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

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

Abstract

Introduction

A wide range of post‐radiotherapy vascular lesions can occur, ranging from Benign lymph‐angiomatous papule of the skin (BLAP), to Atypical vascular Lesions (AVL) and post‐RT angiosarcomas (Post‐RT AS). The relationship between benign and malignant post‐RT breast lesions and their prognostic features is still controversial.

Aim of the study

is to investigate the relationship between benign and malignant mammary post‐RT vascular lesions and to define post‐RT AS prognostic features.

Materials and methods

Seventy four cases of post‐RT vascular lesions were obtained and stained with antibodies against CD 34, CD 31, 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, PTPRB. Post‐RT AS were graded according to a previously reported breast AS grading system.

Results

AVL cases showed a low number of mutations in HRAS and hTERT, while post‐RT AS showed a high mutation frequency for EGFR, TP53, HRAS, and hTERT. On follow‐up, all BLAP and AVL were alive with no evidence of disease. Post‐RT AS 5‐years overall survival declined with the increase of grade as follows: 85.7% in G1, 83.3% in G2 and 40.4% in G3.

Conclusions

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