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Background and Objective: Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high; therefore, it is essential to improve the selection and identification of at-risk patients to reduce mortality. The aim of the ANDROCAN study was to evaluate the biochemical recurrence (BCR) in patients with localized PCa treated by total prostatectomy at 5 yr after surgery, according to their presurgery gonadal status., Methods: A prospective cohort study was conducted including 1318 patients undergoing total prostatectomy for localized PCa with a 5-yr postoperative follow-up. Clinical and hormonal data (assays of total testosterone [TT], bioavailable testosterone [BT], dihydrotestosterone, estrone, and estradiol were performed by gas chromatography/mass spectrometry) as well as metabolic syndrome parameters were collected at baseline before surgery. Pathological data (predominant Gleason grade 4 and stage) were collected and cross-referenced centrally. Factors associated with BCR were assessed by a multivariate analysis, and BCR-free survival was assessed by a Kaplan-Meier analysis., Key Findings and Limitations: Among the 1318 patients, 237 had BCR of PCa. Considering demographic characteristics, populations with and without BCR were similar. However, patients with BCR had cancers with a higher Gleason score (p = 0.0001) and higher prostate-specific antigen (PSA) values (p = 0.0005) at baseline. Gleason score, pT >3a, and PSA level at baseline were positively correlated with BCR (p < 0.0001, p < 0.0001, and p = 0.0048, respectively), while BT and TT levels were not associated with BCR. This study includes patients with varying clinical characteristics, such as cancer history and metabolic syndrome, introducing variability that makes it challenging to isolate the specific effects of gonadal status on BCR. Another limitation is the lack of evaluation of long-term BCR beyond 5 yr, potentially overlooking recurrences that occur between 5 and 15 yr after surgery. This could lead to an underestimation of the actual long-term recurrence rates., Conclusions and Clinical Implications: Overall, PSA levels, high Gleason score, and pT >3a are associated with a greater likelihood of disease recurrence following initial treatment and could serve as important prognostic indicators for predicting the risk of BCR. In this prospective study, biochemical hypogonadism was not associated with a higher occurrence of BCR within 5 yr of prostatectomy. The biological gonadal status of preoperative patients could potentially be useful for therapeutic decisions but does not provide an indication for the oncological follow-up., Patient Summary: Five-year follow up of patients after surgery showed that there is no association between hypogonadism (low levels of total testosterone and bioavailable testosterone) and cancer recurrence. However, cancer recurrence seems to be more associated with aggressiveness of cancer at the time of detection., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive TFE3 fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required TFE3 FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The Gleason score is the most important prognostic marker for prostate cancer patients, but it suffers from significant observer variability. Artificial intelligence (AI) systems based on deep learning can achieve pathologist-level performance at Gleason grading. However, the performance of such systems can degrade in the presence of artifacts, foreign tissue, or other anomalies. Pathologists integrating their expertise with feedback from an AI system could result in a synergy that outperforms both the individual pathologist and the system. Despite the hype around AI assistance, existing literature on this topic within the pathology domain is limited. We investigated the value of AI assistance for grading prostate biopsies. A panel of 14 observers graded 160 biopsies with and without AI assistance. Using AI, the agreement of the panel with an expert reference standard increased significantly (quadratically weighted Cohen's kappa, 0.799 vs. 0.872; p = 0.019). On an external validation set of 87 cases, the panel showed a significant increase in agreement with a panel of international experts in prostate pathology (quadratically weighted Cohen's kappa, 0.733 vs. 0.786; p = 0.003). In both experiments, on a group-level, AI-assisted pathologists outperformed the unassisted pathologists and the standalone AI system. Our results show the potential of AI systems for Gleason grading, but more importantly, show the benefits of pathologist-AI synergy.

Background: There are no comparative data on pathological predictors at diagnosis, between African Caribbean and Caucasian men with prostate cancer (PCa), in equal-access centers. The objective of this study was to evaluate the grade groups of an African Caribbean cohort, newly diagnosed with PCa on prostate biopsy, compared with a Caucasian French Metropolitan cohort., Methods: A retrospective, a comparative study was conducted between 2008 and 2016 between the University Hospital of Martinique in the French Caribbean West Indies, and the Saint Joseph Hospital in Paris. Clinical, biological, and pathological data were collected at diagnosis. The primary outcome was the grade groups for Gleason score; the secondary outcome was the PCa detection rate. Multivariate analysis was performed using linear regression., Results: Of the 1880 consecutive prostate biopsy performed in the African Caribbean cohort, 945 had a diagnosis of PCa (50.3%) and 500 of 945 in the French cohort (33.8%). African Caribbean patients were older (mean 68.5 vs 67.5 years; P = .028), had worse clinical stage (13.2% vs 5.2% cT3-4; P < .001) and higher median prostate-specific antigen (PSA) level (9.23 vs 8.32 ng/mL; P = .019). On univariate analysis, African Caribbean patients had worse pathological grade groups than French patients (P < .001). Nevertheless, after adjustment on age, stage, and PSA, there were no significant differences between the two cohorts (P = .903)., Conclusion: African Caribbean patients presented higher PCa detection rate, and higher grade groups at diagnosis than French patients in equal-access centers on univariate analysis but not on multivariate analysis. African Caribbean patients with equivalent clinical and biological characteristics than Caucasian patients at diagnosis might expect the same prognosis for PCa., (© 2019 Wiley Periodicals, Inc.)

An association between HIV infection and cervical cancer, a major public health issue worldwide, has been reported. The aim of this study was to estimate the prevalence of human papillomavirus (HPV) infection and the distribution of HPV genotypes in HIV-infected women living in French Antilles and Guiana and to determine HIV-related characteristics associated with HPV infection. This cross-sectional study included 439 HIV-infected women who were followed between January 2011 and May 2014. Variables related to HIV infections were collected, and cervical samples were analysed to determine HPV genotypes. The median age of the population was 46 years. Estimated prevalence of HPV and high-risk (HR)-HPV infection were 50.1% IC95 [45.4-54.7] and 42% IC95 [37.3-46.6], respectively. HR-HPV 16, 52, 53 or intermediate risk-HPV-68 were found in 25% to 30% of the HPV-infected patients. Gynaecological screening revealed abnormal cervical smear in 24% and 42% of HR-HPV-negative and HPV-positive women, respectively (p = 0.003). Approximately 90% of women were on antiretroviral therapy (ART). Demographic characteristics associated with a higher prevalence of HPV infection included alcohol consumption. Regarding HIV-related characteristics, current therapy on ART, its duration, and undetectable plasma concentrations of RNA-HIV1 were associated with a lower risk of HPV infection. Infection rate with HR-HPV was higher than what is commonly reported in HIV-negative women worldwide and was more likely in women with incomplete HIV suppression. These results highlight the need for supporting adherence to ART, cervical cytology, HPV testing and HPV vaccination., Competing Interests: The authors have declared that no competing interests exist.

