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The Landscape of CEACAM5 Expression by Immunohistochemistry in NSCLC
Ying-Han R Hsu1,2, Amna Almutrafi1,3, Katrina Hueniken1
1University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
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.
Insights
High CEACAM5 expression occurs in 18% of non-small cell lung cancer (NSCLC) patients. CEACAM5 protein levels did not correlate with prognosis or common mutations in NSCLC.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Biomarkers
Background:
- Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a therapeutic target in non-small cell lung cancer (NSCLC).
- Previous studies suggest CEACAM5 is highly expressed in about 25% of lung adenocarcinoma cases.
- Limited real-world data exists on CEACAM5 expression prevalence and prognostic significance in NSCLC.
Purpose of the Study:
- To systematically evaluate CEACAM5 protein expression in a large, real-world NSCLC patient population.
- To assess the correlation of CEACAM5 expression with clinical parameters, including PD-L1 status and driver mutations.
- To determine the prognostic impact of CEACAM5 protein expression on patient survival.
Main Methods:
- CEACAM5 protein expression was assessed via immunohistochemistry in two NSCLC cohorts using clinical biopsy and resection specimens.
- Expression was scored by three pathologists as high (≥50% tumor cells, ≥2+ intensity), moderate (1-49% tumor cells, ≥2+ intensity), or negative (0/1+ intensity).
- Statistical analyses included interrater reliability assessment, Fisher's exact test, chi-square test, and log-rank tests for survival correlation.
Main Results:
- Moderate interrater reliability was observed among pathologists for CEACAM5 assessment.
- High CEACAM5 expression was found in 18% of the NSCLC patient cohort.
- No significant correlation was found between CEACAM5 expression and tumor stage, PD-L1 expression, tumor mutation burden, or EGFR/KRAS mutations.
Conclusions:
- Approximately 18% of NSCLC cases exhibit high CEACAM5 expression based on immunohistochemistry.
- CEACAM5 expression levels in NSCLC did not demonstrate a significant association with oncogenic driver mutations.
- CEACAM5 protein expression showed no prognostic value for recurrence-free or overall survival in this NSCLC cohort.
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