XPA – A biomarker with potential prognostic value in patients with oropharyngeal head and neck squamous cell carcinoma

Purpose: Platinum based chemotherapy resistance has been under investigation for a long time looking at the nucleotide excision repair (NER) pathway that is responsible for DNA adduct repair. One of the participating proteins in that pathway is XPA. There is little information about this protein regarding prognostic value in patients with head and neck squamous cell carcinoma (HNSCC). Therefore, we investigated XPA expression as a prognostic factor by retrospectively looking at overall survival, time to recurrence and correlation with clinical parameters. Material and Methods: Tissue microarrays were constructed from 453 cases of HNSCC including 222 oral (49%), 126 pharyngeal (27.8%) and 105 laryngeal (23.2%) tumors. 293tumor blocks were evaluable for XPA immunohistochemistry. Expression levels were dichotomized into a high and low XPA expressing group followed by a comparison of age, gender, TNM status, Grading and UICC stage. Outcomes for overall survival and time to recurrence were analyzed by using the Kaplan-Meier method and performed for different subsites of the head and neck. Results: Analysis of overall survival and time to recurrence showed no difference between both expression levels of XPA in the overall patient cohort. But superior overall survival in patients with oropharyngeal SCC and a high XPA expression could be observed (p=0.0386). Looking at SCCs of the oral cavity a slight trend towards an inferior overall survival in patients with a high XPA expression could be shown. Whereas investigations in the hypopharynx and larynx showed no significant differences between high and low XPA expressing tumors. Looking generally at gender, M stage and grading no statistical correlation was found. Analyzing T and N stage in all tumors a trend towards a lower XPA expression in advanced tumors (>pT4 p=0.0543 and >pN1 p=0.0546) could be seen. This trend was confirmed by statistically lower expression of XPA in all patients with UICC stage IV (p=0.035) and could also be shown in SCC of the oral cavity but not in other subsites. Conclusions: The shown results suggest that XPA might be a novel predictive marker for overall survival in patients with oropharyngeal squamous cell carcinoma with a superior survival in tumors with high XPA expression. Further, this study shows that subsites in the head and neck will have to be looked at separately in the future to determine the predictive value of biomarkers for therapy outcome and pretherapeutic risk stratification of patients. To increase statistical power of this study and to evaluate the effect on platinum based chemotherapy resistance further studies are ongoing at the moment.