Aim: To assess the prognostic value of multiple recurrences on the risk of progression in a large cohort of TaG1 bladder cancer of low and intermediate risk based on the EORTC score and to evaluate prognostic factors of multiple recurrences., Materials and Methods: We retrospectively analyzed a French cohort of 470 patients with primary TaG1 bladder cancer diagnosed between 1986 and 2010 and followed until 2012. They were classified at low and intermediate risk using the EORTC risk score. Associations between the number of recurrences and the risk of progression to high grade Ta/T1 bladder cancer and progression to muscle-invasive disease were assessed. The characteristics of recurrences, as occurrence time or localization, and risk of other recurrences were evaluated., Results: Out of 470 patients, 251 had recurrence, 34 progressed to high grade Ta/T1 and 17 to muscle-invasive disease, including 4 who had non muscle-invasive progression first. The median follow-up was 7.2 years (interquartile range: 4.2-10.9). In half the progressions, no previous recurrence was observed. No association between the number of recurrences and the risk of progression was detected. Even after 5 years free of event, patients had a 15% risk of recurrence. History of two or more recurrences increased by 4.5 the risk of subsequent recurrence. Time between two recurrences inferior to six months and multifocal localization increased the risk of recurrence., Conclusion: Surveillance of patients with TaG1 should be continued beyond 5 years of follow-up. However, cystoscopy exams could be spaced after 5 years. Multiple TaG1 recurrences did not appear to be prognostic for disease progression, but increased significantly the risk of subsequent recurrences. Short time between two recurrences and multifocal localization may serve to adapt monitoring of patients with TaG1 Bladder cancer., Competing Interests: The authors have declared that no competing interests exist.

Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high. Improvements to patient selection and identification of at-risk patients are central to reducing mortality. We aimed to determine if cancer aggressiveness correlates with androgen levels in patients undergoing radical prostatectomy for localized PCa. We performed a prospective, multicenter cohort study between June 2013 and June 2016, involving men with localized PCa scheduled to undergo radical prostatectomy. Clinical and hormonal patient data (testosterone deficiency, defined by total testosterone (TT) levels < 300 ng/dL and/or bioavailable testosterone (BT) levels < 80 ng/dL) were prospectively collected, along with pathological assessment of preoperative biopsy and subsequent radical prostatectomy specimens, using predominant Gleason pattern (prdGP) 3/4 grading. Of 1343 patients analyzed, 912 (68%) had prdGP3 PCa and 431 (32%) had high-grade (prdGP4, i.e., ISUP ≥ 3) disease on prostatectomy specimens. Only moderate concordance in prdGP scores between prostate biopsies and prostatectomy specimens was found. Compared with patients with prdGP3 tumors (i.e., ISUP ≤ 2), significantly more patients with prdGP4 cancers had demonstrable hypogonadism, characterized either by BT levels (17.4% vs. 10.7%, p < 0.001) or TT levels (14.2% vs. 9.7%, p = 0.020). BT levels were also lower in patients with prdGP4 tumors compared to those with prdGP3 disease. Testosterone deficiency (defined by TT and/or BT levels) was independently associated with higher PCa aggressiveness. BT is a predictive factor for prdGP4 disease, and evaluating both TT and BT to define hypogonadism is valuable in preoperative assessment of PCa (AndroCan Trial: NCT02235142).

Von Hippel-Lindau (VHL) disease is a rare autosomal dominant syndrome that is the main cause of inherited clear-cell renal cell carcinoma (ccRCC), which generally occurs in the form of multiple recurrent synchronized tumors. Affected patients are carriers of a germline mutation in the VHL tumor suppressor gene. Somatic mutations of this gene are also found in sporadic ccRCC and numerous pan-genomic studies have reported a dysregulation of microRNA (miRNA) expression in these sporadic tumors. In order to investigate the molecular mechanisms underlying the pathogenesis of VHL-associated ccRCC, particularly in the context of multiple tumors, the present study characterized the mRNA and miRNA transcriptome through an integrative analysis compared with sporadic renal tumors. In the present study, two series of ccRCC samples were used. The first set consisted of several samples from different tumors occurring in the same patient, for two independent patients affected with VHL disease. The second set consisted of 12 VHL-associated tumors and 22 sporadic ccRCC tumors compared with a pool of normal renal tissue. For each sample series, an expression analysis of miRNAs and mRNAs was conducted using microarrays. The results indicated that multiple tumors within the kidney of a patient with VHL disease featured a similar pattern of miRNA and gene expression. In addition, the expression levels of miRNA were able to distinguish VHL-associated tumors from sporadic ccRCC, and it was identified that 103 miRNAs and 2,474 genes were differentially expressed in the ccRCC series compared with in normal renal tissue. The majority of dysregulated genes were implicated in 'immunity' and 'metabolism' pathways. Taken together, these results allow a better understanding of the occurrence of ccRCC in patients with VHL disease, by providing insights into dysregulated miRNA and mRNA. In the set of patients with VHL disease, there were few differences in miRNA and mRNA expression, thus indicating a similar molecular evolution of these synchronous tumors and suggesting that the same molecular mechanisms underlie the pathogenesis of these hereditary tumors.

