Exploring spatial heterogeneity of PD-L1 and c-MET expression in oral squamous cell carcinoma

Abstract Background PD-L1 expression is an established predictive biomarker for immune checkpoint inhibitor therapy in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC). However, the spatial heterogeneity of PD-L1 and additional biomarkers such as c-MET between primary tumors and lymph node metastases remains insufficiently characterized. Given the potential for compartment-specific biomarker differences between primary tumors and metastatic lesions, we investigated PD-L1 and c-MET expression patterns in matched primary tumors and lymph node metastases of OSCC patients. Methods In this retrospective cohort study, PD-L1 expression (Tumor Proportion Score [TPS], Combined Positive Score [CPS]) and c-MET expression (H-score, percentage-based scoring) were analyzed by immunohistochemistry in primary tumors from 59 OSCC patients. Matched primary tumor–lymph node metastasis pairs were available for 24 patients and served as the basis for the paired spatial heterogeneity analyses. Biomarker concordance between primary tumors and metastases as well as associations with clinicopathologic parameters were evaluated. Results Both PD-L1 and c-MET were frequently expressed in primary tumors but showed significantly lower expression levels in matched lymph node metastases. Higher PD-L1 expression in primary tumors was associated with nodal metastasis in exploratory analyses, whereas c-MET expression showed no significant association with nodal status. No significant correlation between PD-L1 and c-MET expression was observed. Furthermore, discordance of PD-L1 CPS status between primary tumors and lymph node metastases resulted in different biomarker classifications in a substantial subset of matched cases. In exploratory analyses, biomarker expression and primary tumor–lymph node discordance were not significantly associated with recurrence, although the limited number of events precludes definitive conclusions. Conclusions Our findings demonstrate pronounced spatial heterogeneity of PD-L1 and c-MET expression in OSCC and reveal compartment-specific biomarker expression patterns between primary tumors and lymph node metastases. The observed discordance between tumor compartments warrants further investigation in larger prospective studies to determine its biological and potential clinical relevance for biomarker assessment in OSCC.