TY - JOUR
T1 - Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes
AU - Purrington, Kristen S.
AU - Visscher, Daniel W.
AU - Wang, Chen
AU - Yannoukakos, Drakoulis
AU - Hamann, Ute
AU - Nevanlinna, Heli
AU - Cox, Angela
AU - Giles, Graham G.
AU - Eckel-Passow, Jeanette E.
AU - Lakis, Sotiris
AU - Kotoula, Vassiliki
AU - Fountzilas, George
AU - Kabisch, Maria
AU - Rüdiger, Thomas
AU - Heikkilä, Päivi
AU - Blomqvist, Carl
AU - Cross, Simon S
AU - Southey, Melissa C.
AU - Olson, Janet E
AU - Gilbert, Judy
AU - Deming-Halverson, Sandra
AU - Kosma, Veli-Matti
AU - Clarke, Christine
AU - Scott, Rodney
AU - Jones, J. Louise
AU - Zheng, Wei
AU - Mannermaa, Arto
AU - Carpenter, Jane E.
AU - Jane Carpenter for ABCTC Investigators
AU - Eccles, Diana M
AU - Vachon, Celine M
AU - Couch, Fergus J
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Gene expression
KW - Germline mutation
KW - Pathology
KW - Tumor biology
UR - http://www.scopus.com/inward/record.url?scp=84963760752&partnerID=8YFLogxK
U2 - 10.1007/s10549-016-3775-2
DO - 10.1007/s10549-016-3775-2
M3 - Article
AN - SCOPUS:84963760752
SN - 0167-6806
VL - 157
SP - 117
EP - 131
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -
