Histone H3K36M Mutation and Trimethylation Patterns in Chondroblastoma.

BACKGROUND: Histones are essential components of chromatin and mutations in histones lead to alterations in methylation and acetylation, which play an important role in tumorigenesis. Most of the chondroblastomas harbor H3K36M mutation. With the availability of mutation specific antibody, we aimed to assess the sensitivity of this antibody and the alterations of histone methylation in a series of chondroblastoma cases.

DESIGN: Immunohistochemical stains using antibodies for H3K36M, trimethylated histones (H3K27me3 and H3K36me3), and osteoblastic marker (SATB2) were performed on 27 chondroblastomas from 27 patients. The clinical and radiological characteristics of each patient was reviewed.

RESULTS: All 27 tumors showed typical radiological and histological features of chondroblastoma with a subset of cases showing secondary aneurysmal bone cyst changes (11/27), giant cell rich foci (4/27), and matrix rich areas mimicking chondromyxoid fibroma (1/27). All except 1 case (26/27, 96%) were positive for H3K36M immunostaining (nuclear). In majority of cases staining pattern was diffuse. Immunohistochemical expression of H3K27me3 and H3K36me3 revealed heterogeneous staining pattern in all cases regardless of mutation status. None of the cases showed loss or diffuse positivity. Focal or diffuse SATB2 expression was seen in 21 out of 26 tumors (81%).

CONCLUSION: Our results demonstrate that vast majority of chondroblastomas are positive for H3K36M by immunohistochemical analysis, confirming its diagnostic value. The expression of H3K27me3 and H3K36me3 are heterogeneous in these tumors. This article is protected by copyright. All rights reserved.