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Chikungunya nephropathy is an uncommon etiology of acute kidney injury, associated with the mosquito-borne chikungunya arbovirus (CHIKV). The very limited number of pathologic reports to date have only involved postmortem analyses. We here report 5 cases of acute kidney injury for which kidney biopsies were performed in patients with confirmed acute CHIKV infection, during the recent outbreak of chikungunya disease in the French West Indies. The patients ranged from 42 to 76 years of age. All of the patients developed kidney injury, 3 of whom required short-term dialysis and underwent a kidney biopsy. Analysis of kidney biopsies revealed 2 main histopathologic patterns: acute interstitial nephritis with predominant lymphoid inflammation and acute tubular injury. Epithelioid granulomas were observed in 2 cases. There were no glomerular lesions, except in biopsies from 2 patients, including 1 with a previous known primary focal segmental glomerulosclerosis. CHIKV antigen immunofluorescence microscopy revealed staining in tubular cells. In all of the cases, the short-term outcome was favorable, with recovery of kidney function.

Resume Introduction L’epidemiologie du cancer de prostate (CaP) en Guyane francaise (GF) n’est pas bien documentee. Elle differe de celle relevee aux Antilles en raison d’une population plus jeune, moins exposee aux pesticides agricoles mais ayant une plus grande difficulte d’acces aux soins et a l’information medicale. Materiel Les taux d’incidence et de mortalite disponibles dans le registre des cancers du departement sont etudies et rapportes pour la periode 2010–2014. Les caracteristiques des 242 series de biopsies prostatiques realisees entre janvier 2017 et octobre 2019 a Kourou pour suspicion clinique et/ou biologique (PSA > 4 ng/mL) de CaP sont decrites. Resultats L’incidence du CaP en GF est de 94,4°/°°°° et la mortalite specifique de 16,9°/°°°°. Parmi les biopsies, 77,7 % (188/242) sont positives avec un PSA moyen de 72,6 ng/mL (1–4000) a un âge moyen de 66 ans (50–89), 34 % (64/188) avec un TR anormal, 12,3 % (23/188) avec un PSA > 50 ng/mL et 28,2 % (53/188) avec un score de Gleason ≥ 8. Conclusion Malgre une population jeune, une exposition moins forte qu’aux Antilles aux facteurs de risque environnementaux et un taux de metissage important, le diagnostic precoce du CaP en GF est encore un defi a relever. Les taux d’incidence et de mortalite observes suggerent a la fois une sous declaration des cas et une prise en charge trop tardive ce qui est confirme par les caracteristiques anatomopathologiques defavorables des cancers diagnostiques et par les taux eleves de PSA au moment du diagnostic. Niveau de preuve 3.

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

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.

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

Resume Introduction L’influence de l’allongement du delai entre les biopsies de prostate et le traitement par prostatectomie radicale pour les patients presentant un cancer de prostate localise est controverse. L’objectif de cette etude etait d’etablir un delai limite entre biopsies de prostate et prostatectomie radicale au-dela duquel les risques d’upgradging et de recidive biochimique seraient majores. Materiel et methode Entre janvier 2013 et janvier 2017, une analyse retrospective des donnees cliniques, biologiques et histologiques de 513 patients ayant eu une prostatectomie radicale pour cancer de prostate localise a ete effectuee dans un centre unique. Le critere de jugement principal etait l’evaluation du risque de recidive biochimique par la difference entre les scores post-biopsies USCF-CAPRA et post-chirurgical CAPRA-S. Le critere de jugement secondaire etait l’evaluation de l’upgrading par la difference entre le score de Gleason sur biopsies et sur piece operatoire. Les risques de recidive biochimique et d’upgrading ont ete compares par test de Student en fonction de differents delais entre biopsies prostatiques et prostatectomie radicale. Les delais les plus courts pour lesquels une difference significative etait retrouvee ont ete rapportes. Resultats Dans cette etude, 513 patients ont ete inclus. L’âge median au moment de la biopsie etait de 65 ans (IQR : 60–69). Le PSA median pre-operatoire etait de 7,30 ng/mL (IQR : 5,60–9,94). Le delai median entre les biopsies et la chirurgie etait de 108 jours (IQR : 86–141). Pour la cohorte entiere, le risque de recidive biochimique apres prostatectomie radicale etait significativement plus eleve au-dela d’un seuil de 90 jours (p = 0,039). Aucun seuil n’a ete retrouve pour les patients Gleason 6(3 + 3). Un seuil de 90 jours a ete retrouve pour les patients Gleason 7(3 + 4) (p = 0,038). Les patients Gleason ≥ 8 presentait plus d’upgrading au-dela d’un seuil de 60 jours (p = 0,040). Conclusion Notre etude a montre qu’au-dela d’un delai de 3 mois, le risque de recidive biochimique apres prostatectomie radicale etait significativement plus eleve pour les cancers de prostate localises. Ce delai semblait pouvoir etre allonge chez les patients a faible risque, alors qu’il paraissait devoir etre conserve pour les risques intermediaires, et reduit a 2 mois pour les risques eleves. Niveau de preuve 4.

