Expression of ΔNp73 and TAp73α independently associated with radiosensitivities and prognoses in cervical squamous cell carcinoma

Abstract

Purpose: The p73 gene produces different protein isoforms using alternative promoters and splicing, which have different biological characteristics. This study was to investigate the expression patterns of two distinct p73 isoforms (σNp73 and TAp73Δ) in cervical squamous cell carcinomas (SCC) and the relationship between their expressions and prognostic significance in cervical SCC patients. Experimental Design: We investigated the protein expressions of ΔNp73 and TAp73α in 117 cervical SCC and 113 normal cervical tissues using immunohistochemistry. The expression levels were analyzed with clinical variables and patients' survival. Results: ΔNp73 and TAp73α were significantly overexpressed in cervical SCC compared with those in normal cervical epithelium (P < 0.001). However, their expressions were inversely correlated (P < 0.001, R = -0.368) and associated with differential tumor radiosensitivity. Overexpression of ΔNP73 was significantly found in SCC resistant to irradiation (P < 0.001), whereas increase of TAp73α expression was observed in the majority of SCC sensitive to irradiation (P < 0.001). Multivariate and survival analyses indicated that the expressions of ΔNp73 and TAp73α were independently associated with prognosis: ΔNp73 was associated with recurrence of the disease [P = 0.001; odds ratio (OR), 4.857] and an adverse outcome (P = 0.012; OR, 4.676), whereas TAp73α predicted a better survival of cervical SCC patients (P = 0.018; OR, 0.065). Conclusions: The p73 gene might be an important determinant of cellular response to irradiation. The expressions of the two main isoforms (ΔNp73 and TAp73α) might be potential markers for predicting the prognosis and sensitivity to radiotherapy in patients with cervical SCC. © 2006 American Association for Cancer Research.