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Early studies show CEACAM5 is highly expressed in ~25% of advanced NSq NSCLC patients.^2,3

High expression is defined as expression at ≥2+ intensity in ≥50% of tumor cells as visualized by immunohistochemistry.^2,4

Higher CEACAM5 expression is detected in tumor tissues compared with that in normal tissues in patients with NSCLC, indicating the critical role of CEACAM5 in the pathogenesis of NSCLC.⁵ Specifically in advanced NSq NSCLC, CEACAM5 may play a potential role in tumor progression, metastasis, and cell adhesion.^1,4,5 CEACAM5 expression is also potentially associated with cell proliferation and migration.⁵

CEACAM5 has been shown to have higher expression in advanced NSq NSCLC and lower expression in normal lung tissue.^4,5 When looking at protein expression, CEACAM5 is highly expressed in tumor tissues, but it is virtually undetectable in normal lung tissue.⁴ High differential expression in lung cancer cells may ultimately allow CEACAM5 to become a potential target in NSCLC.^4,6 High CEACAM5 expression is also potentially associated with tumor progression in NSCLC by promoting cell proliferation and migration.⁵ CEACAM5 cell-surface glycoproteins may play a potential role in tumor progression, metastasis, and cell adhesion — inhibiting differentiation and apoptosis while disrupting tissue architecture.^1,5,6

CEA was first discovered as a tumor marker for colorectal cancer. This discovery led to the further identification of other CEA-related proteins, later unified under the name CEACAM, with the original CEA protein being renamed CEACAM5.¹ The commercially available assays for detecting CEA can detect more than one member of the CEA family.^7,8

CEACAM5 is a member of the CEACAM family of 12 glycoproteins and is believed to help drive cell adhesion and migration, as well as, when overexpressed, inhibit apoptosis.^1,5,6 Under normal physiologic conditions, there are low levels of tissue CEACAM5. However, CEACAM5 is upregulated in many different cancers.^5,9

Biomarkers for approved therapy in NSCLC include: PD-L1, with an expression rate of 63%; EGFR [North America and Western Europe] (9%-13%); ALK (4%-5%); ROS1 (2%); BRAF (1%-5%); HER2 mutation (1%-4%); NTRK1/2/3 (0.1%); MET mutation (3%-4%); RET (1%-2%); KRAS-G12C (13%); and cMET (25%).^10-20

While there are currently no treatments targeting CEACAM5 in NSCLC, CEACAM5 expression is measured via IHC, which is also generally used to test for PD-L1.^4,21

The IHC tissue testing requirements for CEACAM5 are similar to tissue testing requirements for PD-L1.^4,21

At this time, liquid-based tests including serum CEA cannot be used instead of tissue CEACAM5 IHC test. It has not been definitively established if CEA serum testing that report levels of circulating CEA protein in blood correlate with IHC quantification in patients with advanced NSq NSCLC. The research on this topic is ongoing currently.^4,7

CEACAM5 expression can be quantified by using immunohistochemistry (IHC). CEACAM5 expression is not associated with CEACAM genetic alterations; hence DNA-based NGS cannot be used. It has not been definitively established if CEACAM5 RNA gene expression detected by NGS correlates with IHC quantification in patients with advanced NSq NSCLC.^4,22