Expression pattern of p63 and p73 isoforms in cervical carcinoma

Tumor suppressor p53 function is downregulated in most cervical cancers because of its binding to humanpapilloma virus oncoprotein E6 targeting to degradation via ubiquitin proteolysis. Even though, both p63 and p73 share significant homology in structure and function to p53, p63 and p73 encode truncated N-terminal or delta-N isoforms (∆Np63 and ∆Np73) which can inhibit trans-activation of full length isoforms (TAp63 and TAp73). Therefore, overexpression of ∆N isoforms can exert as epigenetic inhibitor of wild type proteins. The aim of this study was to determine whether expression profile of p63 and p73 isoforms are useful markers for predicting tumor progression in cervical cancer. All transcripts were measured using real-time RT-PCR in 66 squamous cell carcinoma (SCCA), 64 cervical dysplasia (31 low grade squamous intra-epithelials lesion; LSIL and 33 high grade squamous intra-epithelials lesion; HSIL) and 31 normal cervix. TAp73 but not TAp63 was significantly up-regulated with respect to the progression from LSIL to HSIL and SCCA whereas, both ∆Np73 and ∆Np63 were up-regulated in SCCA comparing to normal (P < 0.05, Mann-Whitney test). Moreover, ∆Np63 transcripts in SCCA show a significant up-regulation than normal, LSIL, and HSIL with P value = 0.003, < 0.001, and = 0.002, respectively. This data indicated that ∆Np63 rather than ∆Np73 could predict cancer progression from dysplasia to more advance stage. The ratio of isoforms fraction was further evaluated as potential marker to predict cancer progression. Significant P value was earlier obtained at LSIL to HSIL when using the ratio between TAp73 and ∆Np73 isoforms. In conclusion, p73 isoforms ratio is considered as an early potential marker to predict cancer progression from LSIL to HSIL and SCCA.