High-Precision Quantitative Analysis Reveals Carcinoembryonic Protein Expression Differs Among Colorectal Cancer Primary Foci and Metastases to Different Sites

Abstract

The expression of carcinoembryonic protein (CEA) is an important biological marker and therapeutic target in colorectal cancer (CRC). CEA expression heterogeneity confers resistance to CEA-targeting immunotherapy antibodies. Thus, quantification of the CEA-positive cell ratio among all tumor cells would be important in identifying patients that would benefit from CEA-targeted therapies. However, the proportion of tumor cells that express CEA within primary and metastasized tumors at different sites has not been studied. Therefore, the present study aimed to determine CEA positive cell proportion in paired CRC primary foci, liver metastases, and lymph node (LN) metastases, and whether proportion of CEA positive cell differs among colorectal cancer primary foci, liver metastases, and LN metastases from 26 patients. The CEA expression was detected by immunohistochemical assay. Then we set up a quantification approach to quantify the proportion of CEA-positive cells based on the TissueGnostics (TG) system. Then the proportion of CEA positive cells were measured and compared among primary foci, liver metastases, and LN metastases. As a result, the proportion of CEA positive tumor cells was slightly higher in liver metastases than in primary foci (89.8% ± 2.71% vs 82.1% ± 5.05%, P < 0.001). The proportion of CEA-positive cells was significantly lower in LN metastases than in primary foci (82.3% ± 4.32% vs 70.28% ± 5.04%, P < 0.001). In 8 cases with matched CRC primary foci, liver metastases, and LN metastases, the proportions of CEA proportion in liver metastasis was the highest, followed by primary foci and LNs metastasis. In conclusion, this study provided an new approach for quantification of CEA positive cell in tumors and proved the percentage of CEA-positive cells varied in different metastases.