Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer. Issue 6 (26th April 2014)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: International journal of cancer. Volume 135:Issue 6(2014:Sep. 15)
• Page Start: 1369
• Page End: 1380
• Publication Date: 2014-04-26
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28784
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Despite a multitude of p53 immunohistochemistry (IHC) studies, data on the combined effect of nuclear p53 protein accumulation and <italic>TP53</italic> 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. <italic>TP53</italic> 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. <italic>TP53</italic> deletions occurred in 14.8% of cancers. Both deletions and protein accumulation were linked to unfavorable tumor phenotype and prostate specific antigen (PSA) recurrence (<italic>p</italic> < 0.0001 each). The combination of both methods revealed subgroups with remarkable differences in their clinical course. Tumors with either <italic>TP53</italic> 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 (<italic>p</italic> < 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 (<italic>p</italic> < 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 <italic>TP53</italic> 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.</p> </abstract>