Reply to: Serum samples should not be used to access circulating matrix metalloproteinase‐9 levels as a prognostic marker of disease

Abstract

Dear Sir,We thank Tanus-Santos and Gerlach for the special interest to our work regarding the serum matrix metalloproteinase-9 as a prognostic marker in head and neck squamous cell carcinoma 1 .In our study, we demonstrated that high preoperative serum MMP-9 levels were linked with poor cause-specific as well as poor relapse-free survival in head and neck squamous cell carcinoma patients.1 The median serum level for MMP-9 immunoreactive protein of HNSCC patients was 89.9 ng/ml and the mean value was 115.2 ng/ml. Additionally, we demonstrated that the MMP-9 levels in 44 healthy controls were lower, median 55.6 ng/ml, mean 69.7 ng/ml (p < 0.001). The levels of MMP-9 immunoreactive protein in our study are thus clearly in line with studies published previously concerning MMP-9 serum levels in HNSCC patients 2,3 and the MMP-9 levels in controls equal the control plasma levels in study by Jung et al. 4 Moreover, Jung et al.4 have compared the serum and plasma levels of MMP-9 immunoreactive protein among controls using serum samples collected with or without tubes based on additives with clot activator. In our study, the serum samples were all so-called native serum samples i.e., collected with tubes with no additives. We also want to point out the fact that in our study all samples have been handled in consistent method. This fact would have been very important to add to the Material and Methods section and we are very grateful to have this opportunity to clarify the issue. In general, the pre-analytical conditions and methodological issues are essential when assessing MMP-9 in clinical samples. 4,5 When evaluating the immunoreactive protein by ELISA assay, it should not equate with the assay of measuring the activities of MMP-9. [6][7][8] The source of circulating MMP-9 whether it is measured from serum or plasma is not easy to define. In our study, however, we were also able to show that there is a statistically significant correlation between the serum level of MMP-9 immunoreactive protein and MMP-9 immunohistochemical staining in primary tumors of HNSCC.