title: Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Division of Pathological Anatomy, Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy. raffaella.santi@yahoo.it
authors.forename: Raffaella
authors.initials: R
authors.lastname: Santi
authors.forename: Valentina
authors.initials: V
authors.lastname: Cetica
authors.forename: Alessandro
authors.initials: A
authors.lastname: Franchi
authors.forename: Monica
authors.initials: M
authors.lastname: Pepi
authors.forename: Anna M
authors.initials: AM
authors.lastname: Cesinaro
authors.forename: Clelia
authors.initials: C
authors.lastname: Miracco
authors.forename: Milena
authors.initials: M
authors.lastname: Paglierani
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Giorgi
authors.forename: Chiara
authors.initials: C
authors.lastname: Delfino
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Difonzo
authors.forename: Nicola
authors.initials: N
authors.lastname: Pimpinelli
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bianchi
authors.forename: Iacopo
authors.initials: I
authors.lastname: Sardi
authors.forename: Marco
authors.initials: M
authors.lastname: Santucci
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000150:complications / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006394:Hemangiosarcoma / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D012867:Skin / Q000098:blood supply / Q000473:pathology*; D014652:Vascular Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology