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Markers in breast cancer

Carcinoembryonic antigen
(CEA)



Other name(s)

CD66e


Molecular biology

Gene: the CEA gene family, consisting of approximately 10 genes, is contained in a region located at 19q13.1-q13.2. The CEA gene subgroup has 9 members, including CEA, nonspecific crossreacting antigen (NCA), biliary glycoprotein (BGP1), and 6 genes referred to as CEA gene family members: CGM1, CGM2, CGM6, CGM7, CGM8, and CGM9 .
mRNA: at least 4 CEA mRNAs have been described, with sizes of 3.5, 3.0, 2.6, 2.3 kb, respectively (Cournoyer D. et al., 1988)
Protein: a complex immunoreactive 180-kDa glycoprotein comprising 60% carbohydrate. CEA immunoassay is useful in the diagnosis and serial monitoring of cancer patients for recurrent disease or response to therapy. CEA is synthesized as a precursor with a signal peptide followed by 668 amino acids of the mature CEA peptide.


Breast cancer

Cell lines:

Tumors:
- It has been suggested that RT-PCR detection of CEA mRNA in the lymph nodes or the peripheral blood could be potentially very useful to determine high-risk patients for metastasis (Mori M. et al., 1998). However, other studies showed that CEA mRNA was also expressed in the blood and lymph nodes of patients without cancer (Bostick P.J. et al., 1998). By RT-PCR, CEA was found in 5 of 19 bone marrow samples from healthy individuals, demonstrating the lack of specificity of this marker for the detection of micrometastases (Zippelius A. et al., 1997).

- In 550 patients with breast cancer without known metastases the levels of the serum tumour markers CEA und CA 15-3 were determined preoperatively and during follow-up. The prognostic relevance of these markers for recurrence (n = 128/487) and death of disease (n = 55/550) was evaluated in relation to established prognostic factors. In univariate analysis tumour size, lymph nodes, histological grading, age, hormone receptors, preoperative value of CEA (cut-off 2 ng/mL) and CA 15-3 (cut-off 25 U/mL) and their decrease of more than 33% within seven months after operation were significant for relapse. The results for death of disease were similar except for age. In multivariate analysis tumour size, lymph nodes and decrease of CEA > 33% were independent prognostic factors for recurrence. For overall survival tumour size, lymph nodes, histological grading and preoperative levels of CEA > or = 2 ng/mL and of CA 15-3 > or = 25 U/mL were independent prognostic factors (Ebeling F.C. et al., 1999).

- In 1228 serum samples of 664 women with history of breast cancer, the diagnostic accuracy and predictive power of CEA and CA 15-3 for the detection of disease relapse was determined prospectively by analyzing the clinical course for at least 6 months after the measurement of the tumor markers. RESULTS: A total of 76 patients relapsed during the period of study. The diagnostic accuracy was 83% for CEA and 88% for CA 15-3. CEA and CA 15-3 had a positive predictive value of 27% and 47% as well as a negative prediction of 91% and 93%, respectively (Sütterlin M. et al., 1999).

- CEA levels were determined in 298 mammary tissue samples (30 benign, 242 primary breast cancer and 26 metastatic breast cancer). CEA serum levels were also evaluated in 30 patients with benign diseases, 153 patients with primary breast cancer and 26 patients with metastases. CEA tissue levels in both pellet and cytosol were significantly higher in samples from cancerous than from non malignant tissues, and higher in the pellet than in the cytosol. CEA in the pellet and cytosol were related to steroid receptors, with the highest levels being observed in ER+/PgR+ tumors. They were, however, not related to other pathological parameters such as tumor size or nodes. There was a correlation between CEA pellet and CEA serum in both patients with primary or metastatic tumors, with significantly higher CEA serum levels in patients with CEA pellet positivity than in those with CEA pellet negativity. CEA serum levels were a prognostic factor (disease-free survival and overall survival) in the whole group as well as in node-positive and node-negative breast cancer patients. This prognostic value was only found in patients with CEA pellet positivity (Molina R. et al., 1999).

- In 158 mastectomized breast cancer patients with equivocal bone scintigraphy (BS), prolonged clinical and imaging follow-up over 45 months (mean; range 12-120) was used to ascertain the presence or absence of bone metastases. In these 158 patients the negative predictive value and positive predictive value of the CEA-Tissue polypeptide antigen (TPA)-CA15.3 tumour marker panel to predict bone metastases was 97% and 75% respectively. Thus, in breast cancer patients, the CEA-TPA-CA15.3 tumour marker panel could have a high value in selecting those patients with bone metastases, or at high risk of developing clinically-evident bone metastases, among the large number of subjects with equivocal BS (Nicolini A. et al., 1999).


References

Bostick P.J. et al. (1998) Limitations of specific reverse-transcriptase polymerase chain reaction markers in the detection of metastases in the lymph nodes and blood of breast cancer patients. J. Clin. Oncol. 16, 2632-2640.
Cournoyer D. et al. (1988) Transcription of genes of the carcinoembryonic antigen family in malignant and nonmalignant human tissues. Cancer Res. 48, 3153-3157.
Ebeling F.C. et al. (1999) Tumour markers CEA and CA 15-3 as Prognostic factors in breast cancer--univariate and multivariate analysis. Anticancer Res. 19, 2545-2550.
Gold P. and Freedman S.O. (1965) Demonstration of tumor-specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J. Exp. Med. 121, 439-462.
Kamarck M.E. et al. (1987) Carcinoembryonic antigen family: expression in a mouse L-cell transfectant and characterization of a partial cDNA in bacteriophage lambda-gt11. Proc. Natl. Acad. Sci. USA 84, 5350-5354.
Molina R. et al. (1999) Carcinoembryonic antigen in tissue and serum from breast cancer patients relationship with steroid receptors and clinical applications in the prognosis and early diagnosis of relapse. Anticancer Res. 19, 2557-2562.
Mori M. et al. (1998) Clinical significance of molecular detection of carcinoma cells in lymph nodes and peripheral blood by reverse transcription-polymerase chain reaction in patients with gastrointestinal or breast carcinomas. J. Clin. Oncol. 16, 128-132.
Nicolini A. et al. (1999) The role of tumour markers in predicting skeletal metastases in breast cancer patients with equivocal bone scintigraphy. Br. J. Cancer 79, 1443-1447.
Oikawa S. et al. (1987) Primary structure of human carcinoembryonic antigen (CEA) deduced from cDNA sequence. Biochem. Biophys. Res. Commun. 142, 511-528.
Sütterlin M. et al. (1999) Predictive value of CEA and CA 15-3 in the follow up of invasive breast cancer. Anticancer Res. 19, 2567-2570.
Thompson J. et al. (1992) Long-range chromosomal mapping of the carcinoembryonic antigen (CEA) gene family cluster. Genomics 12, 761-772.
Zimmermann W. et al. (1987) Isolation and characterization of cDNA clones encoding the human carcinoembryonic antigen reveal a highly conserved repeating structure. Proc. Natl. Acad. Sci. USA 84, 2960-2964.
Zippelius A. et al. (1997) Limitations of reverse-transcriptase polymerase chain reaction analyses for detection of micrometastatic epithelial cancer cells in bone marrow. J. Clin. Oncol. 15, 2701-2708.


See also

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