Comprehensive clinicopathological and molecular analysis of primary malignant melanoma of the oesophagus.
Histopathology
; 78(2): 240-251, 2021 Jan.
Article
em En
| MEDLINE
| ID: mdl-32654197
ABSTRACT
AIMS:
This study was performed to elucidate the clinicopathological characteristics, genetic alterations and therapeutic targets of primary malignant melanoma of the oesophagus (PMME). METHODS ANDRESULTS:
The clinicopathology and molecular pathology of 13 PMME cases and 10 skin malignant melanoma (SKMM) cases were analysed with next-generation sequencing (NGS) and immunohistochemistry. The 3-year overall survival rate and the median survival time for PMME patients were 23.1% and 11.9 months, respectively. Three (23.1%) and eight (61.5%) PMME cases showed a papillary structure and lymph node metastasis, respectively. DNA and RNA hybridization capture-based NGS analysis revealed that NF1 was the most frequently mutated gene (30%) in 10 of the PMME cases. Other mutations detected in PMME included SF3B1 (20%), KRAS (10%), BRCA2 (10%), KIT (10%) and TP53 (10%) mutations. Commonly detected BRAF mutations in SKMM were not detected in PMME. Immunohistochemistry and mutation status were concordant between p53/c-Kit and TP53/KIT, respectively. Focal expression of programmed death-ligand 1 was observed in one PMME sample. The tumour mutation burden in PMME was significantly lower than that in SKMM (P = 0.030). No PMME case showed high microsatellite instability. RNA sequencing revealed a distinctive pattern with respect to RNA expression. T-cell co-stimulation differed between PMME and SKMM.CONCLUSIONS:
The RAS-mitogen-activated protein kinase pathway is one of the main pathways involved in PMME. The genetic profile of PMME was similar to that of mucosal/acral melanoma, but differed from the SKMM profile. A subset of PMMEs may contain actionable mutations. Immunotherapy seemed to be less effective for most PMMEs in this series.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oncogenes
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Neoplasias Cutâneas
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Neoplasias Esofágicas
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Melanoma
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Histopathology
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão