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 (deltaNp73 and TAp73alpha) 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 deltaNp73 and TAp73alpha in 117 cervical SCC and 113 normal cervical tissues using immunohistochemistry. The expression levels were analyzed with clinical variables and patients' survival. RESULTS: DeltaNp73and TAp73alpha 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 deltaNp73 was significantly found in SCC resistant to irradiation (P < 0.001), whereas increase of TAp73alpha expression was observed in the majority of SCC sensitive to irradiation (P < 0.001). Multivariate and survival analyses indicated that the expressions of deltaNp73 and TAp73alpha were independently associated with prognosis: deltaNp73 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 TAp73alpha 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 (deltaNp73 and TAp73alpha) might be potential markers for predicting the prognosis and sensitivity to radiotherapy in patients with cervical SCC.
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 (deltaNp73 and TAp73alpha) in cervical squamous cell carcinomas (SCC) and the relationship between their expressions and prognostic significance in cervical SCCpatients. EXPERIMENTAL DESIGN: We investigated the protein expressions of deltaNp73 and TAp73alpha in 117 cervical SCC and 113 normal cervical tissues using immunohistochemistry. The expression levels were analyzed with clinical variables and patients' survival. RESULTS: DeltaNp73and TAp73alpha 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 deltaNp73 was significantly found in SCC resistant to irradiation (P < 0.001), whereas increase of TAp73alpha expression was observed in the majority of SCC sensitive to irradiation (P < 0.001). Multivariate and survival analyses indicated that the expressions of deltaNp73 and TAp73alpha were independently associated with prognosis: deltaNp73 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 TAp73alpha predicted a better survival of cervical SCCpatients (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 (deltaNp73 and TAp73alpha) might be potential markers for predicting the prognosis and sensitivity to radiotherapy in patients with cervical SCC.
Authors: Margareta T Wilhelm; Alessandro Rufini; Monica K Wetzel; Katsuya Tsuchihara; Satoshi Inoue; Richard Tomasini; Annick Itie-Youten; Andrew Wakeham; Marie Arsenian-Henriksson; Gerry Melino; David R Kaplan; Freda D Miller; Tak W Mak Journal: Genes Dev Date: 2010-03-01 Impact factor: 11.361