Background: Lung cancer is the leading cause of cancer-related death worldwide. Shorter survival has been repeatedly reported for patients of African ancestry. Multivariate analysis demonstrated that this gap could be a consequence of socio-economic disparities instead of genetic specificities. However, those results were obtained in a pre-targeted therapies era and the effect of tyrosine kinase inhibitors targeting EGFR are not known in this population. Objective: In this French West Indies study, we report overall survival (OS) in a frequently mutated population treated for lung adenocarcinoma within an equal-access healthcare system. Patients and Methods: Clinical, demographic, survival, and treatment data have been retrospectively assessed for all patients diagnosed with lung adenocarcinoma in the islands of Martinique and Guadeloupe between 2013 and 2015. Results: Two hundred and forty-one patients (82% African-Caribbean) were included. EGFR mutations were detected in 37% of all tumor specimens and were associated with non-smoker status in multivariate analysis. Median OS was 16.2 months. For patients with advanced disease, median OS was 11.5 months, depending on EGFR mutation (23 vs. 8.3 months for non-mutated patients, p = 0.0012). There was no difference in survival according to ethnicity or island. In multivariate analysis, performance status (PS) and EGFR mutation were the only independent prognostic factors. Conclusions: Despite a higher frequency of EGFR mutations in African-Caribbean patients, ethnicity was not an independent factor of OS in lung adenocarcinoma. Lower initial PS in this mainly non-smoking African-Caribbean population may explain the absence of a difference in OS.[Figure not available: see fulltext.].

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.

Tubulocystic renal cell carcinoma is a rare tumor with an indolent behavior in the majority of cases. In contrast, tubulocystic renal cell carcinoma with poorly differentiated foci has a bad prognosis with an aggressive and metastatic behavior. We present the case of a patient diagnosed with tubulocystic renal cell carcinoma with poorly differentiated foci.

Objectifs Les patients originaires d’Afrique subsaharienne ont une incidence et une mortalite par cancer de prostate plus eleve que les hommes caucasiens. L’objectif de cette etude etait d’evaluer les resultats anatomopathologiques d’une cohorte afro-antillaise diagnostiquee d’un cancer de prostate sur biopsies de prostate, et de les comparer a une cohorte de France metropolitaine a majorite caucasienne. Methodes Une etude retrospective comparative bicentrique a ete realisee entre un centre Martiniquais et un centre Parisien entre 2008 et 2016. Les donnees cliniques, biologiques et pathologiques etaient recueillies au diagnostic. Les biopsies etaient realisees selon le schema standard de 12 prelevements systematises. Le critere de jugement principal etait la classification de la societe internationale de pathologie urologique (ISUP) pour le score de Gleason. Le critere de jugement secondaire etait le taux de detection du cancer de prostate par les biopsies. Toutes les biopsies ont ete relues par le meme anatomopathologiste. Une analyse multivariee a ete realisee par regression lineaire. Resultats Sur les 1880 patients ayant beneficie de biopsies de prostate dans la cohorte afro-caribeenne, 945 ont eu un diagnostic de cancer de la prostate (50,3 %), et 500 patients sur 945 dans la cohorte metropolitaine (33,8 %). Les patients afro-antillais etaient plus âges (moyenne : 68,5 ans vs 67,5 ans, p = 0,028), avaient un stade clinique plus eleve (13,2 % vs 5,2 % cT3-4, p Tableau 1 , Tableau 2 et Fig. 1 ). Conclusion Les patients afro-antillais ne presentaient pas de resultats anatomopathologiques plus defavorable au diagnostic que les patients metropolitains, apres analyse multivariee. Les patients afro-antillais atteints de cancer de prostate pourraient s’attendre au meme pronostic que les patients caucasiens, au meme stade de la maladie, dans des centres presentant des conditions equivalentes d’acces aux soins.

Resume Objectifs La prise en charge des pieces de prostatectomie totale et leur analyse histopathologique sont essentielles pour confirmer le diagnostic et evaluer l’histo-pronostic des cancers de la prostate. Materiel et methodes Une revue de la litterature a ete effectuee a partir de la base de donnees PubMed, en privilegiant les articles recents (5 ou 10 dernieres annees), a partir des mots cles suivants : prostate cancer ; prostatectomy ; specimen ; handling ; pathology ; tumor staging ; Gleason score ; surgical margin ; prognosis ; frozen section ; lymph node ; biomarkers. Une attention particuliere a ete portee sur la prise en charge des prelevements et la caracterisation des criteres histo-pronostiques. Resultats La prise en charge des pieces de prostatectomie totale et des produits de curage ganglionnaire est actuellement standardisee selon des criteres internationaux. L’evaluation des facteurs histo-pronostiques principaux, que sont le score de Gleason, le stade pathologique et le statut des limites d’exerese, a beaucoup evoluee ces dernieres annees permettant une prediction accrue du risque de recidive apres traitement chirurgical. Conclusion La standardisation de la prise en charge et du compte rendu anatomopathologique de la prostatectomie totale represente un prealable a l’uniformisation des approches therapeutiques. Cette standardisation a un role crucial dans la stratification des malades atteints d’un cancer de la prostate et la personnalisation du traitement.

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). 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). 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]. 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.

Objective In accordance with the European Association of Urology guidelines, a second transurethral resection of the bladder (TURB) is recommended for high-grade or T1-category tumors. This practice brings into question the benefit of photodynamic diagnosis (PDD) in reducing the residual disease after TURB in patients with positive results on urine cytology showing high-grade cancer cells. Methods and materials A prospective, bicentric, randomized study comparing white light cystoscopy (WLC)+PDD with hexaminolevulinate arm with WLC alone (control arm) during the first TURB in patients with primary non–muscle-invasive bladder cancer and with positive results on urine cytology showing high-grade cancer cells. Patients underwent a first TURB with WLC and PDD or WLC alone, and then a second TURB with WLC and PDD, after 4 to 6 weeks. The number of tumors visualized in WLC and PDD and histology of the TURB specimen was recorded to perform a statistical analysis comparing both the 2 arms. Results A total of 151 patients were enrolled (hexaminolevulinate, n = 72; control, n = 79). The number of visualized tumors did not increase with PDD in the first or second TURB. During the second TURB, the residual tumor rate was not reduced in patients who had PDD during the first TURB. No significant difference was observed regarding the pattern of category and grade, the size, and the recurrence and progression risks during either the first or the second TURB. Conclusions In the setting of primary non–muscle-invasive bladder cancer with positive results on urine cytology, performing a second TURB allows to diagnose residual tumor in approximately half of the cases. This rate was not significantly reduced by the use of the PDD during the first TURB.

Objectifs Le cancer testiculaire est la premiere cause de cancer chez l’homme âge de 20 a 34 ans. Les tumeurs germinales non seminomateuses metastatiques sont traites par un curage lombo-aortique lorsqu’il persiste des masses residuelles apres chimiotherapie. L’abord cœlioscopique s’associe a une reduction des complications per- et perioperatoire. L’objectif de notre etude est d’etudier la faisabilite et les resultats oncologiques du curage lombo-aortique par voie cœlioscopique. Methodes Il s’agit d’une etude retrospective mono-operateur de novembre 2000 a novembre 2017 portant sur une serie de 107 patients. Les voies d’abords etaient cœlioscopiques transperitoneales et retroperitoneales. Les curages etaient unilateraux ou bilateraux. Les tumeurs germinales seminomateuses ont ete exclues de l’etude. L’ensemble des images radiologiques ont ete relues. Parmi les patients, 73,5 % presentaient une tumeur germinale mixte. Les stades 2a, 2b, 2c representaient respectivement 21,5 %, 28 %, 11,2 % des patients. Les stades 3 representaient 24,3 % des patients. Les patients de pronostics bon, intermediaire, mauvais representaient respectivement 71,1 %, 15,9 %, 13 %. La taille mediane selon le grand axe de la masse residuelle etait de 30 mm [10–134]. Resultats La duree mediane de suivi etait de 46,9 mois [1 ; 203]. Un abord transperitoneale et retroperitoneale etait realise chez 31,7 % et 66,3 % des patients. Le curage etait unilaterale dans 74,7 % des cas avec une duree operatoire mediane de 186 minutes [90–540] et bilaterale dans 25,2 % et une duree operatoire mediane de 254 minutes [138–489]. Le taux de conversion etait de 6,5 %. Parmi les patients, 17,2 % ont presente des complications postoperatoires precoces. La duree mediane d’hospitalisation etait de 4 jours [1 ; 26]. Des ejaculations antegrades etaient presentes chez 71,1 % des patients. Parmi les patients, 7,7 % ont presente une recidive tumorale, 2,8 % dans le template. L’intervalle de recidive median etait de 9,5 mois [1–20]. Au terme du suivi 94,4 % des patients etaient consideres vivant sans maladie. Conclusion Le curage lombo-aortique par voie cœlioscopique, realise dans un centre expert, est une technique faisable offrant une faible morbidite et de tres bons resultats oncologiques.

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.

Key points 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.

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.

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 ( 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.

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: Papillary histology accounts for 10-15% of renal cell carcinoma (RCC), and treatment options for patients with this subtype are limited. The RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe; ClinicalTrials.gov, NCT00688753) study evaluated first-line everolimus in patients with papillary metastatic RCC (mRCC). Methods: This phase 2 trial enrolled previously untreated patients with type 1 or type 2 papillary mRCC. Papillary histology was confirmed by central review and was performed for every patient. Patients received oral everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS) rate at 6 months among the first 44 patients of the per protocol (PP) population. Secondary end-points included PFS, tumour response, overall survival (OS), and safety. Findings: Analysis sets included safety (NZ 92; 100%), intent-to-treat (ITT) (n=88), and PP populations (n = 46). In the safety population, most patients were men (78%) and the mean age was 60 years (range 23-84). Papillary histology was confirmed in 78% of patients (type 1, 32%; type 2, 64%; missing information, 4%). PFS rate at 6 months was 34% (80% confidence interval [CI] 25-45). In the ITT population, median PFS was 4.1 months (95% CI 3.6-5.5), 65% of patients achieved stable disease, and median OS was 21.4 months (95% CI 15.4-28.4). Among patients with type 1 or type 2 histology, median PFS was 7.9 months (95% CI 2.1 -11.0) and 5.1 months (95% CI 3.3-5.5), respectively, and median OS was 28.0 months (95% CI 7.6-not estimable) and 24.2 months (95% CI 15.8-32.8), respectively. Common grade > 2 adverse events were asthenia (13%), anaemia (7%), and fatigue (5%). Interpretation: Results of this large prospective study in papillary mRCC demonstrated that everolimus provides some clinical benefit to this patient population and highlight the need for central pathological review of this rare tumour. (C) 2016 Elsevier Ltd. All rights reserved.

