Open Access

Mirko Hladik, Isabella Nasi-Kordhishti, Jens Schittenhelm, Benjamin Bender, Marcos Tatagiba, Jürgen Honegger, Felix Behling

• Background: Pituitary adenomas are one of the most common intracranial tumors and are usually benign. However, pituitary adenomas tend to show invasive growth and some of them show aggressive behavior with resistance to standard therapies. It is therefore of clinical importance to identify such cases in order to adjust the further clinical management. A prognostic impact of alterations of the histone trimethylation of H3K have been described and osteonectin has been identified as a marker of invasive growth in several other tumor entities. Methods: We analyzed tumor tissue samples of 927 pituitary adenomas, resected between October 2004 and April 2018 in the authors’ institution. Tissue microarrays were constructed and immunohistochemical staining for H3K27me3, H3K36me3 and osteonectin was done and a semiquantitative scoring system applied. Immunohistochemical expression of MIB-1 was quantified digitally using representative images of routine stainings. Clinical data includingBackground: Pituitary adenomas are one of the most common intracranial tumors and are usually benign. However, pituitary adenomas tend to show invasive growth and some of them show aggressive behavior with resistance to standard therapies. It is therefore of clinical importance to identify such cases in order to adjust the further clinical management. A prognostic impact of alterations of the histone trimethylation of H3K have been described and osteonectin has been identified as a marker of invasive growth in several other tumor entities. Methods: We analyzed tumor tissue samples of 927 pituitary adenomas, resected between October 2004 and April 2018 in the authors’ institution. Tissue microarrays were constructed and immunohistochemical staining for H3K27me3, H3K36me3 and osteonectin was done and a semiquantitative scoring system applied. Immunohistochemical expression of MIB-1 was quantified digitally using representative images of routine stainings. Clinical data including recurrence-free survival according to radiographic follow-up images was collected. Invasive tumor growth was assessed retrospectively based on surgical reports. Results: The rate of invasive growth according to surgical reports was 42.61% (395 of 927 cases). The overall recurrence rate was 20.14% (175 of 869 cases with available follow-up data) with a mean follow-up of 2.64 years, ranging from 0.06 to 15.20 years. A MIB-1 expression ≥0.6% was associated with a higher rate of invasive growth and a shorter recurrence-free survival in the univariate (p=0.0320 and p=0.0135, respectively) and the multivariate analysis (p=0.0222, odds ratio=1.44 and p=0.0408, hazards ratio=1.58, respectively). Loss of H3K27me3 showed a higher rate of invasive growth in the univariate and the multivariate analysis (p=0.0312 and p=0.0305, odds ratio=2.68, respectively). There was no significant impact of H3K36me3 or osteonectin regarding invasive growth and recurrence-free survival. Conclusions: MIB-1 expression and loss of H3K27me3 were independent markers for invasive tumor growth but only MIB-1 showed an independent prognostic impact.…