Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer
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Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer. / Kluth, Martina; Harasimowicz, Silvia; Burkhardt, Lia; Grupp, Katharina; Krohn, Antje; Prien, Kristina; Gjoni, Jovisa; Hass, Thomas; Galal, Rami; Graefen, Markus; Haese, Alexander; Simon, Ronald; Hühne-Simon, Julia; Koop, Christina; Korbel, Jan; Weischenfeld, Joachim; Huland, Hartwig; Sauter, Guido; Quaas, Alexander; Wilczak, Waldemar; Tsourlakis, Maria Christina; Minner, Sarah; Schlomm, Thorsten.
in: INT J CANCER, Jahrgang 135, Nr. 6, 13.02.2014, S. 1369-1380.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung
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TY - JOUR
T1 - Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer
AU - Kluth, Martina
AU - Harasimowicz, Silvia
AU - Burkhardt, Lia
AU - Grupp, Katharina
AU - Krohn, Antje
AU - Prien, Kristina
AU - Gjoni, Jovisa
AU - Hass, Thomas
AU - Galal, Rami
AU - Graefen, Markus
AU - Haese, Alexander
AU - Simon, Ronald
AU - Hühne-Simon, Julia
AU - Koop, Christina
AU - Korbel, Jan
AU - Weischenfeld, Joachim
AU - Huland, Hartwig
AU - Sauter, Guido
AU - Quaas, Alexander
AU - Wilczak, Waldemar
AU - Tsourlakis, Maria Christina
AU - Minner, Sarah
AU - Schlomm, Thorsten
N1 - © 2014 UICC.
PY - 2014/2/13
Y1 - 2014/2/13
N2 - Despite a multitude of p53 immunohistochemistry (IHC) studies, data on the combined effect of nuclear p53 protein accumulation and TP53 genomic inactivation are lacking for prostate cancer. A tissue microarray including 11,152 prostate cancer samples was analyzed by p53 IHC and fluorescence in situ hybridization. Nuclear p53 accumulation was found in 10.1% of patients including 1.4% with high-level and 8.7% with low-level immunostaining. TP53 sequencing revealed that 17 of 22 (77%) cases with high-level p53 immunostaining, but only 3% (1 of 31) low-level p53 cases carried putative dominant-negative mutations. TP53 deletions occurred in 14.8% of cancers. Both deletions and protein accumulation were linked to unfavorable tumor phenotype and prostate specific antigen (PSA) recurrence (p < 0.0001 each). The combination of both methods revealed subgroups with remarkable differences in their clinical course. Tumors with either TP53 deletion (14%) or low-level p53 positivity (8.7%) had identical risks of PSA recurrence, which were markedly higher than in cancers without p53 alterations (p < 0.0001). Tumors with both p53 deletion and low-level p53 positivity (1.5%) had a worse prognosis than patients with only one of these alterations (p < 0.0001). Tumors with strong p53 immunostaining or homozygous inactivation through deletion of one allele and disrupting translocation involving the second allele had the worst outcome, independent from clinical and pathological parameters. These data demonstrate a differential clinical impact of various TP53 alterations in prostate cancer. Strong p53 immunostaining-most likely accompanying dominant negative or oncogenic p53 mutation-has independent prognostic relevance and may thus represent a clinical useful molecular feature of prostate cancer.
AB - Despite a multitude of p53 immunohistochemistry (IHC) studies, data on the combined effect of nuclear p53 protein accumulation and TP53 genomic inactivation are lacking for prostate cancer. A tissue microarray including 11,152 prostate cancer samples was analyzed by p53 IHC and fluorescence in situ hybridization. Nuclear p53 accumulation was found in 10.1% of patients including 1.4% with high-level and 8.7% with low-level immunostaining. TP53 sequencing revealed that 17 of 22 (77%) cases with high-level p53 immunostaining, but only 3% (1 of 31) low-level p53 cases carried putative dominant-negative mutations. TP53 deletions occurred in 14.8% of cancers. Both deletions and protein accumulation were linked to unfavorable tumor phenotype and prostate specific antigen (PSA) recurrence (p < 0.0001 each). The combination of both methods revealed subgroups with remarkable differences in their clinical course. Tumors with either TP53 deletion (14%) or low-level p53 positivity (8.7%) had identical risks of PSA recurrence, which were markedly higher than in cancers without p53 alterations (p < 0.0001). Tumors with both p53 deletion and low-level p53 positivity (1.5%) had a worse prognosis than patients with only one of these alterations (p < 0.0001). Tumors with strong p53 immunostaining or homozygous inactivation through deletion of one allele and disrupting translocation involving the second allele had the worst outcome, independent from clinical and pathological parameters. These data demonstrate a differential clinical impact of various TP53 alterations in prostate cancer. Strong p53 immunostaining-most likely accompanying dominant negative or oncogenic p53 mutation-has independent prognostic relevance and may thus represent a clinical useful molecular feature of prostate cancer.
U2 - 10.1002/ijc.28784
DO - 10.1002/ijc.28784
M3 - SCORING: Journal article
C2 - 24523142
VL - 135
SP - 1369
EP - 1380
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 6
ER -
