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Expression of Np73 and TAp73 Independently Associated with Radiosensitivities and Prognoses in Cervical Squamous Cell Carcinoma

Authors' Affiliations: Departments of ¹ Obstetrics and Gynaecology and ² Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China

Requests for reprints: Hextan Yuen-Sheung Ngan, Department of Obstetrics and Gynaecology, Queen Mary Hospital, 6th floor, Professorial Block, Pokfulam Road, Hong Kong, China. Phone: 852-28554684; Fax: 852-28550947; E-mail: hysngan{at}hkucc.hku.hk.

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 (Np73 and TAp73) 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 Np73 and TAp73 in 117 cervical SCC and 113 normal cervical tissues using immunohistochemistry. The expression levels were analyzed with clinical variables and patients' survival.

Results: Np73and TAp73 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 Np73 was significantly found in SCC resistant to irradiation (P < 0.001), whereas increase of TAp73 expression was observed in the majority of SCC sensitive to irradiation (P < 0.001). Multivariate and survival analyses indicated that the expressions of Np73 and TAp73 were independently associated with prognosis: Np73 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 TAp73 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 (Np73 and TAp73) might be potential markers for predicting the prognosis and sensitivity to radiotherapy in patients with cervical SCC.

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