Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers.
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.


CONCLUSIONS
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.
Blumenthal
Rosalyn D
RD
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA. Rblumenthal@gscancer.org <Rblumenthal@gscancer.org>
Leon
Evelyn
E
Hansen
Hans J
HJ
Goldenberg
David M
DM
D015703:Antigens, CD / Q000235:genetics*; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000401:mortality; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D016019:Survival Analysis
D015703:Antigens, CD; C504117:CEACAM6 protein, human; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins