Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes

Kristen S. Purrington, Daniel W. Visscher, Chen Wang, Drakoulis Yannoukakos, Ute Hamann, Heli Nevanlinna, Angela Cox, Graham G. Giles, Jeanette E. Eckel-Passow, Sotiris Lakis, Vassiliki Kotoula, George Fountzilas, Maria Kabisch, Thomas Rüdiger, Päivi Heikkilä, Carl Blomqvist, Simon S Cross, Melissa C. Southey, Janet E Olson, Judy GilbertSandra Deming-Halverson, Veli-Matti Kosma, Christine Clarke, Rodney Scott, J. Louise Jones, Wei Zheng, Arto Mannermaa, Carpenter for ABCTC Investigators Jane Carpenter for ABCTC Investigators, Diana M Eccles, Celine M Vachon, Fergus J Couch

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13 Citations (Scopus)

Abstract

Distinct subtypes of triple negative (TN) breast cancer have been identified by tumor expression profiling. However, little is known about the relationship between histopathologic features of TN tumors, which reflect aspects of both tumor behavior and tumor microenvironment, and molecular TN subtypes. The histopathologic features of TN tumors were assessed by central review and 593 TN tumors were subjected to whole genome expression profiling using the Illumina Whole Genome DASL array. TN molecular subtypes were defined based on gene expression data associated with histopathologic features of TN tumors. Gene expression analysis yielded signatures for four TN subtypes (basal-like, androgen receptor positive, immune, and stromal) consistent with previous studies. Expression analysis also identified genes significantly associated with the 12 histological features of TN tumors. Development of signatures using these markers of histopathological features resulted in six distinct TN subtype signatures, including an additional basal-like and stromal signature. The additional basal-like subtype was distinguished by elevated expression of cell motility and glucose metabolism genes and reduced expression of immune signaling genes, whereas the additional stromal subtype was distinguished by elevated expression of immunomodulatory pathway genes. Histopathologic features that reflect heterogeneity in tumor architecture, cell structure, and tumor microenvironment are related to TN subtype. Accounting for histopathologic features in the development of gene expression signatures, six major subtypes of TN breast cancer were identified.

Original languageEnglish
Pages (from-to)117-131
Number of pages15
JournalBreast Cancer Research and Treatment
Volume157
Issue number1
DOIs
Publication statusPublished - 1 May 2016
Externally publishedYes

Keywords

  • Breast cancer
  • Gene expression
  • Germline mutation
  • Pathology
  • Tumor biology

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