EGFR and MET Protein Expression in Brain Metastases of EGFR-Mutated Lung Adenocarcinoma: Prognostic Impact and Comparison with Primary Tumors

Patients with EGFR -mutated lung adenocarcinoma (LUAD) frequently develop brain metastases (BrMs), representing a major clinical challenge. The EGFR-MET bispecific antibody amivantamab shows promise in patients with stable BrMs, but the biological basis for its intracranial activity remains poorly understood. We aimed to characterize EGFR and MET protein expression in resected BrMs and evaluate their prognostic and therapeutic implications. We retrospectively analyzed 21 patients with EGFR -mutated LUAD who underwent surgical resection of BrMs. A subgroup of 9 patients had paired primary tumors for comparative analysis. EGFR and MET protein expression were assessed by immunohistochemistry using H-scores. In the full cohort (N = 21), High EGFR expression in BrMs was associated with significantly shorter overall survival (OS) (median, 28.6 vs 83.0 months; p=0.048). MET expression was not prognostic. In the paired analysis (N=9), BrMs showed significantly higher EGFR expression than primary tumors (p = 0.014), while MET expression showed a similar, nonsignificant trend (p = 0.098). In this hypothesis-generating study with a limited sample size, high EGFR expression in resected BrMs of EGFR-mutated LUAD patients was associated with poor prognosis, possibly representing a clinically distinct subset. BrMs exhibited significantly higher EGFR expression than primary tumors, with a similar trend for MET. These findings highlight distinct molecular features of BrMs and provide a rationale for investigating EGFR- and MET-targeted therapies, such as amivantamab, in patients with active BrMs from EGFR -mutated LUAD.