P53 mutations in advanced cancers: clinical characteristics, outcomes, and correlation between progression-free survival and bevacizumab-containing therapy

Mutations in the p53 gene are amongst the most frequent aberrations seen in human cancer. Our objective was to characterize the clinical characteristics associated with p53 mutation in patients with advanced cancer. We retrospectively reviewed and analyzed the clinical features and response to stand...

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Bibliographic Details
Published in:Oncotarget 2013-05, Vol.4 (5), p.705-714
Main Authors: Said, Rabin, Hong, David S, Warneke, Carla L, Lee, J Jack, Wheler, Jennifer J, Janku, Filip, Naing, Aung, Falchook, Gerald S, Fu, Siqing, Piha-Paul, Sarina, Tsimberidou, Apostolia M, Kurzrock, Razelle
Format: Article
Language:English
Subjects:
Angiogenesis Inhibitors - therapeutic use
Antibodies, Monoclonal, Humanized - therapeutic use
Bevacizumab
Disease-Free Survival
Female
Humans
Liver Neoplasms - epidemiology
Liver Neoplasms - secondary
Male
Middle Aged
Mutation
Neoplasms - drug therapy
Neoplasms - genetics
PTEN Phosphohydrolase - genetics
Research Papers
Retrospective Studies
Tumor Suppressor Protein p53 - genetics
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Summary:Mutations in the p53 gene are amongst the most frequent aberrations seen in human cancer. Our objective was to characterize the clinical characteristics associated with p53 mutation in patients with advanced cancer. We retrospectively reviewed and analyzed the clinical features and response to standard systemic therapy of 145 patients with documented tumor p53 mutational status (mutant-type [mtp53] vs. wild-type [wtp53]) referred to the Clinical Center for Targeted Therapy. Sixty-six (45.5%) patients had mtp53. Mutations in p53 occurred more frequently in older patients (p= 0.015) and in Caucasians (p=0.024). The incidence of liver metastases was 69.2% vs. 43%, p=0.002 in mtp53 and wtp53, respectively. PTEN loss by immunohistochemistry was found more frequently in mtp53-bearing tumors compared to wtp53 (33.3% vs. 10%, p=0.007). The best progression-free survival (PFS) on standard systemic therapy was significantly longer with bevacizumab-containing regimens as compared to non-bevacizumab containing regimen in patients with mtp53 (median 11.0 [95% CI 5.9-16.0], n=22 vs. 4.0 months [95% CI 3.6-5.7], n=35, p
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.974