Introduction: The influence of the delay between prostate biopsy and radical prostatectomy for patients with localized prostate cancer is controversial. The objective of this study was to establish a time limit between prostate biopsy and radical prostatectomy beyond which the risks of upgradging and biochemical recurrence (BCR) are increased., Material and Methods: Between January 2013 and January 2017, a retrospective analysis of the clinical, biological and histological data of 513 patients treated with radical prostatectomy for localized prostate cancer was performed in a single center. The primary endpoint was the assessment of the risk of BCR by the difference between post-biopsy USCF-CAPRA and post-surgical CAPRA-S scores. The secondary endpoint was the evaluation of the upgrading by the difference between the Gleason score on biopsy and on surgical specimen. The risks of BCR and upgrading were compared by Student test according to different delays between prostate biopsy and radical prostatectomy. The shortest delays for which a significant difference was found were reported., Results: In this study, 513 patients were included. The median age at the time of the biopsy was 65 years (IQR: 60-69). The median preoperative PSA was 7.30ng/mL (IQR: 5.60-9.94). The median time between biopsy and surgery was 108 days (IQR: 86-141). For the entire cohort, the risk of BCR was significantly higher above a threshold of 90 days (P=0.039). No threshold was found for Gleason 6(3+3) patients. A 90-day threshold was found for Gleason 7(3+4) patients (P=0.038). Gleason patients≥8 had more upgrading beyond a 60-day threshold (P=0.040)., Conclusion: Our study showed that after a 3 months delay, the risk of BCR was significantly higher for localized prostate cancer. It seemed possible to extend this period for low-risk patients, whereas it seemed necessary to keep it for intermediate-risks and to reduce it to 2 months for high-risks., Level of Evidence: 4., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: We aim to correlate multiparametric magnetic resonance imaging (mpMRI) of the prostate reporting (Prostate Imaging Reporting and Data System [PI-RADS] version 2) with the Gleason score into both radical prostatectomy (RP) specimen and MRI fusion-targeted biopsies (FTB)., Methods: mpMRI of 74 patients who underwent an RP after FTB were retrospectively reviewed. The Gleason score distribution was compared according to the PI-RADS score using the Kruskal-Wallis test. Results were compared to those of the mpMRI-guided biopsy of the same anatomical zone. For comparison, 903 RP specimen and their corresponding classical biopsies were also reviewed. Cohen's kappa concordance test was used to compare biopsies and prostatectomy specimen analyses., Results: An exact match between Gleason grade in RP specimen and FTB was found in 62% of the cases. There was no significant difference in Gleason score ≤7 (3 + 4) vs. ≥7 (4 + 3) distribution according to the PI-RADS scores (p = 0.096). Overall, Kappa coefficients were similar with MRI-targeted biopsies compared to classical biopsies (κ = 0.378, 95% CI [0.194-0.563], and κ = 0.316, 95% CI [0.259-0.374], respectively)., Conclusions: PI-RADS score was not associated with significant differences regarding Gleason score distribution within target. Moreover, concordance of Gleason score in both MRI-targeted and classical biopsies with those within target in RP specimen was weak., (© 2017 S. Karger AG, Basel.)

Objective: To provide an epidemiologic description of Kikuchi-Fujimoto disease (KFD), and to describe its relationship with systemic lupus erythematosus (SLE) in a population of sub-Saharan origin., Methods: Patients were retrospectively included on the basis of lymph node histology compatible with KFD reported in Martinique from 1991 until 2013. In order to describe the characteristics of the disease in a larger cohort, we subsequently included more patients of Afro-Caribbean origin from Guadeloupe and French Guiana., Results: In Martinique, mean annual incidence between 1991 and 2013 was 2.78 cases for 1 million inhabitants (95% confidence interval 1.73-3.93). A total of 36 Afro-Caribbean patients from the 3 French American regions were included. Mean age was 30.5 years (range 5-59 years) and the female:male ratio was 3:1. The main characteristics were cervical adenopathies (88.8%), fever (83.3%), asthenia (73.0%), weight loss (64.4%), and recurrence in 33.3%. KFD was associated with lupus (n = 9 for SLE, n = 2 for cutaneous lupus) in 36.6% (11 of 30)., Conclusion: We report the first epidemiologic description of KFD in a population of sub-Saharan origin. According to our data, this disease is present in the black African diaspora and is strongly associated with autoimmune diseases, particularly lupus., (© 2016, American College of Rheumatology.)

Background and Purpose: Carotid bulb diaphragm (CBD) has been described in young carotid ischemic stroke (CIS) patients, especially in blacks. However, the prevalence of CBD in CIS patients is unknown, and whether CBD is a risk factor for CIS remains unclear. We assessed the association between CBD and incident CIS in a population-based study., Methods: We selected all young (<55 years) CIS patients from a 1-year population-based cohort study in the Afro-Caribbean population of Martinique in 2012. All patients had a comprehensive work-up including a computed tomographic angiography. We calculated CIS associated with ipsilateral CBD incidence with 95% confidence intervals using Poisson distribution. We then selected age- and sex-matched controls among young (<55 years) Afro-Caribbean stroke-free patients admitted for a road crash who routinely had computed tomographic angiography. Odds ratio (ORs) were calculated by conditional logistic regression adjusted for hypertension, dyslipidemia, diabetes and smoking., Results: CIS associated with ipsilateral CBD incidence was 3.8 per 100 000 person-years (95% confidence interval, 1.4-6.1). Prevalence of ipsilateral CBD was 23% in all CIS and 37% in undetermined CIS patients. When restricted to undetermined CIS, CBD prevalence was 24 times higher than that in controls (adjusted OR, 24.1; 95% confidence interval, 1.8-325.6)., Conclusions: CBD is associated with an increased risk of ipsilateral CIS in young Afro-Caribbean population., (© 2016 American Heart Association, Inc.)

Introduction: Lung cancer is the leading cause of cancer deaths in the United States and worldwide. Biomarker testing is critical to personalized therapy in lung adenocarcinoma and has been extensively investigated in whites and Asians. However, little information addresses the underlying genetic changes among Caribbean and African Caribbean patients. In this study, we identified targetable biomarkers in Caribbean patients with lung adenocarcinoma., Methods: DNA extracted from lung adenocarcinoma specimens collected from 157 patients in whom primary lung adenocarcinoma was diagnosed from 2013 to 2015 in the University Hospital of Martinique was tested for mutation of the epidermal growth factor receptor gene (EGFR), Kirsten rat sarcoma viral oncogene homolog gene (KRAS), B-Raf proto-oncogene, serine/threonine kinase gene (BRAF), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS), and MMNG HOS Transforming gene (MET). Clinical characteristics of our patients have been retrospectively gathered and correlated with mutational status., Results: Mutations in EGFR were identified in 57 cases (36%). Women accounted for 68% of patients with mutations versus 38% of those without mutations (p < 0.001). Eighteen percent of patients with mutations were smokers versus 62% of patients without mutations (p < 0.001). Sex, smoking habit, and age were significantly associated with differences in mutational status in univariate analysis, and the difference remained statistically significant in multivariate analysis (p = 0.0411, p = 0.001, and p = 0.0483, respectively). After the analysis was restricted to patients born in the French West Indies, the mutation rates reached 41%., Conclusion: Patients in Martinique, and specifically those of African descent, show very high levels of EGFR mutation as opposed to what can be found in mainland France or in African Americans. These findings may be ascribed to low tobacco consumption as well as to genetic factors. Systematic screening in patients of African Caribbean origin should be prescribed., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

To systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer, we searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects. The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system. A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review. We attributed a level of evidence (LoE) of IA to PSA for early PCa detection, but we do not recommend its use in mass screening. Emerging biomarkers were assessed in prospective case-control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA (n=5); fusion oncogenes (n=2). These studies used biopsy results for prostate cancer to determine specificity and sensitivity, but they did not assess the effect on PCa mortality. The LoE attributed was III-C. PSA can be used for early prostate cancer detection but mass screening is not recommended. Studies on other biomarkers suggest that they could be used, individually or in combination, to improve the selection of patients with elevated PSA levels for biopsy, but RCTs assessing their impact on prostate cancer management and mortality are needed. A better use of available tests is possible for men at risk in order to maximize the risk-benefit ratio.

Background: To compare histological feature of prostate cancer (PCa) according androgenic status in patients who underwent radical prostatectomy (RP)., Methods: Between March 2007 and September 2013, we prospectively analysed 937 patients who were referred to our centre for RP. Clinical, pathological and biological data have been prospectively collected. Preoperative total testosterone (TT) and bioavailable testosterone (BT) serum determinations were carried out. The threshold for low serum testosterone was set at TT<3 ng/ml. Preoperative PSA value was registered. Gleason score (GS) and predominant Gleason pattern were determined in prostate biopsies and in prostate tissue specimens, crosschecked by two uro-pathologists., Results: Nine hundred and thirty-seven consecutive patients were included. In all, 14.9% patients had low TT in the population. An exact match between biopsy and prostate specimens in GS grading was observed for 50.6% patients (n=474). Also, 40.9% of all patients were upgraded (n=383): 45.3% (n=63) in low serum testosterone patients and 40.1% (n=320) in normal serum testosterone patients. For prostate specimens, the proportion of patients with predominant Gleason pattern 4 was higher in patients with low TT compared with normal TT (41.7% vs 29.1%, P=0.0029). In all, 20.1% were upgraded from predominant Gleason pattern 3 on biopsies specimen to predominant Gleason 4 pattern on the prostate specimen in patients with low TT, whereas 11.6% were upgraded for normal TT patients (P=0.002)., Conclusions: Low serum testosterone is an independent risk factor for predominant Gleason pattern 4 on prostate specimen after RP and for upgrading from low- to high-grade cancer between prostate needle biopsies and RP specimen. This observation should be taken into account in localised PCa management, especially for active surveillance or when a nerve-sparing approach is considered.

Purpose: Positive surgical margins (PSMs) after radical prostatectomy (RP) are a known factor associated with biochemical recurrence (BCR) and raise the issue of adjuvant treatment by radiotherapy versus salvage treatment at recurrence. To help this choice, our study aimed to analyze BCR-free survival and factors associated with BCR in patients with PSM and undetectable postoperative prostate-specific antigen (PSA)., Methods: Between 2005 and 2008, 630 patients had RP for localized prostate cancer in our center. We included patients with PSM, uninvaded nods, undetectable postoperative PSA and no adjuvant treatment. The 5-year BCR-free survival was calculated using Kaplan-Meier method. Logistic regression models were used to determine the factors associated with BCR in univariate and multivariate analyses (Cox model)., Results: The PSM rate was 32.7 % (n = 206 patients), and 110 patients corresponded to the inclusion criteria. The median follow-up was 72 months. The BCR rate was 30 % with a 5-year BCR-free survival of 83.9 %. The factors significantly associated with BCR were preoperative PSA, predominance and percentage of Gleason 4, tumor volume, PSM length and predominance of Gleason 4 at the margin. In the multivariate analysis, the remaining two significant factors were PSM length [OR 4.35, 95 % CI (1.011-1.421), p = 0.037] and tumor volume [OR 4.29, 95 % CI (1.011-1.483), p = 0.038]., Conclusion: Over a 5-year follow-up, only one-third of patients experienced BCR. It might be reasonable to postpone adjuvant radiotherapy for patients with PSM and undetectable PSA after RP. Tumor volume and PSM length were associated with BCR and should be taken into account in the postoperative treatment management.

