TY - JOUR
TI - Activation of extracellular regulated kinases ERK12 predicts poor prognosis in urothelial bladder carcinoma and is not associated with B-Raf gene mutations
AU - Karlou, M.
AU - Saetta, A.A.
AU - Korkolopoulou, P.
AU - Levidou, G.
AU - Papanastasiou, P.
AU - Boltetsou, E.
AU - Isaiadis, D.
AU - Pavlopoulos, P.
AU - Thymara, I.
AU - Thomas-Tsagli, E.
AU - Patsouris, E.
JO - EMC - Toxicologie-Pathologie
PY - 2009
VL - 41
TODO - 4
SP - 327-334
PB - LIBRAPHARM/INFORMA HEALTHCARE
SN - null
TODO - 10.1080/00313020902885011
TODO - B Raf kinase;  mitogen activated protein kinase 1;  mitogen activated protein kinase 3;  B Raf kinase;  BRAF protein, human;  FGFR3 protein, human;  fibroblast growth factor receptor 3;  mitogen activated protein kinase 1;  mitogen activated protein kinase 3, adult;  aged;  article;  bladder carcinoma;  cancer grading;  controlled study;  cytoplasm;  female;  gene mutation;  gene sequence;  human;  human tissue;  immunohistochemistry;  immunoreactivity;  major clinical study;  male;  multivariate analysis;  polymerase chain reaction;  statistical significance;  survival;  univariate analysis;  biosynthesis;  bladder tumor;  enzyme activation;  enzymology;  genetics;  Kaplan Meier method;  metabolism;  middle aged;  mutation;  pathology;  physiology;  prognosis;  single strand conformation polymorphism;  transitional cell carcinoma, Adult;  Aged;  Aged, 80 and over;  Carcinoma, Transitional Cell;  Enzyme Activation;  Female;  Humans;  Immunohistochemistry;  Kaplan-Meiers Estimate;  Male;  Middle Aged;  Mitogen-Activated Protein Kinase 1;  Mitogen-Activated Protein Kinase 3;  Mutation;  Polymerase Chain Reaction;  Polymorphism, Single-Stranded Conformational;  Prognosis;  Proto-Oncogene Proteins B-raf;  Receptor, Fibroblast Growth Factor, Type 3;  Urinary Bladder Neoplasms
TODO - Summary Aim: The analysis of the presence of B-Raf gene mutations in relation to ERK12 activation in bladder urothelial carcinoma UC, in order to determine their potential role in tumour aggressiveness and patients' survival. Methods: Polymerase chain reaction-single strand confirmation polymorphism PCR-SSCP and sequencing analysis were used for B-Raf gene mutation detection. pERK12 and FGFR3 expression were examined by immunohistochemistry in 152 and 116 primary UCs, respectively. Results: None of the cases displayed mutations in exon 15 of B-Raf gene. Nuclear or cytoplasmic pERK immunoreactivity was displayed in 99.3 and 96.7 of cases, respectively. pERK nuclear expression increased with histological grade and with T-category. Nuclear and cytoplasmic pERK expression was unrelated to FGFR3 expression. In univariate survival analysis of muscle-invasive carcinomas, advanced T-category and higher pERK nuclear expression p 0.018 adversely affected survival. However, multivariate analysis in non-invasive as well as in muscle-invasive carcinomas selected only T-category as a significant prognosticator. Conclusions: Our findings suggest that elevated pERK expression occurs in UCs in the absence of B-Raf mutations and is not correlated with FGFR3 over-expression. Moreover, it implicates ERK activation in the acquisition of a more aggressive phenotype. However, the assessment of pERK12 expression does not seem to add to the prognostic information provided by classical prognosticators. © 2009 Informa UK Ltd All rights reserved.
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