Τίτλος:
Activation of extracellular regulated kinases ERK12 predicts poor prognosis in urothelial bladder carcinoma and is not associated with B-Raf gene mutations
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Karlou, M.
Saetta, A.A.
Korkolopoulou, P.
Levidou, G.
Papanastasiou, P.
Boltetsou, E.
Isaiadis, D.
Pavlopoulos, P.
Thymara, I.
Thomas-Tsagli, E.
Patsouris, E.
Περιοδικό:
EMC - Toxicologie-Pathologie
Εκδότης:
LIBRAPHARM/INFORMA HEALTHCARE
Λέξεις-κλειδιά:
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
DOI:
10.1080/00313020902885011
