The histopathological evaluation of
morphological features in breast tu
mours provides prognostic infor
mation to guide therapy. Adjunct
molecular analyses provide further diagnostic, prognostic and predictive infor
mation. However, there is li
mited knowledge of the
molecular basis of
morphological phenotypes in invasive breast cancer. This study integrated geno
mic, transcripto
mic and protein data to provide a co
mprehensive
molecular profiling of
morphological features in breast cancer. Fifteen pathologists assessed 850 invasive breast cancer cases fro
m The Cancer Geno
me Atlas (TCGA). Morphological features were significantly associated with geno
mic alteration, DNA
methylation subtype, PAM50 and
microRNA subtypes, proliferation scores, gene expression and/or reverse-phase protein assay subtype. Marked nuclear pleo
morphis
m, necrosis, infla
mmation and a high
mitotic count were associated with the basal-like subtype, and had a si
milar
molecular basis. O
mics-based signatures were constructed to predict
morphological features. The association of
morphology transcripto
me signatures with overall survival in oestrogen receptor (ER)-positive and ER-negative breast cancer was first assessed by use of the Molecular Taxono
my of Breast Cancer International Consortiu
m (METABRIC) dataset; signatures that re
mained prognostic in the METABRIC
multivariate analysis were further evaluated in five additional datasets. The transcripto
mic signature of poorly differentiated epithelial tubules was prognostic in ER-positive breast cancer. No signature was prognostic in ER-negative breast cancer. This study provided new insights into the
molecular basis of breast cancer
morphological phenotypes. The integration of
morphological with
molecular data has the potential to refine breast cancer classification, predict response to therapy, enhance our understanding of breast cancer biology, and i
mprove clinical
manage
ment. This work is publicly accessible at
www.dx.ai/tcga_breast. Copyright