KI-67 labeling index and expression of P53 are non-predictive on invasiveness and tumour size in functional and nonfunctional pituitary adenomas: A large series of 421 patients

Introduction: The nuclear protein KI-67 is a marker for cellular proliferation and its expression level correlates significantly with tumour growth rate of pituitary adenomas. Together with excessive p53 activity, atypical adenomas are defined by a KI-67 labeling index (LI) > 3%. Nevertheless it is still controversially discussed whether an increased proliferation index is correlated with the tumour invasiveness, which is a major criteria for operability and long-term remission after surgery. In this large monocentric case study we investigated the correlation between the proliferation indices (KI-67 and p53 expression levels) and invasiveness and size of pituitary adenomas.

Methods: 421 patients who underwent transsphenoidal or transcranial resection of pituitary adenomas were retrospectively included (51 ± 16.5 years, 207 non-functioning adenomas, 32 growth hormone secreting adenomas, 59 corticotroph adenomas, 56 prolactinomas, 4 TSH-secreting adenomas). Preoperative T1 contrast enhanced MRI were retrospectively evaluated concerning mean tumor diameters and tumour invasiveness (Knosp Index). Expression indices of KI-67 and p53 were immunohistochemically examined at our Department of Neuropathology. Correlation of mean tumour volume and the proliferation indices was calculated using a robust linear regression. One way Anova Analysis or a student t-test was performed to discriminate between proliferation indices and Knosp grade or invasiveness (Knosp 3 and 4), respectively.

Results: The average values of KI-67 LI was 2.42 ± 3.85 [0.00; 70.00] while mean p53 expression was 3.00 ± 4.24 [0.00; 50.00]. Overall and in the subgroups no significant correlation between proliferation indices and mean tumour volume was found. There was no significant predictive expression value of KI-67 and p53 on tumour invasiveness (p > 0.5).

Conclusion: In this evaluation of the large monocentric series we conclude that there is neither a significant correlation with tumor size nor with invasiveness of secreting and non-secreting pituitary adenomas regarding immunohistochemical expression levels/indices of KI-67 and p53. These findings suggest that invasive behaviour is a feature independent from proliferation.