The diagnostic criteria for refractory PAs were also proposed as follows: 1) tumor infiltration of adjacent structures according to radiological results or intraoperative findings; 2) Ki-67 index greater than 3%, and growth velocity greater than 2% per month; 3) failure of current treatments to control tumor growth and/or hormonal hypersecretion; and 4) tumor recurrence within 6 months after surgery (37). This evidence concerns the gene MKI67 and neoplasm.