Loss of H3K27me3 expression in canine nerve sheath tumors

Kristina Tekavec; Tanja Švara; Tanja Knific; Jernej Mlakar; Mitja Gombač; Carlo Cantile

doi:10.3389/fvets.2022.921720

Loss of H3K27me3 expression in canine nerve sheath tumors

Front Vet Sci. 2022 Jul 29:9:921720. doi: 10.3389/fvets.2022.921720. eCollection 2022.

Authors

Kristina Tekavec^{1

2}, Tanja Švara², Tanja Knific³, Jernej Mlakar⁴, Mitja Gombač², Carlo Cantile¹

Affiliations

¹ Department of Veterinary Science, University of Pisa, Pisa, Italy.
² Veterinary Faculty, Institute of Pathology, Wild Animals, Fish and Bees, University of Ljubljana, Ljubljana, Slovenia.
³ Veterinary Faculty, Institute of Food Safety, Feed and Environment, University of Ljubljana, Ljubljana, Slovenia.
⁴ Faculty of Medicine, Institute of Pathology, University of Ljubljana, Ljubljana, Slovenia.

Abstract

Nerve sheath tumors (NSTs) are characterized by neoplastic proliferation of Schwann cells, perineurial cells, endoneurial and/or epineurial fibroblasts. Diagnosis of NST is often challenging, particularly in distinguishing malignant NST (MNST) from other soft tissue sarcomas, or sometimes between low-grade MNST and benign NST. Recent studies in human pathology have demonstrated loss of trimethylation at lysine 27 of histone 3 (H3K27me3) in a subset of MNSTs using immunohistochemistry. Loss of H3K27me3 expression is rare in other high-grade sarcomas and also appears to be useful in distinguishing benign and low-grade MNSTs from high-grade subsets. In our retrospective study, we performed H3K27me3 immunohistochemistry in 68 canine tumors previously diagnosed as NST. We detected loss of H3K27me3 expression in 25% (n = 17) of all canine NST, including one neurofibroma, whereas 49% (n = 33) of tumors had mosaic loss of expression and 26% (n = 18) retained expression. No statistically significant differences were found between H3K27me3 expression, histopathological features of tumors, and their immunoreactivity for Sox10, claudin-1, GFAP, and Ki67. Because the classification of canine NST is not yet fully established and its correlation with the prognosis and clinical course of the disease is lacking, prospective studies with possible genetic analyses are needed to assess the true diagnostic value of H3K27me3 loss in canine NST.

Keywords: H3K27me3; dog; immunohistochemistry; methylation; nerve sheath tumor.