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CEACAM5 as a biomarker of semi-solid, lepidic lung adenocarcinoma
Journal article   Open access   Peer reviewed

CEACAM5 as a biomarker of semi-solid, lepidic lung adenocarcinoma

Justin M. Bader, William de Santis, Emma Kane, Anjali Jaiswal, Christina Cho, Michal Kidacki, Lieping Chen, Sanja Dacic and Gavitt A. Woodard
Translational lung cancer research, Vol.15(5), 131
05/31/2026
DOI: 10.21037/tlcr-2026-1-0102
PMCID: PMC13263804
PMID: 42291360
url
https://doi.org/10.21037/tlcr-2026-1-0102View
Published (Version of record) Open Access

Abstract

Background: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a cell adhesion molecule implicated in tumor cell migration, invasion, and resistance to apoptosis. Its role as a circulating biomarker in the form of carcinoembryonic antigen (CEA) is well-established in gastrointestinal malignancies. CEACAM5 is also overexpressed in approximately 25% of non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma, yet its role as a biomarker and therapeutic target remains unclear. We previously demonstrated elevated CEACAM5 RNA expression in lepidic adenocarcinomas that appear radiographically as ground-glass opacities (GGOs) and semi-solid lung cancer. In this study, using a separate patient cohort, we assess CEACAM5 protein expression as a potential biomarker in GGO and semi-solid NSCLC. Methods: CEACAM5 immunohistochemistry (IHC) was performed in a Clinical Laboratory Improvement Amendments (CLIA) certified setting on surgically resected NSCLC. Slides underwent expert thoracic pathologist review and quantification of CEACAM5 expression with standardized H-score. Expression was compared between tumors which were radiographically subsolid, ground-glass, with pathologic lepidic adenocarcinoma (GGO) (n=36) versus solid NSCLC tumors (n=98), and sub-group comparisons were performed based on patient and tumor characteristics. Specimens underwent multiplex immunofluorescence to characterize the immune microenvironment and quantify CD8+ T cell and CD20+ B cell infiltration. Results: Lepidic adenocarcinoma GGOs exhibited higher CEACAM5 expression than solid NSCLC (H-score: 53 vs. 27, P<0.001). This increase was also observed when compared to individual NSCLC subtypes including lung adenocarcinoma (n=57, H-score: 53 vs. 35, P=0.009), squamous cell carcinoma (n=20, H-score: 53 vs. 4.6, P=0.003), and large cell carcinoma (n=10, H-score: 53 vs. 12, P=0.02). Among the GGO cohort, specimens with CEACAM5 H-score 100 exhibited a higher density of PanCK+ tumor cells (5.5% vs. 2.2%, P=0.02). Among the adenocarcinoma cohort, patients with higher stage adenocarcinoma (stage II–IV) had higher CEACAM5 H-scores than patients with stage I adenocarcinoma although not statistically significant (H-score: 50 vs. 28, P=0.09). The GGO specimens with the highest CEACAM5 H-scores (≥100, n=5) had a clinical history of radiographic evolution, and developing a new radiographic solid component prior to surgical resection, compared to GGO with lower CEACAM5 H-scores (<100, n=6) where this radiographic evolution was observed in only 46%. Conclusions: Our findings demonstrate that CEACAM5 is significantly overexpressed in lepidic adenocarcinoma GGO compared to other forms of solid NSCLC, suggesting its potential utility as a diagnostic biomarker for this subtype of NSCLC. Future studies should explore the clinical utility of CEACAM5-targeted strategies for early detection of invasive lung cancer and lung nodule risk stratification.
 Biomarkers Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) lung adenocarcinoma precision medicine semi-solid nodules

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