Objectives: Handling and pathologic analysis of radical prostatectomy specimens are crucial to confirm the diagnosis of prostate cancer and evaluate prognostic criteria., Material and Methods: A systematic review of the scientific literature was performed in the Medline database (PubMed), using different associations of the following keywords: prostate cancer; prostatectomy; specimen; handling; pathology; tumor staging; Gleason score; surgical margin; prognosis; frozen section; lymph node; biomarkers. A particular search was done on specimen management and characterization of tissue prognostic factors., Results: Handling of both radical prostatectomy specimen and lymph node dissection is standardized according to international criteria. Although the main histoprognostic factors are still Gleason score, pathologic staging and margin status, these criteria have been refined these last 10 years, allowing to improve the prediction of relapse after surgical treatment., Conclusion: The standardization of handling and pathology reporting of radical prostatectomy specimens will be mandatory for treatment uniformization according to risk stratification in prostate cancer and personalization of therapeutic approaches., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Introduction: Chondroid syringoma (CS) is a rare cutaneous tumor characterized by mixte epithelial and mesenchymal component. The confident histological diagnosis can be obtained by immuno-histochemistry study. Here we present 10 new cases with their clinico-hystological characteristics., Methods: The 10 cases were observed between January 2000 and august 2013, in Fort-de-France and Louis-Mourier universitary hospitals. For all the cases a controlled histological study was performed by a dermatopathologist expert and immuno-histochemistry was added. Clinical and immuno-histological data were analyzed., Results: The lesions were almost localized on the face (3/10) and the extremities (3/10). The size was about 1.2 to 5.2cm. Every case was treated by surgery, no malignant case was diagnosed. Histologically, all the 10 cases presented as a well-limited dermic tumor with a mixte epithelial and mesenchymal component. The stroma was myxo-chondroid, and the epithelial component consisted in epithelial cavities lined by one or two cell layers with eccrine (4/10) or apocrine (5/10) features. Immuno-chemistry study reveals positivity for EMA, ACE and CK7 for the internal cells, and positivity for S100 protein and vimentin of the extern cell layer., Discussion: Chondroid syringoma is characterized by a mixte epithelial with eccrine and apocrine cells and a myxo-chondroid stroma. Our study has some clinical and histological particularities (lesions on the extremities, epidermic connecting…). The main differentials diagnoses are the other annexial tumors. The treatment is surgical., Conclusion: The histological diagnosis of CS is quite easy, but in case of doubt, immuno-chemistry will help, showing a double mesenchymal and epithelial differentiation., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Purpose: Selecting patients with metastatic clear-cell renal cell carcinoma (m-ccRCC) who might benefit from treatment with targeted tyrosine kinase inhibitors (TKI) is a challenge. Our aim was to identify molecular markers associated with outcome in patients with m-ccRCC treated with sunitinib., Experimental Design: We performed global transcriptome analyses on 53 primary resected ccRCC tumors from patients who developed metastatic disease and were treated with first-line sunitinib. We also determined chromosome copy-number aberrations, methylation status, and gene mutations in von Hippel-Lindau and PBRM1. Molecular data were analyzed in relation with response rate (RR), progression-free survival (PFS), and overall survival (OS). Validation was performed in 47 additional ccRCC samples treated in first-line metastatic setting with sunitinib., Results: Unsupervised transcriptome analysis identified 4 robust ccRCC subtypes (ccrcc1 to 4) related to previous molecular classifications that were associated with different responses to sunitinib treatment. ccrcc1/ccrcc4 tumors had a lower RR (P = 0.005) and a shorter PFS and OS than ccrcc2/ccrcc3 tumors (P = 0.001 and 0.0003, respectively). These subtypes were the only significant covariate in the multivariate Cox model for PFS and OS (P = 0.017 and 0.006, respectively). ccrcc1/ccrcc4 tumors were characterized by a stem-cell polycomb signature and CpG hypermethylation, whereas ccrcc3 tumors, sensitive to sunitinib, did not exhibit cellular response to hypoxia. Moreover, ccrcc4 tumors exhibited sarcomatoid differentiation with a strong inflammatory, Th1-oriented but suppressive immune microenvironment, with high expression of PDCD1 (PD-1) and its ligands., Conclusions: ccRCC molecular subtypes are predictive of sunitinib response in metastatic patients, and could be used for personalized mRCC treatment with TKIs, demethylating or immunomodulatory drugs., (©2015 American Association for Cancer Research.)

Purpose: To identify the MRI sequences producing the greatest pancreatic adenocarcinoma conspicuity and to assess correlations linking MRI signal intensity and apparent diffusion coefficient to histopathological findings., Methods: We retrospectively included 22 patients with pancreatic adenocarcinoma who underwent MRI (1.5 or 3 T) before surgical resection. Fat-suppressed (FS) T1- and T2-weighted sequences; 3D FS dynamic T1-weighted gadolinium-enhanced gradient-echo (GRE) imaging at the arterial, portal, and delayed phases; and diffusion-weighted imaging (DWI) with b values of 600-800 s/mm(2) were reviewed. On each sequence, we assessed tumor conspicuity both qualitatively (3-point scale) and quantitatively (tumor-to-proximal and -distal pancreas contrast ratios), and we performed paired Wilcoxon tests to compare these data across sequences. We evaluated correlations between histopathological characteristics and MRI features., Results: 21/22 (95%) tumors were hypointense by 3D FS T1 GRE arterial phase imaging, which produced the greatest tumor conspicuity (p ≤ 0.02). By DWI, 5/20 (25%) of tumors were isointense. The correlation between size by histology and MRI was strongest with DWI. A progressive enhancement pattern was associated with extensive and dense fibrous stroma (p ≤ 0.03)., Conclusions: 3D FS T1 GRE arterial phase imaging produces greater pancreatic adenocarcinoma conspicuity compared to DWI but underestimates tumor size. DWI provides the best size evaluation but fails to delineate the tumor in one-fourth of cases.

Purpose: MITF/TFE translocation renal cell carcinoma (TRCC) is a rare subtype of kidney cancer. Its incidence and the genome-wide characterization of its genetic origin have not been fully elucidated., Experimental Design: We performed RNA and exome sequencing on an exploratory set of TRCC (n = 7), and validated our findings using The Cancer Genome Atlas (TCGA) clear-cell RCC (ccRCC) dataset (n = 460)., Results: Using the TCGA dataset, we identified seven TRCC (1.5%) cases and determined their genomic profile. We discovered three novel partners of MITF/TFE (LUC7L3, KHSRP, and KHDRBS2) that are involved in RNA splicing. TRCC displayed a unique gene expression signature as compared with other RCC types, and showed activation of MITF, the transforming growth factor β1 and the PI3K complex targets. Genes differentially spliced between TRCC and other RCC types were enriched for MITF and ID2 targets. Exome sequencing of TRCC revealed a distinct mutational spectrum as compared with ccRCC, with frequent mutations in chromatin-remodeling genes (six of eight cases, three of which were from the TCGA). In two cases, we identified mutations in INO80D, an ATP-dependent chromatin-remodeling gene, previously shown to control the amplitude of the S phase. Knockdown of INO80D decreased cell proliferation in a novel cell line bearing LUC7L3-TFE3 translocation., Conclusions: This genome-wide study defines the incidence of TRCC within a ccRCC-directed project and expands the genomic spectrum of TRCC by identifying novel MITF/TFE partners involved in RNA splicing and frequent mutations in chromatin-remodeling genes., (©2014 American Association for Cancer Research.)

