ABSTRACT
Molecular markers can improve staging and predict aggressive clinical behavior in esophageal cancer, thus helping to define appropriate therapeutic protocols and to identify patients who will benefit from surgery. We therefore characterized, by Northern blot and/or immunohistochemistry, the relative expression of three effectors involved in the invasion, angiogenesis, and dissemination of tumor cells in esophageal cancer versus nontumoral mucosae: (a) stromelysin-3 (ST3), a member of the metalloproteinase family; (b) basement membrane 40/secreted protein acidic and rich in cysteine (BM-40/SPARC), an extracellular matrix-associated protein involved in angiogenesis; and (c) the hepatocyte growth factor receptor MET, which triggers the scattering of epithelial cells. Results were analyzed in relation to clinicopathological parameters (cpTNE) including tumor size (T), lymph node status (N), periesophageal tissue invasion (E), disease recurrence, and overall survival. The ST3, BM-40/SPARC, and MET genes were found to be overexpressed in tumor samples compared to control mucosa. BM-40/SPARC and MET mRNA levels were not linked to any one of the cpTNE, indicating that this overexpression occurs at an early stage of neoplastic progression. In contrast, ST3 expression, identified by immunohistochemistry in fibroblastic cells surrounding neoplastic islets, correlated with tumor size and periesophageal 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 recurrence or survival. Our study demonstrates that ST3, BM-40/SPARC, and 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 survival and the risk of recurrence after surgical resection.
Subject(s)
Adenocarcinoma/pathology , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Metalloendopeptidases/biosynthesis , Osteonectin/biosynthesis , Proto-Oncogene Proteins c-met/biosynthesis , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adult , Aged , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Disease-Free Survival , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/mortality , Esophageal Neoplasms/surgery , Esophagectomy , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , Matrix Metalloproteinase 11 , Metalloendopeptidases/analysis , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Osteonectin/analysis , Polymerase Chain Reaction , Prognosis , Proto-Oncogene Proteins c-met/analysis , Survival Rate , Time FactorsABSTRACT
Investigations in 6 cases of congenital or acquired athyreosis show that serum thyroglobulin determined in these cases by radioimmunology is not due to a determination artifact or to another protein, but that, with regard to immunoreactivity, molar mass and isoelectric point, it displays all the features of the standard thyroglobulin of thyroid origin and of the serum thyroglobulin of normal subjects. The authors conclude that small quantities of thyroglobulin are present in the serum of such patients, even where all the other criteria of athyrosis appear to be present.
