Tenascin in human neoplasia

Tenascin (TN), a recently characterized extracellular matrix protein, largely confined to the process with the development of embryo in areas of epithelial-mesenchymal interactions, developing neural tissues, bone and cartilage where there are morphogenetic movements and tissue patterning, has a highly restricted expression in adult tissues. The function(s) and molecular mechanisms of enhanced expression of TN in neoplastic lesions, however, remain unclear. Tissue specimens of human neoplasia obtained from 1050 cases of biopsy or surgery and their representative fetal and normal adult tissues were evaluated for immunoreactivity of TN using seven different clones of monoclonal antibodies in a three stage streptavidin biotin immunoperoxidase method. The normal epithelial lined structures such as the mucous membrane and skin had a thin delicate immunoreactive band just beneath the basement membrane at the epithelial mesenchymal interface. Hyperplastic or dysplastic lesions of the epithelium, such as leukoplakia of the oral mucosa, senile keratosis and intraepithelial carcinoma of skin showed an enhanced expression of TN extending down into the connective tissue where the degree of enhanced expression correlated with increasing hyperplasia or dysplasia. The squamous cell carcinoma and adenocarcinoma of different organs, both at the primary site and in lymph node metastasis, showed a widespread stromal immunoreactivity and the expression was affected by infiltration of inflammatory cells, fibrous tissue reaction and tumor cell differentiation. There was heterogeneity in the expression of TN in benign epithelial neoplasms, squamous cell carcinoma and adenocarcinoma which varied in different areas of the same tumor specimen ranging from no reaction to intensely reactive areas. The undifferentiated carcinomas often had low expression in the stroma. The non-epithelial or mesenchymal tumors such as chondrogenic, osteogenic, myogenic, neurogenic, vascular and other miscellaneous neoplasms also had an enhanced expression of TN. When the immunoreactivity of seven different monoclonal antibodies to detect TN were compared, the pattern of expression of TN with different monoclonal antibody in majority of the cases were identical and equivocal, but there were slight differences in the intensity of staining. Using a single monoclonal antibody nearly 94% of the cases of human neoplasia showed an enhanced immunoreaction for TN. In conclusion, the results of the present study when combined with our previous in vitro study (Shrestha et al, Eur J Cancer Oral Oncol, in press) suggest that the enhanced expression of TN in vivo in a wide variety of neoplastic lesions of both epithelial and non-epithelial in origin may affect tumor growth, differentiation, vascularity, cellular adhesion, invasion and metastasis.