Objective: Mutations of the tumor suppressor gene TP53 are the most significant events in several human cancers. Few studies have analyzed the frequency of TP53 alterations in squamous cell carcinoma and adenocarcinoma of the cervix with controversial results. This study provides a detailed analysis of TP53 mutation spectra in cervical squamous cell carcinoma and adenocarcinoma from different geographical regions.
Methods: The analysis of TP53 mutational profiles was performed in 1353 cervical cancers retrieved from the IARC p53 mutation database (R15, 2010) and the COSMIC data along with the literature review of related studies identified by PubMed searching.
Results: This analysis showed a significant higher mutation frequency of TP53 gene in cervical adenocarcinoma (32 of 241; 13.3%) compared to squamous cell carcinoma (39 of 657; 5.9%; P=0.0003, χ(2) test). The proportion of adenocarcinoma with mutated TP53 varied from 4% in North America to 19% in Asia. Among the six hot-spot codons of TP53 gene, three codons (175, 248 and 273) were the most commonly mutated in both types of cervical cancer, one codon (249) mainly in squamous cell carcinoma and one codon (282) only in adenocarcinoma. The G to A and C to T transitions were the prevalent type of mutations in both squamous cell carcinoma and adenocarcinoma (48.7% and 53.5% of all mutations, respectively). The frequency of C to A transversion was relatively high only in adenocarcinoma (25%), while the mirror mutation G to T was comparatively frequent in squamous cell carcinoma (14.6%).
Conclusions: Different patterns of TP53 mutations occur in squamous cell carcinoma and adenocarcinoma of the cervix in different regions of the world. The highest frequency of mutated TP53 has been observed in cervical adenocarcinoma from Asia. Further studies are needed to better define the role of TP53 alterations in cervical cancer and possibly to understand the impact of mutations on cancer prognosis and outcomes.
Copyright © 2012 Elsevier Inc. All rights reserved.