Muscle-invasive bladder carcinoma (MIBC) constitutes a heterogeneous group of tumors with a poor outcome. Molecular stratification of MIBC may identify clinically relevant tumor subgroups and help to provide effective targeted therapies. From seven series of large-scale transcriptomic data (383 tumors), we identified an MIBC subgroup accounting for 23.5% of MIBC, associated with shorter survival and displaying a basal-like phenotype, as shown by the expression of epithelial basal cell markers. Basal-like tumors presented an activation of the epidermal growth factor receptor (EGFR) pathway linked to frequent EGFR gains and activation of an EGFR autocrine loop. We used a 40-gene expression classifier derived from human tumors to identify human bladder cancer cell lines and a chemically induced mouse model of bladder cancer corresponding to human basal-like bladder cancer. We showed, in both models, that tumor cells were sensitive to anti-EGFR therapy. Our findings provide preclinical proof of concept that anti-EGFR therapy can be used to target a subset of particularly aggressive MIBC tumors expressing basal cell markers and provide diagnostic tools for identifying these tumors., (Copyright © 2014, American Association for the Advancement of Science.)

We report here the clinical case of an Afro-Caribbean patient referred for complete atrioventricular block for whom a diagnosis of hereditary cardiac amyloidosis was eventually confirmed. Hereditary cardiac amyloidosis is an emerging threat in the Caribbean, and the main goal of this report is to raise the awareness of the disease among physicians.

Background: There are no validated markers that predict outcome in metastatic renal cell cancer (mRCC) patients treated with sunitinib. Recently, single nucleotide polymorphism (SNP) rs9582036 in VEGFR1 has been proposed as a predictor of progression-free survival (PFS) and overall survival (OS) to bevacizumab in patients with pancreatic cancer and rs7993418 in VEGFR1 as predictor for PFS in mRCC-patients treated with bevacizumab. Here, we aim to study the impact of these SNPs in mRCC patients treated with sunitinib., Methods: We included patients with mRCC treated in 15 institutions in France and Belgium. Patients received sunitinib as first-line targeted therapy. We assessed response, time-to-tumor progression (TTP), OS, and clinical and biochemical parameters associated with outcome. We genotyped rs9582036 and rs7993418 as well as three other surrounding SNPs in VEGFR1: rs9554320, rs9554316 and rs9513070. Association between SNPs and treatment outcome were studied by univariate analysis and by multivariate Cox regression using relevant clinical factors associated with TTP and OS as covariates., Findings: Ninety-one patients were included. We found that mRCC patients with the CC-variant in rs9582036 in VEGFR1 have a poorer response rate (RR) (0% vs. 46%, p = 0.028), a poorer PFS (10 vs. 18 months, p = 0.033 on univariate and 0.06 on multivariate analysis) and a poorer OS (14 vs. 31 months, p = 0.019 on univariate and 0.008 on multivariate analysis) compared to patients with the AC- and AA-genotypes. mRCC patients with the AA-variant in rs9554320 in VEGFR1 have a poorer PFS (12 vs. 21 months, p = 0.0066 on univariate and 0.005 on multivariate analysis) and a poorer OS (22 vs. 34 months, p = 0.019 on univariate and 0.067 on multivariate analysis) compared to patients with the AC- and CC-genotypes. Interpretation. mRCC patients with the CC-genotype in VEGFR1 SNP rs9582036 have a poorer response rate, PFS and OS when treated with sunitinib. These findings are in agreement with the association of rs9582036 and outcome observed in bevacizumab treated pancreatic cancer patients. Prospective validation of this SNP is warranted.

Oncocytomas represent 3 to 7% of renal masses and behave as benign tumours. Nephron-sparing procedures are preferred for biopsy confirmed lesions; however, giant oncocytomas have been generally treated by radical nephrectomy. We report the first case of partial nephrectomy in a 45-year-old man who presented with a 20-cm oncocytoma. At the 1 year follow-up, he had a normal functioning kidney. Despite the difficulty of this procedure, partial nephrectomy for very large benign tumours can be considered in appropriately selected young patients.

Introduction: The sub Comittee prostate of the CCAFU established guidelines for diagnostic, treatment, evaluation and standart of care of prostate cancer., Methods: Guidelines 2010 were updated based on systematic literature search performed by the sub-Comittee in Medline and PubMed databases to evaluate references, levels of evidence and grade of recommandation., Results: Pathological examination of the tissue specimens was defined specifically for Gleason score according to ISP 2005 recommandations. Prostate and pelvis RMN became the reference in terms of radiological exam. Individual and early diagnosis of prostate cancer was defined and role of PSA was precised. Active surveillance became one of the standart of care of low-risk tumors, radical prostatectomy remained one of the options for all risk group tumors, length of hormonotherapy in association with radiotherapy was precised according to the risk group. Side effects of hormonotherapy treament needed specific supervision ; hormonotherapy had no indication in case of non metastatic tumors and intermittent hormonotherapy in metastatic tumors. New hormonal drugs in pre and post chemotherapy and bone target drugs opened new therapeutics pathways., Conclusion: From 2010 to 2013, standarts of care of prostate cancer were modified because of results of prospective studies and new therapeutics. They allowed precise treatments for each specific clinical situation. In the future, multidisciplinary treatments for high risk tumors, time of adjuvant treatment and sequencies of new hormonal treatment had to be defined., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Purpose: Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer involving the TFEB/TFE3 genes. We aimed to investigate the genomic and epigenetic features of this entity., Experimental Design: Cytogenomic analysis was conducted with 250K single-nucleotide polymorphism microarrays on 16 tumor specimens and four cell lines. LINE-1 methylation, a surrogate marker of DNA methylation, was conducted on 27 cases using pyrosequencing., Results: tRCC showed cytogenomic heterogeneity, with 31.2% and 18.7% of cases presenting similarities with clear-cell and papillary RCC profiles, respectively. The most common alteration was a 17q gain in seven tumors (44%), followed by a 9p loss in six cases (37%). Less frequent were losses of 3p and 17p in five cases (31%) each. Patients with 17q gain were older (P=0.0006), displayed more genetic alterations (P<0.003), and had a worse outcome (P=0.002) than patients without it. Analysis comparing gene-expression profiling of a subset of tumors bearing 17q gain and those without suggest large-scale dosage effects and TP53 haploinsufficiency without any somatic TP53 mutation identified. Cell line-based cytogenetic studies revealed that 17q gain can be related to isochromosome 17 and/or to multiple translocations occurring around 17q breakpoints. Finally, LINE-1 methylation was lower in tRCC tumors from adults compared with tumors from young patients (71.1% vs. 76.7%; P=0.02)., Conclusions: Our results reveal genomic heterogeneity of tRCC with similarities to other renal tumor subtypes and raise important questions about the role of TFEB/TFE3 translocations and other chromosomal imbalances in tRCC biology., (©2013 AACR.)

