Subtype-associated clinicopathological and tumor immune microenvironment heterogeneity in primary EGFR T790M compound-mutant lung adenocarcinoma: a retrospective cohort study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Primary epidermal growth factor receptor (EGFR) T790M-mutant lung adenocarcinoma (LUAD) is rare, and the clinicopathological characteristics and tumor immune microenvironment (TIME) of different compound-mutant subtypes remain poorly characterized. Methods: We retrospectively analyzed 255 patients with surgically resected primary EGFR T790M compound-mutant LUAD. Tissue microarrays from 158 patients were evaluated using immunohistochemistry (IHC) and multiplex immunofluorescence (mIF). Disease-free survival (DFS) was analyzed using the Kaplan-Meier method, while prognostic factors were evaluated using Cox proportional hazards regression for clinicopathological variables and Firth’s penalized Cox regression for immune markers. Results: Primary EGFR T790M mutation predominantly occurred in compound-mutant form, with T790M+L858R being the most common subtype. Compared with T790M+L858R, T790M+19del had a larger maximum tumor diameter and higher frequencies of lymphovascular invasion, pleural invasion, and lymph node metastasis (all P<0.05). IHC and mIF analyses demonstrated subtype-associated TIME differences. The T790M+19del subtype showed an increased proportion of CD68 + CD163 + macrophages and higher expression of immune-regulatory markers, whereas the T790M+L858R subtype showed relative enrichment of CD3 + CD8 + T cells. In exploratory survival analyses, subtype-specific associations between TIME-related markers and DFS were observed: concurrent high expression of CD66b and CTLA4 was associated with shorter DFS in the T790M+19del subtype, whereas high TIGIT expression was associated with shorter DFS in the T790M+L858R subtype. Conclusions: Primary EGFR T790M compound-mutant LUAD exhibits subtype-associated clinicopathological and TIME heterogeneity. These findings highlight the importance of considering accompanying EGFR activating mutation subtypes when evaluating this rare molecular subgroup.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223960563