Role of Ki-67 proliferation index and p53 expression in predicting progression of pituitary adenomas

Pituitary adenomas sometimes progress after surgery and can be locally invasive. Ki-67 and p53 expression are referred to as indicators of aggressive behavior in the World Health Organization Classification of Endocrine Tumors. The real value of these markers including an appropriate threshold for Ki-67 labeling index correlating with tumor progression is controversial. We identified 24 consecutive pituitary adenomas from patients who required surgery for recurrence within 5 years of their first procedure and 31 consecutive adenomas with no evidence of postsurgical progression within 5 years of first surgery. Case selection was based upon availability of complete clinical information, blocks, and slides for study. Immunohistochemistry for Ki-67 revealed that the tumors without progression had a proliferation index of 0.41% +/- 0.01% (mean +/- SEM) (n = 31) (range, 0.08%-1.2%) and the first biopsy from those tumors which progressed had a mean proliferation index of 1.45% +/- 0.09% (mean +/- SEM) (n = 24) (range, 0.1%-10.6%) (P = .01). With the use of ROC analysis, a threshold level of Ki-67 expression greater than 1.3% predicts progression with a high specificity. The group with progression had a higher proportion of nonfunctioning tumors (P < .005, chi(2)). There was no significant difference between the 2 groups with regard to invasion, suprasellar extension, size, tumor type, postoperative radiotherapy, extent of resection, sex, and age. Ki-67 labeling index was an independent predictor of progression (multivariate analysis, P < .011). p53 was positive in 12.5% of cases with surgical progression and in 9.6% of cases without progression, but the difference was not significant (P = .7; chi(2), 0.11).