The Involvement of RCAS1 in Creating a Suppressive Tumor Microenvironment in Patients with Salivary Gland Adenocarcinoma.

The tumor microenvironment is the tissue that determines the growth and progression of the tumor as well as its ability to initiate metastases. The aim of the present study has been to evaluate the role of RCAS1 in creating the suppressive tumor microenvironment in cases of parotid adenocarcinoma. The tissue samples of salivary gland adenocarcinomas and their stroma and the palatine tonsils which constituted the reference tissue sample group were obtained during routine surgical procedures. The immunoreactivity of RCAS1, CD3, CD25, CD68, CD69, and Foxp3 antigens was then evaluated by using the immunohistochemistry method. The patient's consent was obtained in each case. A statistically significantly higher RCAS1 immunoreactivity level was found in the adenocarcinoma tissue samples in comparison to that found in the stromal tissue samples. A statistically significantly higher RCAS1 immunoreactivity was also identified in the adenocarcinoma tissue samples derived from patients who had lymph node metastases in comparison to patients without such metastases. Additionally, we observed the presence of RCAS1-positive macrophages in the stromal tissue samples. The infiltration of CD68-positive cells was significantly stronger in the adenocarcinoma and stromal tissue slides than in the reference group tissue slides; moreover, the infiltration was a good deal more prominent in the stromal tissue than in the adenocarcinoma tissue. The CD68 immunoreactivity levels in both the tumor and stromal tissue samples were found to be significantly higher in those patients who had lymph node metastases than in the patients without such metastases. Additionally, the infiltration of CD3- and CD25-positive cells was more prominent in the reference tissue slides than in the adenocarcinoma and stromal tissue slides, and was stronger in the adenocarcinoma tissue than in the stromal tissue. Furthermore, the infiltration of Foxp3-positive cells was seen exclusively in the stroma whereas it was not even detected in the adenocarcinoma tissue. Lastly, the Foxp3-positive cell infiltration was more prominent in the stromal tissue than in the reference group tissue. The present study demonstrates that RCAS1 expression by both tumor cells and tumor-associated macrophages may participate in creating the immunosuppressive microenvironment in parotid gland adenocarcinoma, thus promoting tumor development as well as metastases.