Overexpression of p63 is associated with radiation resistance and prognosis in oral squamous cell carcinoma

Summary 

Background: The tumor suppressor homologue p63 is expressed in basal and parabasal layers of intraoral mucosa. Full length transcripts with transactivational domain (TA forms) present with homology to p53 and implicate functions governing cell proliferation, differentiation and apoptosis control. To date studies show an increase of p63 expression in oral dysplasia and additionally high expression levels correlated with poor prognosis for patients with OSCC, whereas a possible link to radiation resistance of tumors has not been investigated yet. In the present study we tested the hypothesis for p63 being a marker of radioresistance and overall survival in OSCC. Methods: p63 Expression was labeled by immunohistochemistry in pre-treatment biopsies collected from 33 patients with OSCC. Quantification of the labeling index (Li) based on the relation of p63 positive cells to overall tumor cell count. Histological examination of the resection specimen allowed categorization of the radiation response. Statistical analyses of the association between Li and radiation response were performed. Survival analysis utilized Kaplan–Meier estimates and additionally a Cox regression model was built for p63 (Li), T stage, N-stage and chemotherapy and presented as hazard ratios. Results: All tumors had enhanced p63 expression. The median Li was 63.1% (range 36–87%). Tumors with a p63 positive cell count>63.1% showed increased resistance to radiation (p=0.027). Overall survival was higher (p=0.001) for patients with low Li (<median value) than those with high Li (>median value) and multivariate Cox regression analysis confirmed the significance of p63 as a prognostic marker of survival. Conclusions: The results of this analysis advocate p63 expression in pre-treatment tumor tissue to be a marker of radiation resistance in OSCC, with high expression levels being associated with poor radiation response and shorter survival. The promising results of this biomarker should now be confirmed by a study with larger patient counts.

Keywords: p63, Head and neck cancer, Radiation, Radiation resistance, Oral cancer

Abbreviations: p63, protein 63, CAI-X, carboanhydrase X, Li, labeling index, DÖSAK, deutsch österreichisch schweizerischer Arbeitskreis für Tumoren im Kiefer- und Gesichtsbereich, OSSC, oral squamous cell carcinoma, H&NSSC, squamous cell carcinoma of the head and neck, PBS, phosphate buffered saline, CR, complete response, GPR, good partial response, MPR, minor partial response