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PTEN deletions are related to disease progression and unfavourable prognosis in early bladder cancer
Author(s) -
Cordes Inga,
Kluth Martina,
Zygis Dominika,
Rink Michael,
Chun Felix,
Eichelberg Christian,
Dahlem Roland,
Fisch Margit,
Höppner Wolfgang,
Wagner Walter,
Doh Ousman,
Terracciano Luigi,
Simon Ronald,
Wilczak Waldemar,
Sauter Guido,
Minner Sarah
Publication year - 2013
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12209
Subject(s) - pten , bladder cancer , cancer research , tumor suppressor gene , biology , cancer , pathology , medicine , oncology , carcinogenesis , genetics , pi3k/akt/mtor pathway , apoptosis
Aims This study aimed to determine the prevalence and clinical significance of deletions of the tumour suppressor gene PTEN in bladder cancer. Methods and results A tissue microarray with 686 bladder cancers was analysed for PTEN deletions by fluorescence in‐situ hybridization. PTEN mutations were analysed in nine tumours with heterozygous PTEN deletion. Heterozygous PTEN deletions were present in 16.5% of tumours and were associated with grade ( P = 0.0024) and p53 status ( P = 0.0141), but not linked to stage ( P = 0.0965). PTEN deletions were seen in 5.8% of p T a G 1, 10.9% of p T a G 2, 29.0% of p T a G 3, 16.7% of p T 1 G 2, 22.2% of p T 1 G 3, 17.7% of p T 2–4 G 2 and 20.9% of p T 2–4 G 3 tumours ( P = 0.0235). PTEN deletions were associated significantly with recurrences in p T a tumours ( P = 0.0173), progression in p T 1 tumours ( P = 0.0016), but not with overall or cancer‐specific survival in p T 2 tumours. Multivariate analyses including grade and PTEN deletions revealed that PTEN deletions but not grade were associated independently with recurrence in p T a tumours ( P = 0.0377) and progression in p T 1 tumours ( P = 0.0030). No inactivating PTEN mutations were found. Conclusions PTEN is linked to aggressive tumour phenotype and to unfavourable outcome in early bladder cancer. Heterozygous PTEN loss, i.e. reduced PTEN gene dosage, might be sufficient to cause aggressive tumour behaviour in bladder cancer cells.