Multicenter Validation of Histopathologic Tumor Regression Grade After Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Carcinoma

Response classification after neoadjuvant chemotherapy in muscle-invasive bladder carcinoma is based on the TNM stage at radical cystectomy. We recently showed that histopathologic tumor regression grades (TRGs) add prognostic information to TNM. Our aim was to validate the prognostic significance of TRG in muscle-invasive bladder cancer in a multicenter setting. We enrolled 389 patients who underwent cisplatin-based chemotherapy before radical cystectomy in 8 centers between 2010 and 2016. Median follow-up was 2.2 years. TRG was determined in radical cystectomy specimens by local pathologists. Central pathology review was conducted in 20% of cases, which were randomly selected. The major response was defined as ≤pT1N0. The remaining patients were grouped into partial responders (≥ypT2N0-3 and TRG 2) and nonresponders (≥ypT2N0-3 and TRG 3). TRG was successfully determined in all cases, and interobserver agreement in central pathology review was high (κ=0.83). After combining TRG and TNM, 47%, 15%, and 38% of patients were major, partial, and nonresponders, respectively. Combination of TRG and TNM showed significant prognostic discrimination of overall survival (major responder: reference; partial responder: hazard ratio 3.5 [95% confidence interval: 1.8-6.8]; nonresponder: hazard ratio 6.1 [95% confidence interval: 3.6-10.3]). This discrimination was superior compared with TNM staging alone, supported by 2 goodness-of-fit criteria (P=0.041). TRG is a simple, reproducible histopathologic measurement of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer. Integrating TRG with TNM staging resulted in significantly better prognostic stratification than TNM staging alone

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

Caractérisation immunohistochimique des principaux types histologiques de tumeurs épithéliales rénales étudiées par tissue-arrays sur une série de 363 cas

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

Les tumeurs rénales hybrides oncocytome / chromophobe (caractéristiques clinicopathologiques et genomiques d'une série de 13 cas)

Les tumeurs hybrides oncocytome/chromophobe (THOC) sont des tumeurs rénales de description récente montrant des caractéristiques morphologiques hybrides entre l oncocytome rénal (OR) et le carcinome chromophobe (CChr). Leur nature précise reste à ce jour indéterminée. Décrire les caractéristiques clinico-pathologiques des THOC et déterminer leur profil génomique.583 tumeurs rénales appartenant au groupe OR/CChr collectées entre 2000 et 2010 et provenant de 5 centres ont été revues de façon rétrospective. Une analyse histologique standard était réalisée, associée à une coloration de Hale et une immunohistochimie cytokératine 7 (CK7) dans les cas de diagnostic difficile entre OR et CChr. Au final, 13 tumeurs inclassables étaient considérées comme THOC. L analyse génomique était effectuée par array-CGH à partir de l ADN extrait sur prélèvement congelé. L âge moyen au diagnostic était de 68 ans. La taille tumorale moyenne était de 2,5 cm. Aucun des patients n a présenté de récidive. Sur le plan histologique, les THOC montraient soit des territoires intriqués de cellules d aspect oncocytaire et chromophobe, soit des cellules d aspect hybride. La coloration de Hale était apicale dans 50 à 100% des cellules, et la CK7 était exprimée dans 10 à 100% des cellules. Le profil génomique était équilibré dans 7 cas, et montrait un nombre limité de pertes ou gains chromosomiques dans les autres tumeurs. Dans aucun cas les pertes chromosomiques caractéristiques du CChr n étaient retrouvées. Ces données suggèrent que les THOC n ont pas de lien avec le CChr, et que ces tumeurs pourraient représenter un variant d ORPARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

ETUDE COMPARATIVE DE L'EXPRESSION DE KI-67 ET DE P53, ET DES DELETIONS DE 24 MARQUEURS MICROSATELLITES DANS UNE SERIE DE 44 TUMEURS VESICALES UROTHELIALES

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Le carcinome rénal papillaire à cellules claires (caractérisation d'une nouvelle entité de tumeur rénale)

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Clear-cell papillary renal cell carcinoma: 24 cases of a distinct low-grade renal tumor and a comparative genomic hybridization array study of 7 cases.

International audienceAim: To report clinicopathological and genomic characteristics of clear-cell papillary renal carcinoma (ccpRCC), a rare, recently characterized renal tumor entity. Methods and results: Twenty-four renal tumors identified as ccpRCC were gathered. Data from comparative genomic hybridization on microarrays (array-CGH) were obtained for 7 of them. Most tumors (58%) occurred in the absence of renal disease. Mean patient age was 58.1 years. Tumors were small (mean size: 2.4 cm) and classified as pT1a. Histological characteristics consisted of tubes and papillae lined by a single layer of small clear cells harboring low-grade nuclei (Fuhrman grade 1 or 2). Architectural variations, with compact areas (41% of cases) and a micro- or macrocystic pattern (67% of cases) were frequently observed. Immunostaining demonstrated diffuse, strong expression of cytokeratin 7 and vimentin, whereas CD10, racemase, RCC antigen, TFE3 and TFEB were consistently negative. In 7 tumors, array-CGH detected no chromosome imbalances. Conclusion: ccpRCC were differentiated from other renal neoplasms by the specific association of histopathological and immunohistochemical features, without characteristic genomic imbalances. Clinical, histopathological and genomic data suggested that this tumor have low potential for malignancy