Wild-type VHL Clear Cell Renal Cell Carcinomas Are a Distinct Clinical and Histologic Entity: A 10-Year Follow-up

International audienceBackground: Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with 50% risk of metastases at initial diagnosis or at follow-up. An inactivation of the tumor-suppressor gene von Hippel-Lindau (VHL) is present in >70% of sporadic cases by two of three different mechanisms: locus deletion, gene mutation, or promoter hypermethylation. Objective: To correlate the complete status of the VHL gene with clinical and pathologic criteria. Design, setting, and participants We retrospectively included 98 patients with ccRCC who underwent surgery between 2002 and 2005. VHL gene deletions (71 of 98; 72.4%), mutations (68 of 98; 69.4%), and promoter hypermethylations (13 of 98; 13.3%) were screened by gene copy analysis, gene sequencing, and methylation-specific multiplex ligation-dependent probe amplification, respectively. Outcome measurements and statistical analysis Relationships between VHL subgroups and the studied criteria were analyzed using chi-square and Student t tests. Survival was analyzed with the log-rank test and Kaplan-Meier curves. Results and limitations: Compared with ccRCCs with two events (66.3%), tumors with no or one genetic event (33.6%) were associated with a higher nuclear grade IV (p = 0.02), metastases (p = 0.04), sarcomatoid component (p = 0.01), dense lymphocyte infiltrate (p = 0.013), and vascular endothelial growth factor overexpression (>30%) (p = 0.003), which was also an independent factor after multivariate analysis. Furthermore, wild-type VHL tumors (no inactivating event, 11.2%) were associated with nodal involvement (p = 0.019), and patients with this type of tumor had a specific survival of 33 mo compared with patients with ccRCCs having one or two VHL inactivating events (107 mo; p = 0.016). The retrospective design with small number of wild-type tumors was a limitation of this work. Conclusions: This long-term study (10-yr clinical follow-up) confirms that ccRCCs with wild-type VHL are highly aggressive tumors that need to be formally identified. Patient summary Among activated VHL tumors, the wild-type subgroup defines an aggressive phenotype with worse survival rates, suggesting that these tumors must be more thoroughly screene

Implications des praticiens en odontologie dans la prévention et l'hygiène bucco-dentaire (étude basée sur une enquête épidémiologique)

MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Odontologie (341722110) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Le Rôle de l'odontologiste médico-légal à la lumière de l'I.R.C.G.N. (De la théorie à la pratique)

L'IRCGN est le laboratoire de police scientifique de la Gendarmerie Nationale française qui contribue dans le cadre d'enquétes judiciaires, à la révélation des preuves scientifiques et notamment l'identification de personnes retrouvées décédées suite à une disparition, à un crime ou suite à une catastrophe de masse. L'identification de ces victimes est une nécessité morale, légale et administrative pour l'établissement de l'acte de décès. Le rôle de l'odontologiste médico-légal est primordial au sein de l'équipe pluridisciplinaire d'identification humaine avec pour mission de comparer les odontogrammes post-mortem et ante-mortem dans un but d'identification. Par l'examen de la denture, et à la demande des enquêteurs, il s'attache à préciser, entre autre, l'origine humaine, l'âge, le sexe et l'origine ethnique. Par l'étude d'un cas, nous illustrons dans quelle mesure, les données dentaires apportent des informations pertinentes lors d'une reconstruction faciale. Quelques exemples d'identification médico-légale sont détaillés dans ce mémoire de thèse afin de montrer d'une part, le travail de l'odontologiste médico-légal, et de préciser d'autre part les motivations dans le choix des techniques utilisées au sein de l'IRCGN.The IRCGN is the lorensic laboratory of the French National Gendarmerie contributing through judicial surveys, the revelation of scientific evidence including identification of persons found dead after a disappearance, a crime or after mass disaster. The identification 01 these victims is a moral, legal and administrative setting the death certificate. The role 01 the dentist is crucial lorensic within the multidisciplinary team 01 human identification with the mission to compare odontograms post-mortem and ante-mortem identification purposes. By examination of the teeth, and at the request of investigators, he endeavors to clarify, among other things, human origin, age, sex and ethnicity. Through a case study, we illustrate how the dental data provide relevant information on a facial reconstruction. Sorne examples of forensic identification are detailed in this thesis to show the one hand, the work of forensic dentistry, and specify other motivations in the choice of techniques used in the IRCGN.MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Odontologie (341722110) / SudocSudocFranceF

Apport de l'odontologie au décryptage des gestes funéraires d’une sépulture collective : la grotte sépulcrale du Rhinocéros 4 (Commune de Péret, département de l'Herault)

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Apport de l'odontologie au décryptage des gestes funéraires d’une sépulture collective : la grotte sépulcrale du Rhinocéros 4 (Commune de Péret, département de l'Herault)

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Prise en charge du cancer du rein en 2007 : actualités et recommandations [Kidney cancer management in 2007: news and recommendations]

International audienceIn case of a single renal cell carcinoma strictly located in the kidney, the radical nephrectomy remains the treatment of choice. However, it has been estimated that nearly 30 to 40 % of renal cell carcinoma are about to recur after primitive surgery. In certain cases, conservative surgery can be discussed as an alternative to radical treatment, especially in case of exophytic renal tumour or less than 4 cm in diameter. New ablative techniques (radiofrequency and cryoablation) have shown promising results but the follow-up is still very limited. French national recommendation regarding kidney cancer have been updated in 2007 and following the development of clinical trials using antiangiogenic agents. Regarding the use of antiangiogenic agents, several points have to be taken into account: existence of renal cell carcinoma, presence of metastasis, number of metastasis, location and risk factor prognosis determination

Paraffin-embedded tissue is less accurate than frozen section analysis for determining VHL mutational status in sporadic renal cell carcinoma.

