Ki-67 Expression for Predicting Progression of Postoperative Residual Pituitary Adenomas, and Clinical Features of Atypical Pituitary Adenomas

Objective: Reliable prognostic parameters indicating progression in residual pituitary adenomas after surgery are necessary. The World Health Organization classification of Tumors of Endocrine Organs defines atypical pituitary adenomas as tumor with Ki-67 labeling index higher than 3%, excessive p53, and increased pleomorphism. The real value of a labeling index correlating with tumor progression is controversial.

Materials and Methods: To clarify this value, we investigated and statistically analyzed the relationship between positive labeling for MIB-1 and clinical features of 39 cases of pituitary adenomas with and without progression in the residual adenoma after initial surgery. We also tried to clarify the clinical features of atypical adenomas.

Results: Pituitary adenomas with progression had a mean proliferation index of 3.66% ± 3.00% (mean ± SD), and it was significantly higher than cases without progression of 1.89% ± 1.25% (P < 0.05). With the use of Receiver Operating Characteristic Curve analysis, a threshold level of Ki-67 expression greater than 2.0% predicted progression with high specificity. Other clinical variables included younger patients had higher MIB-1 index and more progression (P < 0.05). Adenomas with cavernous sinus invasion, functioning adenomas, and giant adenomas had higher MIB-1 index (P < 0.05). More completely removed tumors were less progressive. Atypical adenomas revealed recurrence and tended to resist conventional therapies.

Conclusion: A threshold of 2% for the MIB-1 labeling index predicts higher risk of progression of residual adenomas after surgery, shorter term of imaging follow-up, and that early initiation of adjuvant therapy might be required. Atypical adenomas tend to be large, invasive, and resistant to conventional therapies . Temozolomide might be a therapeutic option for invasive atypical adenomas.