Histological and immunohistochemical features and genetic alterations in the malignant progression of giant cell tumor of bone: a possible association with TP53 mutation and loss of H3K27 trimethylation
| Autor: | Makoto Endo, Hidetaka Yamamoto, Shin Ishihara, Kengo Kawaguchi, Yoshihiro Matsumoto, Yuichi Yamada, Yasuharu Nakashima, Kenichi Kohashi, Yoshihiro Ito, Toshifumi Fujiwara, Izumi Kinoshita, Yuko Kakuda, Yousuke Susuki, Takeo Yamamoto, Nokitaka Setsu, Masato Yoshimoto, Yoshinao Oda, Yu Toda, Takeshi Iwasaki |
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| Rok vydání: | 2022 |
| Předmět: |
Giant Cell Tumor of Bone
Pathology medicine.medical_specialty medicine.diagnostic_test EZH2 Bone Neoplasms Sarcoma Biology medicine.disease Methylation Pathology and Forensic Medicine Malignant transformation Histones Histone Mutation Histone methylation medicine biology.protein Humans Immunohistochemistry Tumor Suppressor Protein p53 Gene In Situ Hybridization Fluorescence Fluorescence in situ hybridization Giant-cell tumor of bone |
| Zdroj: | Modern Pathology. 35:640-648 |
| ISSN: | 0893-3952 |
| DOI: | 10.1038/s41379-021-00972-x |
| Popis: | In rare cases, giant cell tumor of bone (GCTB) can undergo primary or secondary malignant transformation to malignant giant cell tumor of bone (MGCTB), but the details of the molecular alterations are still unclear. The present study aimed to elucidate the clinicopathologic and molecular features of MGCTBs based on immunohistochemistry, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) of nine MGCTBs (five primary and four secondary). Seven (78%) of 9 MGCTBs were immunohistochemically positive for H3.3 G34W. In two (22%) patients, although GCTB components were focally or diffusely positive for H3.3 G34W, their malignant components were entirely negative for H3.3 G34W, which was associated with heterozygous loss of H3F3A by FISH. NGS on four MGCTBs revealed pathogenic mutations in TP53 (n = 3), EZH2 (n = 1) and several other genes. Immunohistochemical analysis of the nine MGCTBs confirmed the p53 nuclear accumulation (n = 5) and loss of H3K27me3 expression (n = 3) and showed that they were mutually exclusive. In addition, four (80%) of five cases of pleomorphic or epithelioid cell-predominant MGCTBs were positive for p53, while three (75%) of four cases of spindle cell-predominant MGCTBs were negative for trimethylation at lysine 27 of histone 3 (H3K27me3). The results suggested that p53 alteration and dysfunction of histone methylation as evidenced by H3K27me3 loss may play an important role in the malignant progression of GCTB, and might contribute to the phenotype-genotype correlation in MGCTB. The combined histologic, immunohistochemical and molecular information may be helpful in part for the diagnosis of challenging cases. |
| Databáze: | OpenAIRE |
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