Next generation sequencing of the nidus of early (adenosquamous proliferation rich) radial sclerosing lesions of the breast reveals evidence for a neoplastic precursor lesion

We sought to determine if adenosquamousproliferation of early cellular radial sclerosing lesions of the breast harbours hot spot mutations and to help clarify its relationship to low-gradeadenosquamous carcinoma as a potential form of early neoplasia.Four low-gradeadenosquamous carcinomas, early radial sclerosing lesions from 13 individuals, and 4benign proliferative breast lesions were microdissectedand assessed with a50-gene Hot-spot cancer panel.Early radial sclerosing lesions were selectively microdissected concentrating on their adenosquamous proliferation (nidus). Hot spot mutations in PIK3CA were detected inten(77% of) radial sclerosing lesions, in one low-gradeadenosquamous carcinoma, and in usual ductal hyperplasia and apocrine adenosis.Overthree quarters of individuals with cellular (adenosquamous proliferation rich) early radial sclerosing lesions tested harboured somatic mutations in PIK3CA suggesting that adenosquamous proliferation is a clonal lesion. Its relationship to low grade adenosquamous carcinoma remains unclear in view of the small sample size and unmatched radial scar lesions and low-grade adenosquamous carcinomas. This article is protected by copyright. All rights reserved.