Detection of occult metastatic breast Cancer cells in blood by a multimolecular marker assay: Correlation with clinical stage of disease

• Published in: Cancer research (Chicago, Ill.) Vol. 61; no. 24; pp. 8845 - 8850
• Main Authors: TABACK, Bret, CHAN, Arden D, KUO, Christine T, BOSTICK, Peter J, WANG, He-Jing, GIULIANO, Armando E, HOON, Dave S. B
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.12.2001
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - blood; Antigens, Neoplasm - genetics; Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Breast Neoplasms - blood; Breast Neoplasms - pathology; Choriocarcinoma - genetics; Choriocarcinoma - metabolism; Chorionic Gonadotropin, beta Subunit, Human - biosynthesis; Chorionic Gonadotropin, beta Subunit, Human - blood; Chorionic Gonadotropin, beta Subunit, Human - genetics; Female; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; N-Acetylgalactosaminyltransferases - biosynthesis; N-Acetylgalactosaminyltransferases - blood; N-Acetylgalactosaminyltransferases - genetics; Neoplasm Proteins; Neoplasm Staging; Neoplastic Cells, Circulating - metabolism; Neoplastic Cells, Circulating - pathology; Proto-Oncogene Proteins c-met - biosynthesis; Proto-Oncogene Proteins c-met - blood; Proto-Oncogene Proteins c-met - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - blood; RNA, Messenger - genetics; Sensitivity and Specificity; Tumor Cells, Cultured; Tumors; Human; Methodology; Biological marker; Tumoral marker; Metastasis; Malignant tumor; Gene expression; In vitro; Blood; Mammary gland diseases; Clinical stage; Investigation method; Tumor progression; Micrometastasis; Metastatic; Mammary gland; Detection; Reverse transcription polymerase chain reaction; Tumor cell
• ISSN: 0008-5472; 1538-7445

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.