Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy

Santi R, Cetica V, Franchi A, Pepi M, Cesinaro A M, Miracco C, Paglierani M, De Giorgi V, Delfino C, Difonzo E M, Pimpinelli N, Bianchi S, Sardi I, Santucci M & Massi D
(2011) Histopathology 58 , 455–466
Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy Aims: Atypical vascular lesions (AVL) occurring at the site of radiotherapy represent an uncommon but well‐documented complication in the setting of breast‐conserving therapy for breast carcinoma. Although the biological behaviour of AVL has been regarded as benign, it has been suggested that AVL may represent a precursor of angiosarcoma. A better understanding of the biology of AVL is essential in order to assess appropriate patient management. The aim of the present study was to investigate alterations of tumour suppressor gene TP53 in a series of radiation‐induced AVL and angiosarcomas (AS). Methods and results: Direct sequencing analysis of the TP53 gene showed the presence of at least one variation in 10 of 12 (83.3%) AVL and in seven of eight (87.5%) AS. The most common alteration in both categories was the P72R polymorphism in exon 4. One angiosarcoma sample carried a pathogenetically relevant disruptive mutation c.592delG, a frameshift deletion in exon 6, causing a premature stop codon. Conclusions: The presence of TP53 alterations suggests that its mutational inactivation may be implicated in the pathogenesis of radiation‐associated vascular proliferations. The common mutational pathway suggested by our data supports the hypothesis that AVL and AS are biologically related entities, most probably representing the extremes of a morphological continuum.