Serum mammastatin - Tips from the clinical experts

Medical Laboratory Observer, August, 2003 by Daniel M. Baer

Q Can you tell me about serum mammastatin as an indicator for breast cancer or as a risk indicator for breast cancer?

A Mammastatin was first described as a growth-inhibiting protein by Paul Ervin, Jr., PhD, at the University of Michigan in 1989. He started Biomedical Diagnostics LLC, Ann Arbor, MI, a biotechnology research and development company specifically focused on bringing mammastatin products, such as therapeutic mammastatin and the mammastatin blood test, to market.

Mammastatin is detected in the mammary duct epithelial cells of normal breast tissue, and it is secreted into the blood--but is not found in breast milk. Three forms of the protein are detected, although only the largest, a 53-kD protein, is phosphorylated and, therefore, active. In breast tissue of patients with breast cancer, neither the cancer cells nor the normal mammary duct epithelial cells contain the 53-kD form, although both benign and malignant breast epithelial cells may or may not have the smaller molecular forms. So, it seems that the absence of the ability to make the active mammastatin molecule is an indicator that a woman may be at risk for developing breast cancer. An immunoblot assay for the 53-kD form of mammastatin, Mammastatin Serum Assay (MSA), has been developed by Biomedical Diagnostics. In June 2001, an agreement with ARUP Laboratories, an independent reference laboratory in Salt Lake City, UT, gave it the worldwide rights to market and service the MSA. ARUP continues to send specimens to Biomedical Diagnostics for testing as of this date. Immunoblot assays are usually qualitative assays, but this one has been made to be crudely semiquantitative by measurement of the density of the blot and reported as "Relative Density Units," which is a comparison to a standard curve prepared with known concentrations of mammastatin.

The specimen for the assay is 4-cc serum, refrigerated after separation from the clot at room temperature. Do not use a serum separator tube to collect the sample. Hemolysis invalidates the specimen. Results are reported within one week. The cost is about $200.

The assay has been assigned "research use only" status by the FDA, although a short-term level 1 study has been completed and an application to FDA for pre-market approval is being prepared. At this time, Biomedical Diagnostics and ARUP tell us that the results are intended for informational purposes. If the value is low, the risk of having the cancer is high; and higher values mean the risk is lower. First estimates suggest that a low MSA value gives the woman a 1-in-3 to 1-in-6 chance of having breast cancer and may be predictive of subsequent development of breast cancer. High levels of the protein are said to be helpful in reducing a patient's fear of developing breast cancer. Patients with low values are advised to seek mammogram or further evaluation.

--Louis Buettner, MD

Consulting Pathologist

Dynacare--Alabama Reference

Laboratories/LabSouth

Tuscaloosa, AL

References

(1.) Ervin PR, et al. Production of mammastatin, a tissue-specific growth inhibitor, by normal human mammary cells. Science June 30,1989;244(4912):1585-1587.

(2.) Ervin PR, et al. Differential expression of mammastatin in normal and breast cancer cells. Breast Cancer Res 2000; 2:E009.

(3.) ARUP. Mammastatin Serum Assay[TM]. Available at: www.arup-lab.com/guides/clt/tests/clt_a61b.htm. Accessed April 4, 2002.

(4.) Biomedical Diagnostics. Information for doctors--scientific overview of mammastatin. Available at: www.bio-diagnostics.com/information_for_doctors.html. Accessed April 4, 2002.

Daniel M. Baer is professor emeritus of laboratory medicine at Oregon Health and Science University in Portland, OR and a member of MLO's editorial advisory board.