International audienceINTRODUCTION: Literature controversies exist regarding the prognostic value of VHL mutations. The objective was to compare paraffin-embedded and frozen section specimens for VHL mutations detection and to evaluate the reliability of DNA analysis in formalin-fixed tissues. METHODS: Seventy-six patients with clear cell renal cell carcinoma (RCC) previously assessed for VHL status from frozen samples were included. Seventy-three tumor samples were known to be mutated for VHL. DNA was extracted and an electrophoresis was performed to determine DNA quality. The whole coding sequence was synthesized by double PCR amplification followed by sequencing. Sequencing results were compared with those previously determined from frozen samples. RESULTS: DNA could be extracted from the 76 paraffin samples. DNA quality was highly degraded and significantly less amplified by PCR in 34.2%, resulting in no sequence available for analysis in 57.7% and discordance with frozen samples in 42.3% of the cases respectively. VHL mutations were found in 52.1% of the whole paraffin samples whereas 98% were mutated; 72% could be sequenced, resulting in 69.1% of VHL mutations in this subset. Only half of observed mutations were fully consistent with frozen analysis in the 3 exons. Neomutations were found in 10.5% and 28.9% of known mutations in frozen samples were not detected in paraffin blocks. Only DNA quality significantly influenced PCR amplification and sequencing. CONCLUSION: Tumoral DNA extraction and VHL mutation analysis can be performed from formalin-fixed paraffin-embedded (FFPE) tissue in RCC. But mutations identified tissues are not strictly concordant with those from frozen analysis and therefore results obtained from FFPE samples should be interpreted with care

Kystes atypiques et tumeurs kystiques du rein : considérations anatomopathologiques, radiologiques et chirurgicales. Conclusions du forum AFU 2007. [Atypical cysts and cystic tumours of the kidney: Histological, radiological and surgical considerations. Conclusions of the AFU 2007 forum.]

International audienceMalignant tumours may have a cystic appearance. They are dominated by multilocular cystic renal cell carcinoma, usually low-grade, which rarely metastasize. The Bosniak classification distinguishes non suspicious lesions (type I and II) from suspicious lesions (type III and IV) requiring resection and lesions requiring follow-up (type IIF). The main feature suggestive of malignancy is the enhancement of the septa and the walls of the cyst. Renal cysts classified as IIF require surveillance by contrast-enhanced imaging (CT, MRI or ultrasound). The treatment of cystic tumours is based on surgery. Partial nephrectomy is recommended in this type of tumour regardless of the size. Laparoscopy is a validated technique in experienced hands. Aspiration is not very effective for the treatment of benign cysts, but may be useful for diagnosis. Surgical resection of the roof of the cyst is the most effective technique

Loss of expression of TIMP3 in clear cell renal cell carcinoma.

International audienceAIMS: In clear cell renal cell carcinoma (CCRCC), vascular endothelial growth factor (VEGF) represents the central positive mediator of tumour angiogenesis while VEGF receptor (VEGFR) is the primary target of anti-angiogenic therapies. TIMP3 is a physiological VEGFR-2 antagonist and thus could be considered as an anti-angiogenic factor. We therefore determined the status of this physiological inhibitor in CCRCC. PATIENTS AND METHODS: Archival tumour from 105 patients was studied. TIMP3 expression was analysed using immuno-histochemistry and real-time RT-PCR. Results were correlated with clinicopathological variables. To analyse the mechanisms of gene silencing involved, we performed Multiplex Ligation-dependent Probe Amplification (MLPA) and methylation-specific MLPA (MS-MLPA). At last, we evaluated the main upstream pathway described implicating TGFbetaRII, which induces TIMP3 expression. RESULTS: A down-expression of TIMP3, determined by immunohistochemistry, affected 100/105 renal cancers (95.2%). TIMP3 mRNA levels were significantly lower in high-grade tumours. Loss of heterozygosity of the TIMP3 gene was observed in 8 tumours (7.6%) and the 5'CpG island of the TIMP3 promoter was found to be methylated in 25 tumours (23.8%). A down-expression of TGFbetaRII was found in 85/105 CCRCCs (80.9%). A significant correlation was found between TIMP3 expression and TGFbetaRII expression. CONCLUSIONS: This is the first demonstration that the loss of TIMP3 expression is observed in almost all CCRCCs. This loss of expression is a common molecular event in CCRCC. It may be an important initiation step for tumour development in a complex process implicating loss of heterozygosity on chromosome 22q, promoter hyper-methylation and inactivation of the TGFbetaRII pathway