Expression of metalloproteinases and their tissue inhibitors in squamous cell laryngeal carcinoma.

ABSTRACT

The hallmark of cancer invasion is the degradation of extracellular matrix components. Matrix metalloproteinases are the major enzymes participating in this event and their activity is regulated extracellularly by their presence as proenzymes and the concomitant presence of the specific tissue inhibitors. The present study describes the immunohistochemical localization of gelatinases, matrix metalloproteinase (MMP)-2 and -9 and tissue inhibitor of metalloproteinase (TIMP)-1 and -2 in human laryngeal carcinoma and their expression with respect to tumor classification and compared with the respective healthy subjects. MMP-2 was immunolocalized in the cytoplasm of the epithelial cells and in the loose connective tissue, whereas MMP-9 was also observed in basement membrane and chondrocytes. Both were also found in tumor cells, but staining was decreased with increasing stage of cancer. TIMP-1 was present exclusively in stroma and totally absent from tumor cells and it was overexpressed in normal cells surrounding the tumor. TIMP-2 was identified in the cytoplasm of epithelial cells, in stroma and sometimes in chondrocytes. In addition, it was present in tumor cells of only stage IV samples. The expression level of both gelatinases and TIMPs increased as the stage of cancer increased, suggesting the possible post-transcriptional removal of their mRNA. These observations, performed in a given head and neck site, suggest that the behavior of head and neck tumors seems to depend on the site and additional studies should be performed to obtain a general understanding of the disease and ascertain the role of the constituents examined.