Ameloblastic fibrosarcoma: clinicopathological and molecular analysis of seven cases highlighting frequent BRAF and occasional NRAS mutations
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
31899815
DOI
10.1111/his.14053
Knihovny.cz E-zdroje
- Klíčová slova
- BRAF, NRAS, ameloblastic fibroma, ameloblastic fibrosarcoma, molecular pathogenesis, targeted therapy,
- MeSH
- ameloblastom genetika patologie MeSH
- dospělí MeSH
- fibrosarkom genetika patologie MeSH
- GTP-fosfohydrolasy genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové proteiny genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace MeSH
- nádory čelistí genetika patologie MeSH
- protoonkogenní proteiny B-Raf genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- BRAF protein, human MeSH Prohlížeč
- GTP-fosfohydrolasy MeSH
- membránové proteiny MeSH
- NRAS protein, human MeSH Prohlížeč
- protoonkogenní proteiny B-Raf MeSH
AIMS: Ameloblastic fibrosarcoma (AFS) is an aggressive odontogenic neoplasm featuring malignant mesenchymal stroma in addition to an ameloblastic epithelial component, and is hence considered to be the malignant counterpart of ameloblastic fibroma (AF). AFS is exceedingly rare, with <110 cases having been reported so far. Although BRAF mutations are recognised driver mutations in ameloblastoma, the molecular pathogenesis of AFS remains elusive. METHODS AND RESULTS: We herein describe seven AFSs that were analysed, for the first time, for mutations in the BRAF-NRAS pathway. The patients were four females and three males aged 23-57 years (median, 26 years). Three tumours developed after one or multiple recurrences of AF (4-20 years after initial diagnosis), two showed transition from AF-like bland areas, and two developed de novo. All patients were treated with surgery; adjuvant chemotherapy was given to one patient. At the last follow-up, five patients were alive and well (19-344 months). The remainder were lost to follow-up. Histological examination showed variable sarcomatous overgrowth with varying degrees of atypia and increased mitotic activity. The epithelial component varied greatly according to the degree of sarcomatous overgrowth. Molecular testing revealed BRAF V600E mutations in five cases and NRAS p.Gln61Lys mutation in one case. One tumour was wild-type. CONCLUSION: To our knowledge, this is the first study on BRAF/NRAS mutations in AFS. Given the activity of RAF and MEK inhibitors across different cancers harbouring V600E mutations, our data strongly suggest that all AFS cases should be genetically tested, and that targeted treatment approaches for this extremely rare sarcoma subtype should be clinically investigated.
Cancer Diagnosis and Pathology Group Kolling Institute St Leonards NSW Australia
Department of Oral Medicine and Diagnostic Science King Saud University Riyadh Saudi Arabia
Department of Pathology Charles University Faculty of Medicine in Plzen Plzen Czech Republic
Department of Pathology University Hospital Basel Basel Switzerland
Department of Translational Research School of Medicine University of Pisa Pisa Italy
Institute of Pathology University Hospital Erlangen Germany
Sydney Medical School University of Sydney St Leonards NSW Australia
Zobrazit více v PubMed
Wright JM. Odontogenic sarcomas. In El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ eds. World Health Organization classification of head and neck tumours. 4th ed. Lyon: IARC Press, 2017; 214.
El-Mofty SK. Odontogeneic carcinosarcoma. In El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ eds. World Health Organization classification of head and neck tumours. 4th ed. Lyon: IARC Press, 2017; 213.
Chrcanovic BR, Brennan PA, Rahimi S, Gomez RS. Ameloblastic fibroma and ameloblastic fibrosarcoma: a systematic review. J. Oral Pathol. Med. 2018; 47; 315-325.
Martínez Martínez M, Mosqueda-Taylor A, Carlos R, Delgado-Azañero W, de Almeida OP. Malignant odontogenic tumors: a multicentric Latin American study of 25 cases. Oral Dis. 2014; 20; 380-385.
Kurppa KJ, Catón J, Morgan PR et al. High frequency of BRAF V600E mutations in ameloblastoma. J. Pathol. 2014; 232; 492-498.
Gültekin SE, Aziz R, Heydt C et al. The landscape of genetic alterations in ameloblastomas relates to clinical features. Virchows Arch. 2018; 472; 807-814.
Bartels S, Adisa A, Aladelusi T et al. Molecular defects in BRAF wild-type ameloblastomas and craniopharyngiomas-differences in mutation profiles in epithelial-derived oropharyngeal neoplasms. Virchows Arch. 2018; 472; 1055-1059.
Toon CW, Walsh MD, Chou A et al. BRAFV600E immunohistochemistry facilitates universal screening of colorectal cancers for Lynch syndrome. Am. J. Surg. Pathol. 2013; 37; 1592-1602.
Mohsenifar Z, Behrad S, Abbas FM. Epithelial dysplasia in ameloblastic fibrosarcoma arising from recurrent ameloblastic fibroma in a 26-year-old Iranian Man. Am. J. Case Rep. 2015; 16; 548-553.
Muller S, Parker DC, Kapadia SB, Budnick SD, Barnes EL. Ameloblastic fibrosarcoma of the jaws. A clinicopathologic and DNA analysis of five cases and review of the literature with discussion of its relationship to ameloblastic fibroma. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 1995; 79; 469-477.
Brunner P, Bihl M, Jundt G, Baumhoer D, Hoeller S. BRAF p.V600E mutations are not unique to ameloblastoma and are shared by other odontogenic tumors with ameloblastic morphology. Oral Oncol. 2015; 51; e77-e78.
Brown NA, Rolland D, McHugh JB et al. Activating FGFR2-RAS-BRAF mutations in ameloblastoma. Clin. Cancer Res. 2014; 20; 5517-5526.
You Z, Xu LL, Li XF, Zhang JY, Du J, Sun LS. BRAF gene mutations in ameloblastic fibromas. Beijing Da Xue Xue Bao Yi Xue Ban 2019; 51; 4-8.
Kumar P, Surya V, Urs AB, Augustine J, Mohanty S, Gupta S. Sarcomas of the oral and maxillofacial region: analysis of 26 cases with emphasis on diagnostic challenges. Pathol. Oncol. Res. 2019; 25; 593-601.
