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Clinicopathological analysis of ATRX , DAXX and NOTCH receptor expression in angiosarcomas
Author(s) -
Panse Gauri,
Chrisinger John SA,
Leung Cheuk H,
Ingram Davis R,
Khan Samia,
Wani Khalida,
Lin Heather,
Lazar Alexander J,
Wang WeiLien
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13337
Subject(s) - death associated protein 6 , atrx , angiosarcoma , notch signaling pathway , pathology , biology , cancer research , medicine , receptor , nuclear protein , gene , genetics , mutation , transcription factor
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 ( NOTCH 1 and NOTCH 2) in a large cohort of angiosarcomas, and study their clinicopathological and prognostic significance. Methods and results One hundred and forty cases of angiosarcoma were stained for ATRX , DAXX , NOTCH 1 and NOTCH 2. 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 NOTCH 1 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). NOTCH 2 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 , NOTCH 1 and NOTCH 2 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.