Multicentre randomised phase II trial of gemcitabine+platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2.

Aim: To investigate the efficacy and safety of gemcitabine and platinum salt, with or without trastuzumab, in patients with locally advanced or metastatic urothelial carcinoma overexpressing Her2.

Methods: The main eligibility criterion was Her2 overexpression on immunohistochemistry (IHC 2+ or 3+) of primary tumour tissue confirmed by fluorescence in situ hybridisation (FISH). Patients were randomised to Arm A: gemcitabine 1000mg/m(2) (days 1 and 8) plus either cisplatin (70mg/m(2)) or carboplatin (AUC=5) (day 1 every 3 weeks) or Arm B: added trastuzumab (8mg/kg loading dose, then 6 mg/kg every 21 days until progression).

[Should we systematically screen for Lynch syndrome in patients with upper urinary tract carcinoma?].

Objective: The data describing the urologic extracolonic cancers associated with Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) are variable. The aim of our study was to establish the frequency of mutations in mismatch repair (MMR) genes in patients with upper urinary tract transitional cell carcinoma (UUT-TCC) and to evaluate the clinical benefits of a systematic screening.

Methods: Specimen blocks were obtained from 146 patients treated for UUT-TCC in our center.

Gene panel model predictive of outcome in patients with prostate cancer.

In men at high risk for prostate cancer, established clinical and pathological parameters provide only limited prognostic information. Here we analyzed a French cohort of 103 prostate cancer patients and developed a gene panel model predictive of outcome in this group of patients. The model comprised of a 15-gene TaqMan Low-Density Array (TLDA) card, with gene expressions compared to a standardized reference.

Hybrid oncocytic/chromophobe renal cell tumours do not display genomic features of chromophobe renal cell carcinomas.

Hybrid oncocytic/chromophobe tumours (HOCT) are renal tumours recently described displaying histological features of both renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), raising the question of their precise signification in the RO/ChRCC group. This study aimed to describe clinicopathological features of so called HOCT and to characterise their genomic profile. Five hundred and eighty-three tumours belonging to the ChRCC/RO group were retrospectively reviewed.

microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer.

The aim of this study was to evaluate the expression levels of microRNAs (miRNAs) in bladder tumors in order to identify miRNAs involved in bladder carcinogenesis with potential prognostic implications. Expression levels of miRNAs were assessed by quantitative real-time RT-PCR in 11 human normal bladder and 166 bladder tumor samples (86 non-muscle-invasive bladder cancer (NMIBC) and 80 muscle-invasive bladder cancer (MIBC)). The expression level of 804 miRNAs was initially measured in a well-defined series of seven NMIBC, MIBC and normal bladder samples (screening set).

SMARCB1/INI1 inactivation in renal medullary carcinoma.

Aims: Renal medullary carcinoma (RMC), a rare and highly aggressive tumour which occurs in patients with sickle-cell disease, shares many clinicopathological features with collecting duct carcinoma (CDC). The molecular mechanisms underlying RMC and CDC are mainly unknown, and there is ongoing debate about their status as distinct entities. Loss of expression of SMARCB1/INI1, a chromatin remodelling regulator and repressor of cyclin D1 transcription, has been reported recently in RMC.

A rare cause of hypertestosteronemia in a 68-year-old patient: a Leydig cell tumor due to a somatic GNAS (guanine nucleotide-binding protein, alpha-stimulating activity polypeptide 1)-activating mutation.

Leydig cell tumors of the testis are the most common type of non-germ cell testicular tumors. In adult patients, gynecomastia, oligozoospermia, erectile dysfunction, and other signs of feminization can be present, whereas testosterone levels are frequently in the normal range or slightly reduced. We describe a patient with a history of impaired sexual function, as well as progressive enlargement of the left testis, without gynecomastia.

Identification of CAD as an androgen receptor interactant and an early marker of prostate tumor recurrence.

Markers of prostate tumor recurrence after radical prostatectomy are lacking and highly demanded. The androgen receptor (AR) is a nuclear receptor that plays a pivotal role in normal and cancerous prostate tissue. AR interacts with a number of proteins modulating its stability, localization, and activity.

Clear-cell papillary renal cell carcinoma: 24 cases of a distinct low-grade renal tumour and a comparative genomic hybridization array study of seven cases.

Aims: To report clinicopathological and genomic characteristics of (ccpRCC), a rare, recently characterized renal tumour entity.

Methods And Results: Twenty-four renal tumours identified as ccpRCC were collected. Data from comparative genomic hybridization on microarrays (array-CGH) were obtained for seven of these.

Strength of molecular cytogenetic analyses for adjusting the diagnosis of renal cell carcinomas with both clear cells and papillary features: a study of three cases.

Histological features are usually sufficient for providing an accurate diagnosis of renal cell carcinomas (RCC). However, the morphological appearance might sometimes be misleading. For instance, RCC with papillary areas and extensive clear cell changes may be difficult to classify either as clear cell renal carcinoma or as papillary renal cell carcinoma (pRCC).

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

Background: 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.

Activation of the PI3K/AKT pathway induces urothelial carcinoma of the renal pelvis: identification in human tumors and confirmation in animal models.

Urothelial carcinoma of the renal pelvis is a deadly disease with an unclear tumorigenic mechanism. We conducted gene expression profiling on a set of human tumors of this type and identified a phosphatidylinositol 3-kinase (PI3K)/AKT activation expression signature in 76.9% (n = 13) of our samples.

Hybrid tumour 'oncocytoma-chromophobe renal cell carcinoma' of the kidney: a report of seven sporadic cases.

Objectives: To determine whether renal hybrid tumours (HT) appear as a specific clinical and radiological entity, as HT are characterized by the association of both oncocytes and chromophobe cells within the same tumour, and have been described in patients with oncocytosis and Birt-Hogg-Dube syndrome.

Patients And Methods: We reviewed the medical charts of 67 patients who had a partial or radical nephrectomy in our institution for renal oncocytoma (RO, 24), chromophobe renal cell carcinoma (CRCC, 36) and HT (seven), from January 2006 to October 2007. We report the clinical, radiological and pathological characteristics of the seven cases of HT.

[Juxtaglomerular cell tumors: report of two cases with genomic analysis].

Juxtaglomerular-cell tumor (JGCT), first described in 1967, is a rare tumor of the kidney that derives from specialized smooth-muscle cells of the wall of the glomerular afferent arteriole. Less than 100 cases have been published, mainly as single-case reports or small series. JGCTs are considered benign, but the clinical follow-up has been short in most reported cases.

[Evaluation of p63 and p504s markers for the diagnosis of prostate cancer].

Prostate cancer with 60,000 new cases a year is a public health problem which requires adapted and effective responses. The era of PSA screening dramatically increased the number of prostate biopsies that pathologists have to screen and consequently the number of difficult cases requiring analysis. Immunohistochemistry with anti-AMACR/p504s is useful for detecting prostate cancer in the full range of prostate specimens encountered in needle biopsies.

[Non clear cell renal cell carcinoma. 2008 update in renal tumor pathology].

Non clear cell renal cell carcinomas represent almost 20% of all renal neoplasms. Their classification is continuously being adjusted according to new cytogenetic and molecular data. Since molecular techniques are expensive, diagnosis still relies on morphological and immuno-histochemical criteria detailed hereby.

Tubulocystic carcinoma of the kidney: clinicopathologic analysis of 31 cases of a distinctive rare subtype of renal cell carcinoma.

A distinctive tumor described under the terms Bellini duct carcinoma and low-grade collecting duct carcinoma has been referred to by us and others as tubulocystic carcinoma. This renal cell carcinoma subtype is not recognized in the World Health Organization 2004 classification. Herein, we present a detailed study of 31 cases to further characterize this rare subtype of renal cell carcinoma.

The prognostic value of vascular endothelial growth factor (VEGF)-A and its receptor in clinically localized prostate cancer: a prospective evaluation in 100 patients undergoing radical prostatectomy.

Objectives: To study the prognostic value of vascular endothelial growth factor (VEGF)-A and its receptor VEGFR-1 in localized prostate cancer.

Methods: One hundred patients undergoing radical prostatectomy (RP) for clinically localized prostate cancer were prospectively included. Plasma levels of VEGF-A were measured preoperatively.

Somatic pairing of chromosome 19 in renal oncocytoma is associated with deregulated EGLN2-mediated [corrected] oxygen-sensing response.

Chromosomal abnormalities, such as structural and numerical abnormalities, are a common occurrence in cancer. The close association of homologous chromosomes during interphase, a phenomenon termed somatic chromosome pairing, has been observed in cancerous cells, but the functional consequences of somatic pairing have not been established. Gene expression profiling studies revealed that somatic pairing of chromosome 19 is a recurrent chromosomal abnormality in renal oncocytoma, a neoplasia of the adult kidney.

Large-scale real-time reverse transcription-PCR approach of angiogenic pathways in human transitional cell carcinoma of the bladder: identification of VEGFA as a major independent prognostic marker.

Background: Actors of the angiogenesis pathways are targets for the new promising targeted therapies already used in several malignancies. In bladder cancer, antiangiogenic molecules could also add to already existing treatment options.

Objective: To evaluate the involvement of angiogenesis pathways in bladder carcinogenesis and identify new molecular markers having a clinical implication.

Gene expression study of Aurora-A reveals implication during bladder carcinogenesis and increasing values in invasive urothelial cancer.

Objectives: Urothelial carcinoma is a frequent and aggressive cancer. We wanted to gain better insight into the early molecular mechanisms of bladder carcinogenesis by evaluating Aurora-A gene expression, which is implicated in genomic stability and essential for mitosis.

Materials: This study, using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), analyzed the expression levels of three selected genes in dissected tissues from normal bladder, noninvasive cancers, and muscle-invasive bladder carcinomas (n = 49).

Renal translocation carcinomas: clinicopathologic, immunohistochemical, and gene expression profiling analysis of 31 cases with a review of the literature.

We report clinicopathologic features of a large series of renal translocation carcinomas from a multicentric study. Diagnosis was performed by cytogenetic examination of fresh material and/or by immunochemistry with antibodies directed against the C-terminal part of transcription factor E3 (TFE3) and native transcription factor EB (TFEB) proteins. Clinical data, follow-up, and histologic features were assessed.

Loss of chromosomes 9 and 11 may be recurrent chromosome imbalances in juxtaglomerular cell tumors.

Juxtaglomerular cell tumor (JGCT), first described in 1967, is a rare tumor of the kidney that derived from specialized smooth muscle cells of the wall of the glomerular afferent arteriole. Less than 100 cases have been published, mainly as isolated case reports or small series. JGCTs are considered benign, but the clinical follow-up is short in most reported cases.

The association of vascular endothelial growth factor receptor-1 with the risk of cancer progression following radical prostatectomy.

In the current study, we analysed the prognostic value of vascular endothelial growth factor receptor-1 (VEGFR-1) in clinically-localized prostate cancer (PCa). Forty patients who had undergone radical prostatectomy (RP) for clinically-localized PCa were included. Two groups were compared: 17 patients who experienced cancer progression following RP (group 1) and 23 patients who remained free of recurrence after intervention (group 2).