Early detection of colorectal cancer metastasis and relapse by recognizing nonspecific cross-reacting antigen 2 in commercial carcinoembryonic antigen assays.

Carcinoembryonic antigen (CEA), one of the first known tumor markers, is still the most useful clinical marker to aid in the diagnosis and monitoring of colorectal cancer. Many commercial assays are available for measuring CEA, but their practical use is complicated by the molecular heterogeneity of CEA. CEA is a heavily glycosylated protein of the immunoglobulin gene superfamily and has several related antigens such as nonspecific crossreacting antigen (NCA), NCA-2, and normal fecal antigen. Previous investigations have indicated that some commercial assays for CEA cross-react with various CEA antigens owing to the epitope group specificity of the monoclonal antibodies (mAbs) employed in the assay (1, 2). NCA-2 is a member of the CEA gene family and is structurally most similar to CEA. It has been reported that CEA might be increased in the serum of some colorectal cancer patients, and the cross-reactivity to NCA-2 might be a beneficial characteristic of CEA assays with respect to their diagnostic sensitivity in colorectal cancer patients (3). A patient who had colorectal cancer and underwent a transverse colectomy at our hospital in 1996 suffered relapses of the cancer in 2000, 2002, and 2003 and had chemotherapy and surgical resection each time. In 2006, metastasis was detected in the liver, and surgery was performed to resect the liver metas-