Details

Autor(en) / Beteiligte

• 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

Titel

Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer

Ist Teil von

• International journal of cancer, 2014-09, Vol.135 (6), p.1369-1380

Ort / Verlag

Hoboken, NJ: Wiley-Blackwell

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. What's New? Despite a multitude of p53 immunohistochemistry studies, data on the combined effect of nuclear p53 protein accumulation and TP53 genomic inactivation are lacking for prostate cancer. Here, a tissue microarray including 11,000 prostate cancer samples was analyzed by p53 immunohistochemistry and fluorescence in‐situ hybridization. The data demonstrate that different types of TP53 defects impact the clinical course of the disease differently. Strong nuclear p53 protein accumulation, or complete genomic inactivation through deletion of one allele and breakage of the second, characterized a patient subgroup with inferior outcome independently from other established prognostic parameters, thus potentially representing clinically useful molecular parameters.