostatic cancers, 14 atypical small acinar proliferation, 30 high-grade prostatic intraepithelial neoplasia, three atypical adenomatous hyperplasia and 62 benign mimics of cancer. To differentiate malignant from benign lesions, we used the criteria of greater sensitivity to p504s/p63 (95%) than to CK 5/6 (57%) or p63 (86%), and higher specificity for p504s/p63 (95%) than for CK 5/6 (88%) or p63 (81%). With the p504s/p63 cocktail, 89% of the ambiguous lesions were classified vs 53% for CK 5/6. Combined use of the two antibodies, one (p504s) as a positive marker and the other (p63) as a negative marker, with a simple immunostaining procedure, may improve diagnostic performance, sensitivity and specificity, leading to a reduction in the risk of false negatives; this technique in cases of atypical small acinar proliferation should reduce the percentage of residual ambiguous lesions and the need for additional biopsies.

Biopsy, Needle↗