ORIGINAL ARTICLE - PITUITARIES Ki-67 labeling index and expression of p53 are non-predictive for invasiveness and tumor size in functional and nonfunctional pituitary adenomas Florian Grimm 1 & Roland Maurus 1 & Rudi Beschorner 2 & Georgios Naros 1 & Milan Stanojevic 1 & Isabel Gugel 1 & Sabrina Giese 1 & Georg Bier 3 & Benjamin Bender 3 & Jürgen Honegger 1 Received: 25 October 2018 / Accepted: 20 March 2019 # Springer-Verlag GmbH Austria, part of Springer Nature 2019 Abstract Background It is still controversial whether an increased proliferation index is correlated with the tumor invasiveness of pituitary adenomas. A homogeneous large monocentric series of pituitary adenomas was retrospectively analyzed. The correlation between the proliferation indices (Ki-67 and p53 expression levels) and invasiveness and size of pituitary adenomas was investigated in primary operated and recurrent adenomas. Method Four hundred thirty-nine patients after resection of pituitary adenomas were retrospectively included (43 recurrent tumors, 196 null cell adenomas, 86 somatotroph adenomas, 55 corticotroph adenomas, 55 prolactinomas, 4 thyreotroph adeno- mas). The maximum tumor diameter and tumor invasiveness in Knosp grading were assessed and Ki-67 and p53 immunostaining was performed. The role of invasiveness was evaluated using a cumulative odds ordinal logistic regression. For calculating the effect of tumor size, a one-way analysis of variance (ANOVA) was conducted. Results Overall and in the subgroups, no significant correlation between proliferation indices and mean tumor diameter was found. No significant predictive expression value of Ki-67 and p53 on tumor invasiveness and in recurrent tumors could be demonstrated. There was a tendency that Ki-67 LI and p53 LI are higher in recurrent corticotroph adenomas and lactotroph adenomas but values did not reach the significant level. Conclusion Invasive character of pituitary adenomas is neither correlated with increased Ki-67 LI nor with increased p53 expression. Proliferation parameters are independent from adenoma size at initial presentation. The partly elevated expression of Ki-67 in recurrent tumors underlines the clinical importance of the marker. Keywords Pituitary adenomas . p53 . Ki-67 . Invasiveness Background In the 2004 WHO classification of the endocrine organs, pituitary adenomas were divided into typical adenomas, atypical adeno- mas and pituitary carcinomas. The subgroup atypical adenoma was defined by morphological features suggestive of an aggres- sive clinical behavior such as invasive growth, an elevated mitotic index, Ki-67 labeling index (LI) > 3%, and an excessive nuclear p53 immunostaining [7]. This definition led to a wide discussion of the actual clinical implications and to a relatively variable report of the incidence of atypical adenomas [4, 20, 24, 32, 33]. Recently, the 2017 WHO classification was published [15]. The term atypical adenoma has been removed due to the low This article is part of the Topical Collection on Pituitaries * Florian Grimm Florian.Grimm@med.uni-tuebingen.de 1 Department for Neurosurgery, University Hospital Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany 2 Institute of Pathology and Neuropathology, Department of Neuropathology, University Hospital Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany 3 Department for Neuroradiology, University Hospital Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany Acta Neurochirurgica https://doi.org/10.1007/s00701-019-03879-4