OVEREXPRESSION OF STROMELYSIN-3, BM40 SPARC, AND MET GENES IN HUMAN ESOPHAGEAL-CARCINOMA - IMPLICATIONS FOR PROGNOSIS/

Molecular markers can improve staging and predict aggressive clinical behavior in esophageal cancer, thus helping to define appropriate ther apeutic protocols and to identify patients who will benefit from surge ry. We therefore characterized, by Northern blot and/or immunohistoche mistry, the relative expression of three effecters involved in the inv asion, angiogenesis, and dissemination of tumor cells in esophageal ca ncer versus nontumoral mucosae: (a) stromelysin-3 (ST3), a member of t he metalloproteinase family; (b) basement membrane 40/secreted protein acidic and rich in cysteine (BM-40/SPARC), an extracellular matrix-as sociated protein involved in angiogenesis; and (c) the hepatocyte grow th factor receptor MET, which triggers the scattering of epithelial ce lls. Results were analyzed in relation to clinicopathological paramete rs (cpTNE) including tumor size (T), lymph node status (N), periesopha geal tissue invasion (E), disease recurrence, and overall survival. Th e ST3, BM-40/SPARC, and MET genes were found to be overexpressed in tu mor samples compared to control mucosa, BM-40/SPARC and MET mRNA level s were not linked to any one of the cpTNE, indicating that this overex pression occurs at an early stage of neoplastic progression. In contra st, ST3 expression, identified by immunohistochemistry in fibroblastic cells surrounding neoplastic islets, correlated with tumor size and p eriesophageal tissue invasion. Of the 36 patients studied, those with high ST3 levels had shorter disease-free survival than those with low levels, but there was no relationship between the cpTNE and disease re currence or survival. Our study demonstrates that ST3, BM-40/SPARC, an d MET are involved in different steps of esophageal carcinogenesis and that ST3 overexpression is a marker of aggressive clinical behavior. We conclude that in esophageal cancer, ST3 might help to assess surviv al and the risk of recurrence after surgical resection.