Transcriptomic analysis of tubular carcinomas of the breast reveals similarities and differences with molecular subtype‐matched ductal and lobular carcinomas

Abstract

Tubular carcinoma (TC) is an uncommon special type of breast cancer characterized by an indolent clinical course. Although described as part of a spectrum of related lesions named 'low-grade breast neoplasia family' due to immunophenotypical and genetic similarities, TCs, low-grade invasive ductal carcinomas of no special type (IDC-NSTs), and classic invasive lobular carcinomas (ILCs) significantly differ in terms of histological features and clinical outcome. The aim of this study was to investigate whether pure TCs constitute an entity distinct from low-grade IDC-NSTs and from classic ILCs. To define the transcriptomic differences between TCs and IDC-NSTs and ILCs whilst minimizing the impact of histological grade and molecular subtype on their profiles, we subjected a series of grade- and molecular subtype-matched TCs and IDC-NSTs and molecular subtype-matched TCs and classic ILCs to genome-wide gene expression profiling using oligonucleotide microarrays. Unsupervised and supervised analysis revealed that TCs are similar at the transcriptomic level to grade- and molecular subtype-matched IDC-NSTs. However, subtle yet significant differences were detected and validated by quantitative reverse transcriptase-PCR, which may in part explain the reported more favourable outcome of TCs. Transcriptomic differences between TCs and molecular subtype-matched classic ILCs were more overt, predominantly due to lower expression of proliferation and cell cycle genes in TCs and down-regulation of cell adhesion/extracellular matrix-related genes in classic ILCs. Our results support the existence of a 'low-grade breast neoplasia family'; however, the transcriptomes of these lesions display small, yet important differences, which, together with their distinct biological behaviour, warrant their separation as discrete entities.