Division of Pathological Anatomy, Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy.
Histopathology. 2011 Feb;58(3):455-66. doi: 10.1111/j.1365-2559.2011.03770.x. Epub 2011 Feb 16.
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).
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.
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.
在乳腺癌保乳治疗中，放射治疗部位出现的非典型血管病变（AVL）是一种罕见但已有充分记录的并发症。尽管 AVL 的生物学行为被认为是良性的，但有人认为 AVL 可能是血管肉瘤的前兆。为了评估适当的患者管理，了解 AVL 的生物学特性至关重要。本研究的目的是研究一系列放射诱导的 AVL 和血管肉瘤（AS）中肿瘤抑制基因 TP53 的改变。
直接测序分析 TP53 基因显示，在 12 个 AVL 中有 10 个（83.3%）和 8 个 AS 中有 7 个（87.5%）至少存在一个变异。这两类中最常见的改变是外显子 4 中的 P72R 多态性。一个血管肉瘤样本携带了一个致病相关的破坏性突变 c.592delG，这是外显子 6 中的一个移码缺失，导致提前出现终止密码子。
TP53 改变的存在表明其突变失活可能与放射相关血管增殖的发病机制有关。我们的数据提示的常见突变途径支持这样一种假设，即 AVL 和 AS 是生物学上相关的实体，最有可能代表形态连续体的极端。
