The Landscape of CEACAM5 Expression by Immunohistochemistry in NSCLC.

Introduction: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a target of antibody-drug conjugate therapy for NSCLC. High expression of CEACAM5 has been reported in approximately 25% of patients with lung adenocarcinoma. However, CEACAM5 expression has not been systematically examined in a real-world and large patient population with NSCLC. There are also limited data on the prognostic impact of CEACAM5 protein expression. Methods: We assessed CEACAM5 protein expression by immunohistochemistry in two separate cohorts of patients with NSCLC to include both routine clinical biopsy and resection specimens, using the anti-CEACAM5 clone 769 antibody assay protocol and scoring scheme for the tusamitamab ravtansine clinical trials. Expression levels were categorized as high (≥50% tumor cells at ≥2+ intensity), moderate (1%-49% tumor cells at ≥2+ intensity), and negative (0/1+ intensity) and scored independently by three thoracic pathologists. Interrater reliability was determined by Kendall's coefficient of concordance and Fleiss' kappa. Association with PD-L1 and driver mutation was calculated by Fisher exact or chi-square test. Correlation with recurrence-free survival and overall survival was determined by log-rank tests. Results: The interrater reliability of CEACAM5 assessment was moderate among three pathologists. The overall prevalence of high CEACAM5 expression was 18%. CEACAM5 expression did not significantly correlate with tumor stage, PD-L1 expression, tumor mutation burden, and EGFR or KRAS mutations. There was no prognostic effect of CEACAM5 expression on recurrence-free survival or overall survival. Conclusions: Our data revealed that 18% of routinely diagnosed clinical NSCLC samples had high CEACAM5 expression by immunohistochemistry, and its expression was not associated with oncogenic driver mutations or patient prognosis in a predominantly early stage NSCLC cohort.