Role of YAP-1 in Thyroid Tumor Progression and Outcome

Context: Yes-associated protein-1 (YAP-1) is a player of the Hippo pathway and is involved in regulating cell proliferation. YAP-1 is overexpressed in papillary and anaplastic thyroid cancers. However, a correlation between YAP-1 expression and outcome in thyroid carcinoma has not been conclusively demonstrated. Objective: This study was designed to clarify whether YAP-1 may be considered a marker of worse prognosis and outcome in thyroid cancer. Design: A large series of cases of thyroid cancer with a long follow-up were investigated for YAP-1 expression. Setting: The study was carried out in the Pathology section of a referral Italian center for Endocrine Surgery and Endocrinology. Patients or Other Participants: The study included a consecutive series of 105 patients who underwent thyroidectomy from 1985 to 1992. The mean follow-up was 15 years. For all patients, clinicopathologic features were considered. All patients completed the study. The study also included a consecutive series of 52 patients who underwent thyroidectomy from 2012 to 2013 in order to analyze more deeply the correlation of YAP-1expression with BRAF mutation. Intervention: The 105 thyroid tumors were immunohistochemically investigated for YAP-1 expression. Outcome Measures: We expected a correlation between YAP-1 expression and worse prognosis. Results: Among 105 tumors, 77 scored positive for YAP-1 expression, of which 68 papillary thyroid carcinomas and 9 anaplastic thyroid carcinomas were YAP-1 positive. The correlation of YAP-1 expression with clinicopathologic characteristics was significant for the absence of a tumoral capsule, gender, and extrathyroid invasion. Interestingly, significant correlations were found between YAP-1 and both persistence of disease and death from carcinoma. Conclusions: The data show an association of YAP-1 expression with worse clinicopathologic features of thyroid tumors that seem to have a specific impact on outcome.