144P - Correlation of EZH2 expression and response to chemoradiotherapy 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. Therefore, there is an urgent need to identify molecular markers that can predict recurrence and treatment response. Enhancer of zeste homolog 2 (EZH2), an epigenetic modifier, plays a role in cancer development by promoting the 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

50 patients were prospectively included in this study. All of the patients received definitive CRT. A second biopsy was retrieved between the 3^rd and 4^th fraction of radiotherapy (RT). Immunohistochemistry was performed on both pre-RT and post-3rd 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 four or more indicated high expression. After 12 weeks, treatment response was assessed and correlated with EZH2 status. The statistical analysis was done using IBM SPSS version 26, considering p-values less than 0.05 as statistically significant.

Results

The EZH2 score was significantly higher in tumor tissue than in normal mucosa samples (p=0.001). High expression of EZH2 was found in 78% of pre-RT and 81% of post-3rd fraction samples. High expression of EZH2 did not show a statistically significant correlation with response to CRT (p=0.80). However, the EZH2 score increased significantly in the post-3rd fraction samples of patients who did not achieve a complete response (p=0.03). The subgroup analysis revealed a statistically significant correlation between the high expression of EZH2 and a lack of response (complete response + partial response) to treatment in patients with oral cavity cancers (p=0.015).

Conclusions

The study indicates that EZH2 can be a valuable predictive marker in HNC, but further research with a larger cohort is needed. Anti-EZH2 therapy should be explored to improve treatment outcomes in patients with high expression of EZH2.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.