Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers

Abstract

Background: Many breast, pancreatic, colonic and non-small-cell lung carcinoma lines express CEACAM6 (NCA-90) and CEACAM5 (carcinoembryonic antigen, CEA), and antibodies to both can affect tumor cell growth in vitro and in vivo. Here, we compare both antigens as a function of histological phenotype in breast, pancreatic, lung, ovarian, and prostatic cancers, including patient-matched normal, primary tumor, and metastatic breast and colonic cancer specimens.

Methods: Antigen expression was determined by immunohistochemistry (IHC) using tissue microarrays with MN-15 and MN-3 antibodies targeting the A1B1- and N-domains of CEACAM6, respectively, and the MN-14 antibody targeting the A3B3 domain of CEACAM5. IHC was performed using avidin-biotin-diaminobenzide staining. The average score +/- SD (0 = negative/8 = highest) for each histotype was recorded.

Results: For all tumors, the amount of CEACAM6 expressed was greater than that of CEACAM5, and reflected tumor histotype. In breast tumors, CEACAM6 was highest in papillary > infiltrating ductal > lobular > phyllodes; in pancreatic tumors, moderately-differentiated > well-differentiated > poorly-differentiated tumors; mucinous ovarian adenocarcinomas had almost 3-fold more CEACAM6 than serous ovarian adenocarcinomas; lung adenocarcinomas > squamous tumors; and liver metastases of colonic carcinoma > primary tumors = lymph nodes metastases > normal intestine. However, CEACAM6 expression was similar in prostate cancer and normal tissues. The amount of CEACAM6 in metastatic colon tumors found in liver was higher than in many primary colon tumors. In contrast, CEACAM6 immunostaining of lymph node metastases from breast, colon, or lung tumors was similar to the primary tumor.

Conclusion: CEACAM6 expression is elevated in many solid tumors, but variable as a function of histotype. Based on previous work demonstrating a role for CEACAM6 in tumor cell migration, invasion and adhesion, and formation of distant metastases (Blumenthal et al., Cancer Res 65: 8809-8817, 2005), it may be a promising target for antibody-based therapy.

Figure 1

CEACAM5 and CEACAM6 staining of colon, ovarian, breast, lung, prostate and pancreatic tissue core specimens as a function of tumor histotype is summarized. The results graphed represent the mean ± standard deviation for each histotype and antigen.

Figure 2

CEACAM5 and CEACAM6 expression in representative cases of infiltrating ductal, papillary, lobular and phyllodes breast tumor cores.

Figure 3

CEACAM5 and CEACAM6 expression in representative cases of well-, moderately-, poorly differentiated adenocarcinoma, squamous carcinoma of lung, brochioalveolar, large-cell neuroendocrine, large-cell, and small-cell lung carcinoma cores.

Figure 4

CEACAM5 and CEACAM6 expression in representative cases of well-, moderately-well-, moderately-, moderately-poorly, and poorly-differentiated adenocarcinoma and non-neoplastic pancreatic tissue cores.

Figure 5

CEACAM5 and CEACAM6 expression in representative stage II, stage III, and stage IV prostate cancer cases with non-neoplastic prostate tissues.

Figure 6

CEACAM5 and CEACAM6 expression in representative non-neoplastic and adenocarcinoma cases of the colon.

Figure 7

CEACAM5 and CEACAM6 expression in representative cases of serous and mucinous adenocarcinoma, endometroid, yolk sac, and transitional cell carcinoma of the ovary.

Figure 8

Immunohistochemical staining of four matched patient specimens from normal colon, primary colon carcinoma, and liver metastasis stained with MN-15 anti-CEACAM6.