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Background  Mutations in the tumor suppressor gene  TP53  and proto-oncogene  PIK3CA  and alterations of p53 and  PIK3CA  AKT mTOR pathways are common events in several human cancers. We focused on the analysis of  TP53  and  PIK3CA  gene variations in adenocarcinoma, squamous cell carcinoma as well as in intraepithelial neoplasia grade 3 of the cervix.    Methods  DNA samples from 28 cervical adenocarcinoma, 55 squamous cell carcinoma and 31 intraepithelial neoplasia grade 3 (CIN3), previously characterized in terms of human papillomavirus (HPV) prevalence and genotype distribution, were analyzed for  TP53  and  PIK3CA  mutations in the exons 4–9 and exon 9, respectively.    Results  Single nucleotide substitutions in  TP53  and  PIK3CA  genes were detected in 36% and 11% of adenocarcinoma, in 16% and in 5% of squamous cell carcinoma, and in 13% and none of CIN 3, respectively. Nucleotide changes in  TP53  were significantly more frequent in adenocarcinoma cases than in squamous cell carcinoma and CIN3 (P = 0.035) and were independent from HPV infection status.    Conclusions  Mutations in the  TP53  gene and to lesser extent in the  PIK3CA  gene seem more frequent in cervical adenocarcinoma than in squamous cell carcinoma and CIN3. Whether  TP53  and  PIK3CA  gene mutations have an impact on prognosis and response to molecularly targeted therapies as well as in cytotoxic drugs in different cervical cancer histotypes needs to be analyzed in investigative clinical trials.

TP53 and PIK3CA gene mutations in adenocarcinoma, squamous cell carcinoma and high-grade intraepithelial neoplasia of the cervix