Post-radiotherapy vascular lesions of the breast: immunohistochemical and molecular features of 74 cases with long-term follow-up and literature review

Histopathology. 2020 Aug;77(2):293-302. doi: 10.1111/his.14090. Epub 2020 Jul 23.

Abstract

Aims: A wide range of post-radiotherapy (RT) vascular lesions can occur, ranging from benign lymphangiomatous papules of the skin (BLAPs), to atypical vascular lesions (AVLs) and post-RT angiosarcomas (ASs). The relationship between benign and malignant post-RT breast lesions and their prognostic features are still controversial. The aims of this study were to investigate the relationship between benign and malignant mammary post-RT vascular lesions and to define post-RT AS prognostic features.

Methods and results: Seventy-four post-RT vascular lesion cases were obtained and stained with antibodies against CD34, CD31, D2-40, Ki67, and c-Myc. Mutational analysis was performed by deep sequencing for the following genes: KRAS, NRAS, HRAS, BRAF, PIK3CA, TP53, NOTCH1, PTEN, CDKN2A, EGFR, AKT1, CTNNB1, hTERT, and PTPRB. Post-RT AS cases were graded according to a previously reported breast AS grading system. AVL cases showed a low number of HRAS and hTERT mutations, whereas post-RT AS cases showed a high frequency of EGFR, TP53, HRAS and hTERT mutations. On follow-up, all BLAP and AVL patients were alive with no evidence of disease. Post-RT AS 5-year overall survival declined with the increase in grade, as follows: 85.7% for grade 1, 83.3% for grade 2, and 40.4% for grade 3.

Conclusions: Our findings confirm that BLAP and AVL have a good prognosis, and that post-RT AS prognosis is strongly related to histological grading. On molecular analysis, AVL and post-RT AS shared HRAS and hTERT mutations, suggesting a relationship between the two lesions.

Keywords: atypical vascular lesions; breast; genes; haemangiosarcoma; neoplasms.

MeSH terms

  • Adult
  • Aged
  • Breast / pathology
  • Breast Neoplasms / pathology
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Hemangiosarcoma / pathology
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Neoplasms, Radiation-Induced / pathology*
  • Oncogenes / genetics
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Radiotherapy / adverse effects*
  • Skin Neoplasms / pathology
  • Telomerase / genetics
  • Telomerase / metabolism
  • Vascular Malformations / pathology*

Substances

  • Peptide Fragments
  • GV1001 peptide
  • Telomerase
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)

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