The Potential Role of MT and Vimentin Immunoreactivity in the Remodeling of the Microenvironment of Parotid Adenocarcinoma

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.