PTEN deletions are related to disease progression and unfavourable prognosis in early bladder cancer
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PTEN deletions are related to disease progression and unfavourable prognosis in early bladder cancer. / 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.
in: HISTOPATHOLOGY, Jahrgang 63, Nr. 5, 01.11.2013, S. 670-7.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - PTEN deletions are related to disease progression and unfavourable prognosis in early bladder cancer
AU - Cordes, Inga
AU - Kluth, Martina
AU - Zygis, Dominika
AU - Rink, Michael
AU - Chun, Felix
AU - Eichelberg, Christian
AU - Dahlem, Roland
AU - Fisch, Margit
AU - Höppner, Wolfgang
AU - Wagner, Walter
AU - Doh, Ousman
AU - Terracciano, Luigi
AU - Simon, Ronald
AU - Wilczak, Waldemar
AU - Sauter, Guido
AU - Minner, Sarah
N1 - © 2013 John Wiley & Sons Ltd.
PY - 2013/11/1
Y1 - 2013/11/1
N2 - 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 pTaG1, 10.9% of pTaG2, 29.0% of pTaG3, 16.7% of pT1G2, 22.2% of pT1G3, 17.7% of pT2-4G2 and 20.9% of pT2-4G3 tumours (P = 0.0235). PTEN deletions were associated significantly with recurrences in pTa tumours (P = 0.0173), progression in pT1 tumours (P = 0.0016), but not with overall or cancer-specific survival in pT2 tumours. Multivariate analyses including grade and PTEN deletions revealed that PTEN deletions but not grade were associated independently with recurrence in pTa tumours (P = 0.0377) and progression in pT1 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.
AB - 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 pTaG1, 10.9% of pTaG2, 29.0% of pTaG3, 16.7% of pT1G2, 22.2% of pT1G3, 17.7% of pT2-4G2 and 20.9% of pT2-4G3 tumours (P = 0.0235). PTEN deletions were associated significantly with recurrences in pTa tumours (P = 0.0173), progression in pT1 tumours (P = 0.0016), but not with overall or cancer-specific survival in pT2 tumours. Multivariate analyses including grade and PTEN deletions revealed that PTEN deletions but not grade were associated independently with recurrence in pTa tumours (P = 0.0377) and progression in pT1 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Disease Progression
KW - Female
KW - Gene Deletion
KW - Humans
KW - Male
KW - Middle Aged
KW - Neoplasm Recurrence, Local
KW - PTEN Phosphohydrolase
KW - Prognosis
KW - Urinary Bladder Neoplasms
U2 - 10.1111/his.12209
DO - 10.1111/his.12209
M3 - SCORING: Journal article
C2 - 24004025
VL - 63
SP - 670
EP - 677
JO - HISTOPATHOLOGY
JF - HISTOPATHOLOGY
SN - 0309-0167
IS - 5
ER -