Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma

<p>Abstract</p> <p>Background</p> <p>Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC.</p> <p>Methods</p> <p>Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors.</p> <p>Results</p> <p>A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities.</p> <p>Conclusions</p> <p>Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.</p

Evaluation of diffusion weighted imaging in the context of multi-parametric MRI of the prostate in the assessment of suspected low volume prostatic carcinoma

Data from a multi-parameteric MRI study of patients with possible early-stage prostate cancer was assessed with a view to creating an efficient clinical protocol. Based on a correlation analysis suggesting that diffusion-weighted imaging (DWI) scores are more strongly correlated with overall PIRADS scores than other modalities such as dynamic contrast enhanced imaging or spectroscopy, we investigate the combination of T2-weighted imaging (T2w) and DWI as a potential diagnostic tool for prostate cancer detection, staging and guided biopsies. Quantification of the noise floor in the DWI images and careful fitting of the data suggests that the mono-exponential model provides a very good fit to the data and there is no evidence of non-Guassian diffusion for b-values up to 1000 s/mm2. This precludes the use of kurtosis or other non-Gaussian measures as a biomarker for prostate cancer in our case. However, the ADC scores for healthy and probably malignant regions are significantly lower for the latter in all 20 but one patient. The results suggest that a simplified mp-MRI protocol combining T2w and DWI may be a good compromise for a cost and time efficient, early-stage prostate cancer diagnostic programme, combining robust MR biomarkers for prostate cancer that can be reliably quantified and appear well-suited for general clinical practice

Expression of NRG1 and its receptors in human bladder cancer

BACKGROUND: Therapies targeting ERBB2 have shown success in the clinic. However, response is not determined solely by expression of ERBB2. Levels of ERBB3, its preferred heterodimerisation partner and ERBB ligands may also have a role. METHODS: We measured NRG1 expression by real-time quantitative RT–PCR and ERBB receptors by western blotting and immunohistochemistry in bladder tumours and cell lines. RESULTS: NRG1a and NRG1b showed significant coordinate expression. NRG1b was upregulated in 78 % of cell lines. In tumours, there was a greater range of expression with a trend towards increased NRG1a with higher stage and grade. Increased expression o

ESUR prostate MR guidelines 2012

The aim was to develop clinical guidelines for multi-parametric MRI of the prostate by a group of prostate MRI experts from the European Society of Urogenital Radiology (ESUR), based on literature evidence and consensus expert opinion. True evidence-based guidelines could not be formulated, but a compromise, reflected by “minimal” and “optimal” requirements has been made. The scope of these ESUR guidelines is to promulgate high quality MRI in acquisition and evaluation with the correct indications for prostate cancer across the whole of Europe and eventually outside Europe. The guidelines for the optimal technique and three protocols for “detection”, “staging” and “node and bone” are presented. The use of endorectal coil vs. pelvic phased array coil and 1.5 vs. 3 T is discussed. Clinical indications and a PI-RADS classification for structured reporting are presented

TUMEURS TUBULO-PAPILLAIRES DU REIN (PLUSIEURS ENTITES CLINIQUES ET HISTOLOGIQUES DIFFERENTES ?)

PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Implications de la voie de signalisation ERBB dans la carcinogénèse urothéliale

Le cancer de la vessie, 5è cause de mortalité par cancer en France et 4è aux Etats-Unis, voit son incidence croître depuis 30 ans 1-3. Le carcinome à cellules transitionnelles, forme la plus fréquente des cancers de vessie, prédomine nettement chez l homme. Les tumeurs vésicales se répartissent en tumeurs superficielles (60 à 70 % des cas lors du diagnostic) et en tumeurs infiltrantes. Les tumeurs superficielles posent deux problèmes évolutifs différents mais pouvant s associer : le risque de récidive et/ou de progression. Les tumeurs superficielles sont cependant, dans l immense majorité des cas, accessibles à un traitement conservant la vessie 4, 5. Aux tumeurs superficielles on peut opposer les tumeurs infiltrantes de vessie. Celles-ci sont soit infiltrantes au moment du diagnostic (20 à 30 % des cas), soit résultent de l évolution vers l infiltration d une tumeurPARIS5-BU-Necker : Fermée (751152101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Utilisation du portfolio au cours du deuxième cycle des études médicales dans un service d’urologie

Objective : To introduce the use of a portfolio (PF) as a learning and evaluation tool for hospital medical students in a urology department. Methods : In the course of 6 consecutive 3-month sessions, 36 medical students each constituted a PF After having chosen a urological topic, each student identified his/her learning needs and constructed a PF by collecting various types of information (books, medical articles, internet, orals,...) with the aid of a tutor. The PF had to be established in the form of a series of questions asked by the student followed by answers provided by the information collected. The PF was scored (out of 20) and contributed to validation of the session. Students completed a satisfaction questionnaire. Results.- All students were validated (mean score: 14.2/20). Results of the satisfaction questionnaire showed that, although no student had previously performed a PF 27130 expressed the desire to establish a PF for another training attachment. This questionnaire also showed that the PF helps to improve theoretical knowledge (30136), the needs in relation to Professional practice (17136), the ability to select data (34136), and is a good self-learning tool (36136). The major difficulty encountered by students concerned sorting of data (26136) and written formulation of questions and answers (35136). Conclusion : The PF appears to be a good learning and evaluation tool that can be used in surgical training attachments. It guides students in their personal study and highlights the quality of their reasoning

Use of portfolios as a learning and assessment tool in a surgical practical session of urology during undergraduate medical training

We chose to introduce a portfolio as a learning and assessment tool in a practical training session of urological surgery for undergraduate medical students. Our primary objectives were to develop the students' self reflexive ability in front of complex medical cases and to teach them how to identify their learning needs in a short period of time, on a specific topic. Students completed, during their training session, a portfolio on a urological topic under the constant supervision of a tutor. The students were evaluated on their portfolio's presentation with a 20-point grade grid known in advance. Even in a surgical training session, a portfolio can be a useful learning and assessment tool. It clearly encourages self-reflection and pre-professional practice