Correlation of EZH2 expression and response to chemoradiation in patients with locally advanced inoperable oral cavity and oropharyngeal squamous cell cancers.

BACKGROUND: Head and neck cancer (HNC) is a major global health concern. Despite advances in treatment, the outcome is poor due to locoregional failure. Enhancer of zeste homolog 2 (EZH2), an epigenetic modifier, plays a role in cancer development by promoting growth, invasion, and dissemination of tumor cells. This study aims to investigate the correlation between EZH2 expression and the response to chemoradiation (CRT) in patients with locally advanced, inoperable oral cavity and oropharyngeal squamous cell cancers.

METHODS: Fifty patients were prospectively included in this study. All of the patients received definitive CRT. A second biopsy was retrieved between the third and fourth fractions of radiotherapy (RT). Immunohistochemistry (IHC) was performed on pre-RT and postthird fraction biopsy samples to evaluate EZH2 status. The IHC score was calculated based on EZH2 intensity and the percentage of positive cells. A score of 4 or more indicated high expression. After 12 weeks of treatment completion, the response was assessed and correlated with EZH2 status, and the statistical analysis was done.

RESULTS: The EZH2 score was significantly higher in tumor tissue than in normal tissue samples (P value: 0.001). High expression of EZH2 was found in 78% of pre-RT and 81% of postthird fraction tumor samples. High expression of EZH2 did not show a statistically significant correlation with response to CRT (P value: 0.809). However, the EZH2 score increased significantly in the postthird fraction samples of patients who did not achieve a complete response (P value: 0.03).

CONCLUSION: The study indicates that EZH2 can be a valuable predictive marker in HNC. Anti-EZH2 therapy should be explored to improve the treatment outcomes in patients with high expression of EZH2.