A
tumor stimulates the remodeling of its microenvironment in order to control and accelerate its own growth and to initiate
metastases. To create
metastases the
tumor cells must first acquire the ability to detach from the main
tumor and to adhere to, invade, and degrade the adjacent extracellular matrix. The cells must then be able to enter the lumen of the vessels where they home the distant tissues and organs by forming secondary
tumors. The acquisition of this phenotype is related to the phenomenon of epithelial-to-mesenchymal transition. On the molecular level, this process is typified by a change in the expression of epithelial markers and by the enhancement of the expression of mesenchymal markers like
vimentin that are responsible for cell migration and invasion.
Metallothioneins have been shown to help protect against apoptosis. The expression of MT by
tumor cells plays an important and complex role not only because of its pro-proliferative, anti-apoptotic activity, but also because it inhibits the immune response. The aim of the present study was to evaluate the immunoreactivity of
vimentin and MT in the salivary gland
adenocarcinoma and its stroma in order to observe the phenomenon of stromal remodeling. The tissue samples of salivary gland
adenocarcinomas and their stromas and the palatine tonsils which constituted the reference group were obtained during routine
surgical procedures. The immunoreactivity of
vimentin, metalothionein, CD56,
CD57 antigens was evaluated by the immunohistochemistry method in 30 tissue samples of parotid
adenocarcinoma. The patient's consent was obtained in each case. A statistically significantly higher level of MT immunoreactivity was observed in the
adenocarcinoma tissue slides than in either the stromal slides or the reference slides while no differences in MT immunoreactivity were detected when the stroma and reference tissue slides were compared. A statistically significantly higher
vimentin immunoreactivity level was identified in the tumor microenvironment tissue slides than in the
tumor tissue slides, and a statistically significantly higher level of
vimentin immunoreactivity was identified in the tumor microenvironment slides than in the slides of the reference tissue, while no differences were identified between the
adenocarcinoma tissue slides and the reference slides with respect to
vimentin immunoreactivity. A statistically significantly higher number of CD56- and CD57-expressing cells were identified in the reference tissue slides than in either the
adenocarcinoma or stromal slides. In conclusion, the stroma of salivary gland
adenocarcinoma in this study has been characterized by remodeling. The remodeling is represented by the expression of both
vimentin and MT and by a deficit of CD57- and CD58-expressing cell infiltration. This situation would seem to be the result of immune tolerance for the
tumor developing within the tumor microenvironment. Furthermore, the presence of MT and
vimentin immunoreactivity in the fibroblasts of the
tumor stroma may constitute a marker of active tissue remodeling.