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

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Purrington , K S , Visscher , D W , Wang , C , Yannoukakos , D , Hamann , U , Nevanlinna , H , Cox , A , Giles , G G , Eckel-Passow , J E , Lakis , S , Kotoula , V , Fountzilas , G , Kabisch , M , Ruediger , T , Heikkila , P , Blomqvist , C , Cross , S S , Southey , M C , Olson , J E , Gilbert , J , Deming-Halverson , S , Kosma , V-M , Clarke , C , Scott , R , Jones , J L , Zheng , W , Mannermaa , A , Eccles , D M , Vachon , C M , Couch , F J & Jane Carpenter ABCTC Investigators 2016 , ' Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes ' , Breast Cancer Research and Treatment , vol. 157 , no. 1 , pp. 117-131 .

Title: Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes
Author: Purrington, Kristen S.; Visscher, Daniel W.; Wang, Chen; Yannoukakos, Drakoulis; Hamann, Ute; Nevanlinna, Heli; Cox, Angela; Giles, Graham G.; Eckel-Passow, Jeanette E.; Lakis, Sotiris; