The World Health Organization 1973 classification system for grade is an important prognosticator in T1 non-muscle-invasive bladder cancer

467 Background: There is an unmet need for a comprehensive genomic characterization of non muscle invasive bladder cancer (NMIBC). NMIBC comprise over 70% of all bladder cancers at presentation. They have highly variable clinical behavior that is not always adequately predicted on the basis of their histological grade (2004 World Health Organization low and high grade, LG-HG). The discrepancy between phenotype and genotype is compounded further by interobserver variability in pathological grading. We have previously established methods for whole transcriptome RNAseq from formalin fixed paraffin embedded tissues (FFPE). Methods: Whole transcriptomic analysis of 110 NMI FFPE BC both LG and HG was performed incorporating messenger RNA expression, splice variants, gene fusion, and pathway perturbation. We used a discovery (n = 40) and a validation cohort (n = 70). These data were integrated and tested for correlation with both pathological grading and clinical outcomes. Grade Risk Index (GRI) score quantifying how closely a patient's transcriptome is related to a reference set of LG NMIBC samples was established. Conventional pathological grading was reviewed by 3 different expert uro-pathologists and interobserver variability calculated. Results: Unsupervised clustering of data from RNA sequencing uncovered classification of three robust - - nonoverlapping, prognostically significant subtypes of NMIBC with distinct GRIs and signatures. When applied by expert pathologists, interobserver variability in histological grading was observed in 17.5%. In the intermediate group (GRI 0.13 to 0.19), pathologists disagreed in 37.5% whether BC was LG or HG. HG NMIBC clustered with MIBC. LG NMIBC in the intermediate GRI group included either very bulky tumors or extremely rare metastatic LG BC (n = 4). HG disease was associated with a shift in BMP signaling and a germ stem cell-like phenotype. Multiple components of the centromere complex and APOBEC3B were upregulated in HG BC. FGFR3::TACC3 fusion events were observed in LG NMIBC only (11.5%). Conclusions: Whole transcriptomic sequencing data delineated three molecular classes of NMIBC.

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New Italian guidelines on bladder cancer, based on the World Health Organization 2004 classification

BJU International ◽

10.1111/j.1464-410x.2010.09324.x ◽

2010 ◽

Vol 106 (2) ◽

pp. 168-179 ◽

Cited By ~ 5

Author(s):

Paolo Puppo ◽

Giario Conti ◽

Francesco Francesca ◽

Alberto Mandressi ◽

Angelo Naselli ◽

...

Keyword(s):

Bladder Cancer ◽

World Health Organization ◽

World Health ◽

The World ◽

Health Organization

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Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines according to the biopharmaceutics classification system

European Journal of Pharmaceutics and Biopharmaceutics ◽

10.1016/j.ejpb.2004.03.001 ◽

2004 ◽

Vol 58 (2) ◽

pp. 265-278 ◽

Cited By ~ 440

Author(s):

Marc Lindenberg ◽

Sabine Kopp ◽

Jennifer B Dressman

Keyword(s):

World Health Organization ◽

Classification System ◽

Biopharmaceutics Classification System ◽

Essential Medicines ◽

World Health ◽

Organization Model ◽

The World ◽

Health Organization ◽

Biopharmaceutics Classification

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Clinical outcomes of muscle invasive bladder Cancer according to the BASQ classification

BMC Cancer ◽

10.1186/s12885-019-6042-1 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 4

Author(s):

Hyeong Dong Yuk ◽

Chang Wook Jeong ◽

Cheol Kwak ◽

Hyeon Hoe Kim ◽

Kyung Chul Moon ◽

...

Keyword(s):

Bladder Cancer ◽

Classification System ◽

Expression Patterns ◽

Treatment Strategies ◽

Invasive Bladder Cancer ◽

Molecular Characteristics ◽

Muscle Invasive Bladder Cancer ◽

Cancer Specific Survival ◽

Muscle Invasive

Abstract Background We evaluated the clinical efficacy and prognosis of muscle-invasive bladder cancer according to the basal/squamous-like (BASQ) classification system based on immunohistochemical staining [CK5/6(+), CK14(+), GATA3(−), and FOXA1(−)]. Methods One hundred patients diagnosed with muscle-invasive bladder cancer (cT2-4 N0-3 M0) were included in the study. All patients underwent radical cystectomy after transurethral removal of bladder tumor. Immunostaining was performed for CK5/6, CK14, FOXA1, and GATA3 antibodies on tissue microarray slides, and expression patterns were quantitatively analyzed using a scanning program. Results The median follow-up time was 77.4 (interquartile range: 39–120.9) months. The mean age of the patients was 65.1 ± 11.2 years. FOXA1 or CK14 expression greater than 1% was respectively positively and negatively correlated with overall survival (OS; p = 0.011 and p = 0.042, respectively), cancer-specific survival (CSS; p = 0.050 for both), and recurrence-free survival (RFS; p = 0.018 and p = 0.040, respectively). For CK5/6+ and GATA3- or FOXA1- expression, 10% CK5/6+ cells were negatively correlated with OS (p = 0.032 and p = 0.039, respectively) and with RFS in combination with FOXA1- only (p = 0.050). Conclusions In this study, CK14 expression was associated with a poor prognosis. The new classification system of bladder cancer based on molecular characteristics is expected to helpful tool for the establishment of personalized treatment strategies and associated prediction of therapeutic responses.

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