Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas. A clinical and immunohistochemical study

Background: The pituitary tumour transforming gene (pttg) plays a central role in pituitary tumorigenesis, but PTTG protein expression is poorly documented and its relationship with tumour cell proliferation and the prognosis of pituitary adenomas is unclear. Aim: The aim of this study was to evaluate the immunohistochemical expression of PTTG and Ki-67 in 45 human pituitary adenomas according to the tumour histotype, aggressiveness and persistence/recurrence status. Patients and methods: The tumours comprised 37 macroadenomas and 8 microadenomas. Twenty patients experienced disease persistence or recurrence after transsphenoidal surgery. Disease recurrence was observed in 16 patients, 8-72 months after surgery. Results: No PTTG or Ki-67 expression was detected in normal pituitary tissue. In pituitary adenomas, tumour nuclei were positive for PTTG and Ki-67 in 89 and 98% of samples, respectively, and there was a strong correlation between the expression of the two proteins (P < 0·001). By the ROC curves method, a PTTG score of 3·3% was the best cut-off for distinguishing between recurrent and nonrecurrent pituitary adenomas (P < 0·05; sensitivity 60%; specificity 76%). A 2·9% cut-off was obtained for both PTTG (P < 0·01; sensitivity 77%; specificity 71%) and Ki-67 (P < 0·05; sensitivity 85%; specificity 64%) among patients with more than 1 year of follow-up. Neither PTTG nor Ki-67 expression was influenced by the maximal tumour diameter, tumour grade, age, gender or presurgical medical treatment. Both PTTG and Ki-67 tumour score > 2·9% identified a subgroup of patients with a significantly higher recurrence-free interval (P < 0·01). By multivariate analysis, a > 2·9% Ki-67 tumour score was the best predictor of pituitary tumour persistence/recurrence after surgery (χ 2 = 8·2, P < 0·01). Conclusion: PTTG is expressed in approximately 90% of pituitary tumours of different histotypes but with a high variability from one case to another. As expected, PTTG expression parallels that of Ki-67 and both are correlated to a more aggressive behaviour. However, a 2·9% Ki-67 cut-off proved to be the most reliable biological marker for predicting the recurrence potential of these tumours, when an adequate postsurgical follow-up is considered. © 2006 The Authors.