Radiotherapy combined with androgen-deprivation therapy (ADT) is superior to radiotherapy alone in localised prostate cancer; however, data comparing ADT alone are somewhat limited.To compare 3-yr ADT plus radiotherapy with ADT alone in locally advanced prostate cancer patients.A multicentre randomised open controlled phase 3 trial in 264 histologically confirmed T3-4 or pT3N0M0 prostate cancer patients randomised from March 2000 to December 2003.ADT (11.25mg subcutaneous depot injection of leuprorelin every 3 mo for 3 yr) plus external-beam radiotherapy or ADT alone. Flutamide (750 g/d) was administered for 1 mo.The primary objective was 5 yr progression-free survival (PFS) according to clinical or biologic criteria, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and the newer (Phoenix) definition (nadir plus 2 ng/ml), by intention to treat. Secondary objectives included time to locoregional recurrence and distant metastases, and overall and disease-specific survival. Our Analyses: intent-to-treat analysis, multivariate analyses using a Cox model with a 5% threshold from univariate analysis, and Kaplan-Meier estimates.ADT alone was administered to 130 patients and combined therapy to 133. With a median follow-up of 67 mo, 5-yr PFS was 60.9% for combined therapy versus 8.5% with ADT alone (ASTRO; p0.0001), and 64.7% versus 15.4%, respectively, for Phoenix (p0.0011). Locoregional progression was reported in 9.8% of combined-therapy patients versus 29.2% with ADT alone (p0.0001) and metastatic progression in 3.0% versus 10.8%, respectively (p0.018). Overall survival was 71.4% with combined therapy versus 71.5% with ADT alone; disease-specific survival was 93.2% versus 86.2%. Limitations included the relatively small population and a relatively short follow-up period.Combined therapy strongly favoured improved PFS, locoregional control, and metastasis-free survival. Longer follow-up is needed to assess the potential survival impact.

Study Type – Therapy (retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The more that bladder cancer progresses from the urothelium to the outside of the bladder the worse the prognosis. To date, the use of adjuvant chemotherapy has not been completely defined. The present study clarifies the prognosis and benefits of adjuvant chemotherapy for different stages of bladder cancer that invade perivesical fat. OBJECTIVE • To assess the prognosis of pT2b, pT3a and pT3b bladder cancers after radical cystectomy (RC) in order to define potential situations where chemotherapy may be of benefit. PATIENTS AND METHODS • Between 1985 and 2009, 903 patients underwent a RC and pelvic bilateral lymphadenectomy in an Institutional Referral Centre. • In all, 87 patients (9.6%) had a pT2b tumour, 111 patients (12.3%) a pT3a tumour, and 129 patients (14.3%) a pT3b tumour. • The median (range) overall follow-up was 23 (1–350) months. • Overall (OS), disease-specific (DSS), metastases-free (MFS) and local recurrence-free survival (LRFS) was estimated and compared using Kaplan–Meier plots and log-rank test. RESULTS • The 5-year survivals pT2b and pT3a were similar for LRFS (86% vs 84%), MFS (69% vs 63%), DSS (72% vs 70%) and OS (66% vs 61%), and the prognosis was better than for pT3b stage tumours (69%, 44%, 40%, and 31% respectively). • In pN0 disease, MFS differences between pT2b–pT3a and pT3b tumours were not significant in patients who had received adjuvant chemotherapy (MSF of 87%, 69% and 56%, respectively) while they were significant in patients without adjuvant chemotherapy (MFS of 70%, 68% and 42%, respectively). CONCLUSIONS • Bladder cancers invading perivesical tissue macroscopically have a greater propensity to produce lymph node metastases, local recurrence, and have lower MFS, DSS, and OS. In pN0 disease, pT3b tumours may receive more benefit from adjuvant chemotherapy. • Our results could be a useful for selecting patients for adjuvant chemotherapy.

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.

Objectifs L’interpretation histologique des pieces de prostatectomie radicale a pour but de confirmer la presence d’un adenocarcinome prostatique, d’en preciser la stadification : pTNM, score de Gleason et etat des marges d’exerese chirurgicale. Ces criteres sont parfois sujets a des interpretation individuelles inter-pathologistes avec des coefficient kappa variant de 0,2 a 0,9. Nous rapportons les resultats de la lecture centralisee des foyers index (plus haut stade et/ou de plus haut grade) des pieces de prostatectomie radicale de l’etude ANDROCAN. Methodes Les pathologistes des centres ayant participe a l’etude ANDROCAN ont transmis pour relecture centralise les lames du foyer index des pieces de prostatectomies radicales (1494 cas sur les 1516 inclus). Les deux pathologistes experts en uropathologie (VM, CR) ont relus de maniere anonymes les lames transmises et ont precise pour chaque cas le score de Gleason, le stade pTNM (2010) et l’etat des marges. En cas de discordance entre les deux relecteurs, une troisieme lecture au microscope a double tete a ete effectuee afin d’obtenir un consensus. Le coefficient de correlation Kappa a ete calcule pour evaluer la reproductibilite interobservateur. Resultats La concordance dans l’interpretation du score de Gleason exact (n = 1211) est de 36,5 % (Kappa = 0,035) avec une sous-evaluation du score dans 24,8 % des cas et une surevaluation du score dans 27,2 % des cas. En regroupant les cas en score de Gleason ≤ 6 ; 3 + 4 ; 4 + 3 et ≥ 8 (n = 1190), la concordance est de 36,8 % (Kappa = 0,025). La concordance pour la predominance de grade 4 et/ou 5 a ete de 57 % (Kappa = –0,003). L’analyse du stade pathologique effectuee dans 1342 cas retrouve une concordance dans 93,5 % des cas (Kappa = 0,86) avec une sous-evaluation du stade dans 2.2 % et une surevaluation du stade dans 4,2 % des cas. L’analyse des marges evaluable pour 1144 cas a montre une concordance dans 96,5 % des cas avec une sous-estimation des marges dans 5,8 % et une sur-estimation dans 16,6 % des cas (Kappa = 0,92) Tableau 1 , Tableau 2 . Conclusion Nos resultats montrent qu’en termes d’analyse interobservateur les pathologistes ayant participe a cette etude ont des coefficient de correlation excellents pour l’evaluation du stade et des marges, superieurs a ceux rapportes dans la litterature (Kappa = 0,58–0,82) mais que l’evaluation du SG et du pourcentage de grade 4/5 reste encore problematique.

Resume La tumeur trichilemmale proliferante (TTP) est une tumeur rare, d’evolution lente, prolongee, le plus souvent benigne, pouvant cependant presenter un potentiel evolutif pejoratif. La TTP survient le plus souvent chez les femmes âgees, au niveau du cuir chevelu ; d’autres localisations ont ete observees. Nous rapportons un cas de TTP, particulier par sa localisation dans la region ischio-rectale, qui aurait pu faire porter le diagnostic de carcinome epidermoide.

Translocation renal cell carcinomas represent a distinct clinicopathological entity. Studying the natural history, biological behavior and potential prognostic factors are crucially warranted.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.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.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.

Resume En 2009, le cancer de la prostate a fait l’objet de nombreuses communications dans les congres internationaux d’urologie, d’oncologie et de radiotherapie. L’evenement majeur a ete la presentation des resultats des etudes de depistage de masse europeenne ERSPC et americaine PLCO. Plusieurs communications concernent la prevention, l’histoire naturelle de la maladie et les nouveaux marqueurs tumoraux comme le PCa3 et le gene de fusion TMPRSS2 : ERG. L’hormonotherapie adjuvante a ete evaluee chez les patients a haut risque de recidive. L’association hormonotherapie-radiotherapie permettrait de reduire la recidive biologique, la mortalite specifique et la mortalite globale des patients porteurs d’une tumeur localement avancee. Le THI pourrait etre une option chez les patients metastatiques hormono-sensibles. L’interet du denosumab et du toremifene a ete evalue dans la prevention du risque fracturaire sous hormonotherapie. Le mecanisme de proliferation tumorale en situation d’echappement hormonal a ete precise et 2 nouvelles molecules l’abiraterone et le MDV 3100 apparaissent prometteuses.

Resume Tres peu d’etudes ont ete publiees concernant les resultats de la prostatectomie totale (PT) chez le patient âge. Les rares donnees disponibles suggerent que l’âge avance n’augmente pas le taux de mortalite ou de morbidite postoperatoire, sous reserve d’une selection etroite des patients. De meme, les resultats carcinologiques de la PT sont comparables entre les patients de plus de 70 ans et les patients plus jeunes. Seul le risque d’incontinence semble accru, avec un impact potentiel sur la qualite de vie. Il n’existe pas d’etude comparant les differents traitements curatifs du cancer de la prostate (PT, radiotherapie externe, curietherapie, surveillance active) dans la population âgee. Le benefice en termes de survie ne peut etre precise.

Prostate cancer (PaC) is a significant health problem. Elderly have the highest incidence of the disease as age is its strongest risk factor. Despite its complications, the use of androgen suppression in aging patients with prostate cancer has become extremely frequent with probable excess. However, some of these complications carry specific mortality and all of them have a negative impact on quality of life. It is critical to perform a geriatric assessment, concerning physical, mental and social items, before to consider androgen suppression in this population. Indications of androgen suppression for the treatment of prostate cancer follow the guidelines of CCAFU. Delayed treatment deserves a special attention when possible. Treatment modalities are no specific to the elderly, but complications have to be anticipated with preventive measures. Intermittent androgen suppression should be considered with caution. Close follow up will focus on the diagnosis of adverse effects of androgen suppression.

Resume L’hydatidose est une anthropozoonose largement repandue, touchant le foie, le poumon et d’autres organes. Nous decrivons ici le cas de volumineux kyste hydatique retroperitoneal, localisation particulierement rare, dont le diagnostic a ete pose grâce a des prelevements sanguins et des investigations radiologiques. Une incision de greffe renale etendue en sous-costale droit a ete effectuee. La paroi du kyste a ete partiellement excisee. Le patient a recu en pre-, per-, et postoperatoire de l’albendazole en comprimes a la dose de 15 mg/kg par jour. La dose totale a ete administree pendant trois semaines (une semaine avant et deux semaines apres la chirurgie) avec une surveillance biologique hepatique. Lors du bilan d’une masse retroperitoneale, le diagnostic de kyste hydatique doit etre garde a l’esprit, notamment chez les patients provenant de regions d’endemie. Ces kystes peuvent etre traites efficacement par chirurgie.

Prostate biopsies remain the only way to confirm the presence of prostate cancer. Nevertheless, the ideal number of biopsies needed to establish the diagnosis is prone to controversy. The current European guidelines recommend 12 sextant biopsies. Few recommendations concerning how the biopsies should be handled have been published. In France, in order to avoid the loss of histological specimens, it was strongly recommended to transmit each core biopsy to the pathology department in an independent container. Performing a large number of biopsies means an increase in the number of containers transmitted and consequently a technical overload of the transmission network, which occurs without any financial counterpart. Since the current tarification system establishes cost allotment by activity, there is no room for an increased technical workload schedule. New approaches must be developed in order to increase productivity. The main aim of our study was to search for answers to the question whether it would be possible to use only one container per sextant irrespective of the number of biopsies performed. For this purpose, we performed various series of one, two, three, four or six biopsies from fresh total prostatectomies with an automatic prostate biopsy gun. All the biopsies were paraffin embedded after a 4% formalin fixative procedure. All the cores were measured after fixing, and on HES slides. The 48 series were as follow: 10 cases with one core, 16 cases with two cores, 13 cases with three cores, five cases with four cores and three cases with six cores. The average length of each core before inclusion varied from 11,8mm to 16,3mm. The average length on HES slides from 9,7 to 11,5mm. A significant difference was observed only for the blocks containing six biopsies (p=0.02). Inclusion of one to three cores from each sextant, did not lead to a loss of information or loss of chances for the patient.

The histological grading system of prostate cancer proposed by David Gleason in 1966 remains, more than 40 years after its princeps use, an essential tool of communication between the pathologists and urologists. We present here the principal modifications of this score proposed in 2005 by the International Society of Uropathology.

The identification of fusion genes provides new insights into the initial mechanisms of molecular events implicated in the tumorigenesis of prostate cancer. The presence of TEMPRSS2-ETS fusion in up to half of all human prostate cancers makes it perhaps the most common genetic rearrangement in human epithelial tumors. Some data suggest that TMPRSS2-ERG fusion prostate cancers have a more aggressive phenotype which may affect cancer progression and outcome in localized tumors treated with prostatectomy. This discovery should pave the way towards future targeted therapies.

The two major genes responsible for autosomal dominant polycystic kidney disease and complex tuberous sclerosis are located on chromosome 16 at position 16p13.3, separated by only a few nucleotides. A simultaneous loss of both genes has been termed "the TSC2/PKD1 contiguous gene syndrome". It has been described essentially in young children. We report 2 new cases in French adults, in whom the diagnosis has been made fortuitously on the macroscopic and microscopic examination of the nephrectomy specimen. This diagnosis should be considered for the association of a polycystic kidney disease and numerous angiomyolipomas. It is necessary to set up a specific follow-up of both diseases.

Although Bacillus Calmette-Guérin (BCG) instillations are considered as the adjuvant treatment of choice for stage Ta-T1 grade G3 bladder tumours, there is no consensus for a predictive factor to assess BCG success. This study attempted to evaluate if heat shock proteins (HSPs) could be useful predictive markers in BCG responses.Thirty-three primary resected G3 superficial bladder tumours were included in the study. All patients received adjuvant BCG instillations. The mean follow-up was 56 mo (range: 24-132 mo). HSP expression was evaluated by immunochemistry.In the 33 patients, 18 had no recurrence (group 1), 9 had recurrence with no muscular invasion (group 2), and 6 had an invasive recurrence (group 3). A significant correlation was found between lack of expression of HSP90 and BCG response: the mean HSP expression was 92.7%, 84.4%, and 26.7% for groups 1, 2 and 3 tumours, respectively (p0.0001). For the 6 patients who did not positively respond to BCG, HSP expression was40%. All the tumours with a HSP90 expression40% positively responded to BCG, corresponding to group 1 or 2 patients. In contrast, HSP60 expression was not correlated to the BCG response.HSP90 could be considered as a very promising marker to assess BCG treatment response. Low HSP90 expression (40%) could be useful to predict BCG failure and early stage cystectomy could be proposed for these selected patients with primary high-risk grade 3 superficial bladder tumours.

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 towhat can be found inmainland France or in African Americans. These findings may be ascribed to low tobacco consumption aswell as togenetic factors. Systematic screening in patients of African Caribbean origin should be prescribed.

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. Clin Cancer Res; 21(6); 1329–39. ©2015 AACR.

PURPOSE To compare histological features of prostate cancer according to both obesity, defined by a body mass index (BMI) ≥30 kg/m2, and androgenic status in patients who underwent radical prostatectomy. MATERIALS AND METHODS Between March 2007 and September 2013, clinical, pathological and biological data were prospectively collected for patients referred for radical prostatectomy in a single European center. Preoperative total testosterone (TT) and bioavailable testosterone (bioT) serum determinations were performed. The threshold for hypogonadism was set at TT

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

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

OBJECTIVE To investigate the potential utility of a new combined immunostaining technique for diagnosing prostate cancer from histological analysis of needle biopsy specimens. MATERIALS AND METHODS Tissue was immunostained with a combination of antibodies against a basal cell marker (p63), and an enzyme commonly overexpressed in prostate cancer (p504s), on 63 small prostate cancer foci (

BACKGROUND The Fuhrman system is the most widely used nuclear grading system for renal cell carcinoma (RCC). Although Fuhrman nuclear grade is widely accepted as a significant prognostic factor, its reproducibility, as reported in the limited number of series available in the literature, appears to be low. METHODS Between 1980 and 1990, 255 cases of RCC (pT1–3bN0M0) were treated with radical nephrectomy at the Department of Urology, University Hospital, Strasbourg, France. In a retrospective multicenter study, 3 pathologists independently classified 241 of these 255 cases according to the Fuhrman grading system. The authors searched for optimal interobserver agreement by collapsing the grading system to a three-tiered scheme and then to a two-tiered scheme. In addition, overall survival curves were generated according to the classic four-tiered scheme and also according to the best collapsed scheme. The kappa index was used to assess the level of agreement between each pair of observers, and the Cox model was used for multivariate survival analyses. RESULTS The mean interobserver κ value was 0.22 (range, 0.09–0.36). The best concordance was obtained by collapsing to a system in which low-grade (Grade 1–2) disease was compared with high-grade (Grade 3–4) disease. Doing so improved the mean interobserver κ value to 0.44 (range, 0.32–0.55). Fuhrman grade was an independent prognostic factor for all 3 pathologists (P = 0.01, P < 0.0001, and P = 0.004, respectively), and nuclear grade continued to have independent prognostic value after the optimal collapsing algorithm was performed (P = 0.004, P = 0.0003, and P = 0.005). CONCLUSIONS Collapsing of the Fuhrman grading system to a two-tiered scheme led to an improvement in interobserver agreement while preserving the independent prognostic value of nuclear grade. Cancer 2005. © 2004 American Cancer Society.