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

Mark J Wilsher; Thomas W Owens; Richard Jn Allcock

doi:10.1002/cjp2.68

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

J Pathol Clin Res. 2017 Mar 20;3(2):115-122. doi: 10.1002/cjp2.68. eCollection 2017 Apr.

Authors

Mark J Wilsher¹, Thomas W Owens², Richard Jn Allcock^{3

4}

Affiliations

¹ Douglass Hanly Moir PathologyMacquarie ParkNew South Wales 2113Australia.
² Discipline of Physiology, School of Medical Sciences & Bosch InstituteThe University of SydneyCamperdownNew South WalesAustralia.
³ School of Pathology and Laboratory MedicineUniversity of Western AustraliaNedlandsWestern Australia6009, Australia.
⁴ Pathwest Laboratory Medicine WAQEII Medical CentreNedlandsWestern Australia6009, Australia.

PMID: 28451460
PMCID: PMC5402177
DOI: 10.1002/cjp2.68

Abstract

We sought to determine if adenosquamous proliferation of early cellular radial sclerosing lesions of the breast harbours hot spot mutations and to help clarify its relationship to low-grade adenosquamous carcinoma as a potential form of early neoplasia. Four low-grade adenosquamous carcinomas, early radial sclerosing lesions from 13 individuals, and 4 benign proliferative breast lesions were microdissected and assessed with a 50-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 in ten (77% of) radial sclerosing lesions, in one low-grade adenosquamous carcinoma, and in usual ductal hyperplasia and apocrine adenosis. Over three 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 sclerosing lesions and low-grade adenosquamous carcinomas.

Keywords: adenosquamous proliferation; breast; complex sclerosing lesion; low‐grade adenosquamous carcinoma; next‐generation sequencing; radial scar; radial sclerosing lesion.