Detection of occult metastatic breast cancer cells in blood by a multimolecular marker assay: correlation with clinical stage of disease.
Cancer Res
; 61(24): 8845-50, 2001 Dec 15.
Article
in En
| MEDLINE
| ID: mdl-11751407
ABSTRACT
Currently, molecular markers offer the unique opportunity to identify occult metastasis in early stage cancer patients not otherwise detected with conventional staging techniques. To date, well-characterized molecular tumor markers to detect occult breast cancer cells in blood are limited. Because breast tumors are heterogeneous in tumor marker expression, we developed a "multimarker" reverse transcription-PCR assay combined with the highly sensitive electrochemiluminescence automated detection system. Breast cancer cell lines (n = 7), primary breast tumors (n = 25), and blood from normal donors (n = 40) and breast cancer patients [n = 65; American Joint Committee on Cancer (AJCC) stages I-IV] were assessed for four mRNA tumor markers beta-human chorionic gonadotropin (beta-hCG), oncogene receptor (c-Met), beta 1-->4-N-acetylgalactosaminyl-transferase, and a tumor-associated antigen (MAGE-A3). None of the tumor markers were expressed in any normal donor bloods. Breast cancer cell lines and primary breast tumors expressed beta-hCG, c-Met, beta 1-->4-N-acetylgalactosaminyl-transferase, and MAGE-A3 mRNA. Of the 65 breast cancer patient blood samples assessed, 2, 3, 15, 49, and 31% expressed 4, 3, 2, 1, and 0 of the mRNA tumor markers, respectively. At least two markers were expressed in 20% of the blood specimens. The addition of a combination of markers enhanced detection of systemic metastasis by 32%. In patient blood samples, the MAGE-A3 marker correlated significantly with tumor size (P = 0.0004) and AJCC stage (P = 0.007). The combination of beta-hCG and MAGE-A3 mRNA markers correlated significantly with tumor size (P = 0.04), and the marker combination c-Met and MAGE-A3 showed a significant correlation with tumor size (P = 0.005) as well as AJCC stage (P = 0.018). A multimarker reverse transcription-PCR assay that correlates with known clinicopathological prognostic parameters may have potential clinical utility by monitoring tumor progression with a blood test.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Biomarkers, Tumor
/
Neoplastic Cells, Circulating
/
Neoplasm Proteins
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
Language:
En
Journal:
Cancer Res
Year:
2001
Document type:
Article
Affiliation country:
United States