Unlabelled: What's known on the subject? and what does the study add?: Local relapse of renal cell carcinoma following radical nephrectomy is rare, and surgical removal provides the only opportunity for cure. Open surgery has been established as the usual approach for these tumours. It is, however, associated with significant morbidity. Our study describes the largest series of laparoscopic treatment of local relapse of renal cell carcinoma with the longest follow-up. We show that the laparoscopic approach is feasible in expert centres. It provides faster recovery and fewer complications with satisfactory oncological outcomes in selected patients., Objective: To assess the feasibility and oncological outcomes of laparoscopic treatment for local relapse of renal cell carcinoma., Patients and Methods: Nine patients were treated by a pure laparoscopic approach for local recurrence of a renal tumour between 2005 and 2011 by a single surgeon (HB), following an initial open radical nephrectomy for the primary tumour. Clinical and histopathological data were collected prospectively and analysed retrospectively. Seven patients were treated by a transperitoneal approach and two patients had a retroperitoneal approach., Results: Relapse occurred within a mean time of 83 months (7-168) following nephrectomy. Recurrent tumour size varied from 2.5 to 4.5 cm. All surgeries were performed laparoscopically without need for conversion. Mean operative duration was 144 min (40-240), mean estimated blood loss was 430 mL (50-1300) and mean hospital stay was 4.5 days (3-6). Three patients had Clavien grade I intraoperative complications. Late complications were noted in two patients (Clavien I and IIIb). Pathology confirmed clear cell carcinoma in all patients with an absence of sarcomatoid features and negative surgical margins. Three patients had neoadjuvant treatment and two patients had adjuvant treatment. In all, 67% of patients were disease free with a mean follow-up period of 3 years., Conclusions: Surgical removal of isolated local recurrence remains the only possibility of cure in patients with renal cell carcinoma. We demonstrated that the laparoscopic approach is a safe and feasible alternative treatment option for selected cases with low morbidity and satisfactory oncological outcomes., (© 2013 BJU International.)

Anal intraepithelial lesions are caused by chronic infection with oncogenic types of human papillomavirus. Their incidence and prevalence are increasing, especially among patients with HIV infection. Their natural history is not well known, but high-grade intraepithelial lesions seem to have an important risk to progress to squamous cell carcinoma. Their treatment can be achieved by many ways (surgery, coagulation, imiquimod, etc.) but there is a high rate of recurrent lesions. Pretherapeutic evaluation should benefit from high-resolution anoscopy. Periodic physical examination and anal cytology may probably be interesting for screening the disease among patients with risk factors. Vaccine against oncogenic types of papillomavirus may prevent the development of anal intraepithelial neoplasia., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

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. Twelve tumours that could not be classified as RO or CHRC were considered as HOCT. Hale staining and cytokeratin 7 (CK7) immunostaining were performed. Genomic profile was established by array comparative genomic hybridisation (array-CGH) on frozen samples. Mean age at diagnosis was 70 years (range 46-83). No recurrence was observed (median follow-up: 18 months; range 9-72). Tumour size ranged from 1 to 11 cm. HOCT showed an admixture of RO- and ChRCC-like areas and/or "hybrid" cells with overlapping cytonuclear and/or histochemical features. Hale staining was apical in 50 to 100 % of cells, and CK7 was expressed in 10 to 100 % of cells. Genomic profile was balanced in seven cases or showed a limited number of random imbalances in five cases, as observed in RO. In no instances were observed the characteristic chromosome losses of ChRCC. These results suggest that so called HOCT are not true hybrid tumours and rather could represent a morphological variant of RO. From a diagnostic perspective, an array-CGH analysis could be performed in ambiguous ChRCC/RO cases to formally exclude the diagnosis of ChRCC.

Deep gastrointestinal involvement in endometriosis is characterised by fibrous, retractile thickening of the intestinal wall. The most common location is the upper rectum, in contiguity with a lesion of the torus uterinus. As part of a preoperative assessment, it is essential to establish an accurate and exhaustive map of intestinal lesions so that the surgeon can plan his actions. Transvaginal sonography and MRI correctly analyse pelvic and rectal involvement. Given the frequency of multiple intestinal sites, particularly sigmoid and associated ileo-caecal lesions, water enema CT should be performed. The role of rectal endoscopic sonography is debated., (Copyright © 2012 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Extemporaneous examination of a thoracopulmonary lesion has an unquestionable interest when pre-surgical diagnostic workup has not allowed determining its exact nature. This examination, the sole objective of which is to guide the surgical approach, is especially important in lung pathology, due to the limited non-surgical access to thoracic lesions and the morbidity and mortality of repeated surgery. Its yield as a decision-making procedure is of utmost importance in many clinical situations, and a close collaboration between thoracic surgeons and pathologists is required to ensure its quality, in a context of mutual confidence that requires time and experience. After a presentation of the indications and practical modalities of extemporaneous examination, we will underline its limitations and insist on difficult situations for the pathologist and inadequate indications., (Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Adenosine and inosine are both key intracellular energy substrates for nucleotide synthesis by salvage pathways, especially during ischemic stress conditions. Additionally they both possess cell protective and cell repair properties. The objective of this study is to detect potential advantages of the combination of adenosine and inosine versus each drug alone, in terms of ventricular function, infarct size reduction and angiogenesis. Myocardial ischemia was created in rodents and treated with adenosine, inosine or their combination. Results of experiments showed that the combination of both drugs significantly reduced infarct size and improved myocardial angiogenesis and ventricular function. The two compounds, while chemically similar, use different intracellular pathways, allowing for complementary biological activities without overlapping. The drug combination at specific 1 : 5 adenosine : inosine dose ratio demonstrated positive cardiologic effects, deserving further evaluation as an adjunct to reperfusion techniques during and after acute coronary syndrome. The association of adenosine and inosine may contribute to reduce myocardial infarction morbidity and mortality rates.

So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.

Fumarate hydratase (FH) mutation causes hereditary type 2 papillary renal cell carcinoma (PRCC2). The main effect of FH mutation is fumarate accumulation. The current paradigm posits that the main consequence of fumarate accumulation is HIF-α stabilization. Paradoxically, FH mutation differs from other HIF-α stabilizing mutations, such as VHL and SDH mutations, in its associated tumor types. We identified that fumarate can directly up-regulate antioxidant response element (ARE)-controlled genes. We demonstrated that aldo-keto reductase family 1 member B10 (AKR1B10) is an ARE-controlled gene and is up-regulated upon FH knockdown as well as in FH null cell lines. AKR1B10 overexpression is also a prominent feature in both hereditary and sporadic PRCC2. This phenotype better explains the similarities between hereditary and sporadic PRCC2., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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. Most tumours (58%) occurred in the absence of renal disease. Mean patient age was 58.1 years. Tumours were small (mean size: 2.4 cm) and classified as pT1. Histological characteristics consisted of tubules and papillae lined by a single layer of small clear cells harbouring low-grade nuclei (Fuhrman grades 1 or 2). Architectural variations, with compact areas (41% of cases) and a micro- or macrocystic pattern (67% of cases) were observed frequently. Immunostaining demonstrated diffuse, strong expression of cytokeratin 7 and vimentin, whereas CD10, racemase, RCC antigen, translocation factor E3, TFE3 and translocation factor EB were consistently negative. In seven tumours, array-CGH detected no chromosomal imbalances., Conclusions: Clear-cell papillary renal cell carcinoma (ccpRCC) were differentiated from other renal neoplasms by a specific constellation of histopathological and immunohistochemical features, without characteristic genomic imbalances. Clinical, histopathological and genomic data suggested that these tumours have a low potential for malignancy., (© 2011 Blackwell Publishing Limited.)

The urothelial carcinoma of the prostate is an entity which is necessary to recognize. The infiltration of the prostatic stroma is a major prognostic factor. The 2009 pTNM classification distinguish carcinoma in situ of the urethra with involvement of prostatic acini (pT2) from direct invasion of prostatic stroma through outside involvement (pT4). In case of non metastatic muscle invasive bladder cancer with major lymphatic invasion, the standard treatment remains neoadjuvant chemotherapy followed by radical cystectomy and extended lymphadenectomy. Only some patients can hope a complete response after neoadjuvant chemotherapy. For these responders, we can sometimes discuss, at an individual level, a bladder conservative strategy with an intensive surveillance., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Objective: In this report, we describe a new patient with unexplained familial bilateral pheochromocytoma. Following the recent description of TMEM127 as a new pheochromocytoma susceptibility gene, the aim of this study was to test the hypothesis of a causative TMEM127 gene mutation in this patient., Design: Pheochromocytoma susceptibility genes were analyzed in germline DNA and losses of heterozygosity (LOH) assessed by BAC array comparative genomic hybridization in tumor DNA. SDHB expression and S6 kinase (S6K) phosphorylation were analyzed by immunohistochemistry. Genome-wide expression microarray studies were performed, and vascular density was quantified after CD34 immunohistochemistry., Results: A first germline variant was identified in the SDHB gene (c.158G>A; p.Gly53Glu). However, a positive SDHB immunostaining in the tumor indicated that this SDHB variant was a non-functional polymorphism. A novel TMEM127 germline mutation (c.140C>A, p.Ala47Asp) associated with a 2q11 LOH was found. Transcriptome and immunohistochemical analyses showed that TMEM127-related pheochromocytoma clusterized with NF1-related and RET-related tumors in a large series of pheochromocytomas and paragangliomas, exhibited a reduced TMEM127 mRNA expression and displayed a low vascularization. The phosphorylation of S6K observed in this tumor was suggestive of an activation of the MTOR pathway., Conclusions: Pathological and genomic data demonstrated that a TMEM127 gene mutation not previously described was causative of a new case of familial bilateral pheochromocytoma. This report highlights the importance of supplementary analyses on tumor tissue to provide an accurate pheochromocytoma/paraganglioma genetic testing result to affected patients.

Purpose: Translocation renal cell carcinomas represent a distinct clinicopathological entity. Studying the natural history, biological behavior and potential prognostic factors are crucially warranted., Materials and Methods: We selected 54 patients with renal cell carcinoma with positive nuclear transcription factor E3 and transcription factor EB expression from the Juvenile RCC Network. Recurrence-free survival and overall survival were assessed., Results: Median patient age was 24 years (range 1 to 64) and the male-to-female ratio was 1:1.4. At diagnosis 35 patients (65%) had local disease while 19 (35%) presented with distant metastases. The latter patients were older (median age 36 years) and predominantly male (male-to-female ratio 2) whereas the former group had a median age of 16 years and a male-to-female ratio of 1:2.5. Overall 36 patients underwent complete tumor resection and of these 8 had recurring cancer. On univariate analysis only lymph node involvement and American Joint Committee on Cancer stage were associated with poor recurrence-free survival. When stratified according to lymph node status age 25 years or older was found to predict relapse (p = 0.03). With a median followup of 19.2 months (range 1 to 58) 3-year overall survival was 14.3% in patients with distant metastasis and 70.6% in those without distant metastasis. Distant metastasis developed in the 2 patients with ASPSCR1-TFE3 fusion vs 1 of 11 with other fusion genes., Conclusions: Transcription factor E3 and transcription factor EB renal cell carcinoma display different clinical behavior according to gender and age. Lymph node involvement represents the only factor that predicts recurrence. ASPSCR1-TFE3 might be the most aggressive among the transcription factor E3 fusion genes., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)