Clinicopathological analysis of ATRX, DAXX and NOTCH receptor expression in angiosarcomas.
Histopathology
; 72(2): 239-247, 2018 Jan.
Article
en En
| MEDLINE
| ID: mdl-28796347
ABSTRACT
AIMS:
Multiple genetic alterations, including alternative lengthening of telomeres (ALT) and NOTCH mutations, have been described in angiosarcoma. Loss of α-thalassaemia/mental retardation syndrome X-linked (ATRX) and death domain-associated protein 6 (DAXX) expression is frequently associated with the ALT phenotype. Additionally, inhibition of NOTCH signalling induces the development of malignant vascular tumours in mice, indicating a tumour suppressive role of the NOTCH pathway in the pathogenesis of angiosarcoma. The aim of this study was to evaluate the immunohistochemical expression of ATRX, DAXX and NOTCH receptors (NOTCH1 and NOTCH2) in a large cohort of angiosarcomas, and study their clinicopathological and prognostic significance. METHODS ANDRESULTS:
One hundred and forty cases of angiosarcoma were stained for ATRX, DAXX, NOTCH1 and NOTCH2. ATRX loss (<10% labelling) was seen in seven of 118 (6%) cases, and was more frequent in deep soft tissue tumours than in other body sites (P = 0.004). Angiosarcomas with ATRX loss were associated with worse event-free survival than angiosarcomas with retained ATRX expression (P = 0.003). DAXX was retained in all specimens examined. Decreased NOTCH1 expression (≤1+ intensity) was seen in 29 of 123 (24%) cases, and was associated with a cutaneous site of origin (P = 0.013) and advanced disease (P = 0.026). NOTCH2 expression was decreased in 16 of 103 (16%) cases, was associated with visceral tumours (P = 0.001), and correlated with worse disease-specific survival (P = 0.033).CONCLUSIONS:
ATRX, NOTCH1 and NOTCH2 expression varies in angiosarcomas and shows significant correlations with site of origin and poor clinical outcome, thus highlighting the biological heterogeneity within this tumour type.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
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Biomarcadores de Tumor
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Proteínas Adaptadoras Transductoras de Señales
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Receptores Notch
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Proteína Nuclear Ligada al Cromosoma X
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Hemangiosarcoma
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Histopathology
Año:
2018
Tipo del documento:
Article