The study, "Mammaglobin A: A Promising Marker for Breast Cancer," was prepared by Neil O'Brien, Niamh Lynch, and Michael J. Duffy of St. Vincent's University Hospital in Dublin, Ireland; and Teresa M. Maguire, Norma O'Donovan, Arnold D. K. Hill, Enda McDermott, and Niall O'Higgins from University College, Dublin. It appears in the latest edition of Clinical Chemistry, the scientific journal of the American Association for Clinical Chemistry (AACC), and its publication coincides with the organization’s 54th Annual Meeting. AACC (www.aacc.org) is the scientific organization for clinical laboratory professionals, physicians, and research scientists. Their primary commitment is the understanding of laboratory testing to identify, monitor and treat human disease. More than 11,000 attendees are expected for the meeting, which is being held at the Orange County Convention Center in Orlando, FL, July 28-August 1, 2002.
Background
Cancer researchers once believed that most tumor markers lacked organ-specificity. However, this view has been abandoned in light of breakthroughs in the identification of prostate cancer-specific markers. Scientific understanding was further advanced when researchers identified a novel gene that is expressed only in breast cancer. This novel gene was designated "mammaglobin" (MG). In subsequent studies, the MG protein was detected in 81 percent of breast cancers, with MG mRNA found to be many times higher in breast carcinomas than in normal breast tissue.
In 1998, researchers discovered a new gene with a sequence similar to MG. Accordingly, this gene was named mammaglobin B (MGB), and the original mammaglobin gene was renamed MGA. MGA, MGB, and several related genes, such as lipophilin B (LPB), are localized in a dense cluster on chromosome 11q12.2 and have been associated with human breast cancer.
Methodology
The research team set out to measure the expression of MGA, MGB, and LPB in different types of breast tissues, as well as in some non-breast tissues. For the breast carcinomas, the researchers also examined the combined expression of MGA, MGB and LPB.
A total of 21 normal breast tissue samples, 32 fibroadenoma (non-breast) samples and 142 breast carcinoma tissue samples were examined. Breast cancer tissues were assayed for estrogen receptors and for a progesterone receptor using ELISA. Total RNA was extracted and cDNA amplification was performed.
Results
The distribution of MGA, MGB, and LPB mRNA expression were examined in the tissue samples. The most significant findings of the study revealed that:
- A significant positive correlation exists between expression of MGA and LPB in breast carcinomas.
- MGA was found more frequently in estrogen receptor-positive versus estrogen receptor-negative carcinomas (72 percent vs. 45 percent). LPB had the same relationship, while MGB displayed no relationship to estrogen-receptor status.
- Among the 97 cancers studied for all three transcripts, nearly half (41 percent) were positive for MGA, MGB and LPB, while 78 percent of cancers expressed at least one of these genes.
- Among the 24 non-malignant non-breast tissues, MGA was found in only one sample, and was absent from eight non-breast carcinomas. MGB was found in four of 15 non-malignant breast tissues and in one of seven non-breast malignant samples. LPB was prominent in both.
- For each mRNA species, the frequency of expression was similar in each of the categories examined.
Conclusions
These findings could have monumental consequences for breast cancer screening. Because MGA is mostly (but not exclusively) confined to breast tissue, this gene may be one of the first relatively mammary-specific markers. It's potential applications include (1) the detection of breast cancer micrometastases in lymph nodes, peripheral blood and bone marrow; (2) identification of metastases of unknown origin, and (3) early detection of breast cancer.
Editor’s Note: To interview a member of the research team, please contact
Donna Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell)
or djkrupa1@aol.com.
Or contact the AACC Newsroom at: 407.685.4215.