Ror Gamma T May Influence The Microenvironment Of Thyroid Cancer Predicting Favorable Prognosis

We aimed to investigate the role of ROR gamma t (Retinoic acid-related orphan receptor gamma) in the tumor microenvironment of differentiated thyroid carcinoma. We retrospectively analyzed 56 patients (48 papillary and 8 follicular thyroid carcinomas). Immunohistochemical expression of ROR gamma t was compared to other immune markers previously investigated by our group, clinical and pathological information. All patients presented cytoplasmic expression of ROR gamma t in thyroid tumor cells. Seven (12.5%) patients presented no nuclear expression of ROR gamma t. Positivity was few (up to 10%) in 14 patients; 10 to 50% in 5 patients (8.9%); and more than 50% in 30 patients (53.6%). Nuclear ROR gamma t positivity was associated with absence of distant metastasis at diagnosis (p = 0.013) and the need of less cumulative doses of radioactive iodine (p = 0.039). Patients whose tumors were positive for nuclear ROR gamma t presented higher 10-years relapse-free survival rate than those patients who were negative for ROR gamma t (p = 0.023). We classified the patients according to the clustering of immunological immunohistochemical markers. We were able to distinguish a subset (A) of 38 patients who presented high expression of nuclear ROR gamma t and tended to be scarce in proinflammatory immune markers. Other 16 patients integrated a second subset (B) whose tumor microenvironment accumulated proinflammatory markers and presented low expression of nuclear nuclear ROR gamma t. Distant metastasis at diagnosis were more frequent among patients from cluster B than from cluster A (p = 0.008). Our results reinforce that the expression of ROR gamma t together with other immune markers might help predict the prognosis of patients with thyroid cancer and help individualize clinical management.