Urinary concentrations of ADAM 12 from breast cancer patients pre- and post-surgery vs. cancer-free controls: a clinical study for biomarker validation.

Abstract

Background: The ADAMs (A Disintegrin and Metalloproteinases) are a family of multi-domain, zinc-dependent metalloproteinase enzymes. ADAM 12 has been previously associated with the onset and progression of breast cancer, and elevated levels of ADAM 12 have been previously found in the urine of breast cancer patients. Aims of the current study are: 1) establish the viability of urinary ADAM 12 as a diagnostic marker for breast cancer, and 2) explore the effects of surgical tumor removal on the levels of urinary ADAM 12.

Methods: A total of 96 patients have been recruited for this study, including 50 patients diagnosed with cancer, and 46 age-matched controls. Commercially available ELISA kits for ADAM 12 were used to quantify the presence and concentration of this enzyme in the urine from cancer patients with ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) both prior to any treatment and approximately two weeks following surgery, as well as from controls.

Results: We find no statistically significant differences between the concentrations of ADAM 12 in the urine of breast cancer patients prior to treatment and that of their age-matched controls; however the concentration of ADAM 12, both alone and as a function of urine total protein, are significantly elevated following surgery (p < 0.0001). Patients who underwent a mastectomy have significantly higher urinary ADAM 12 concentrations than those who underwent a lumpectomy (significant at p = 0.0271).

Conclusions: These findings suggest that urinary ADAM 12 may not correlate directly with the status and stage of breast cancer as previously thought; rather these increases may be a result of tissue injury and inflammation from biopsy and surgical resection. Results of this study may suggest a need for biomarkers to be evaluated carefully in the context of tissue damage.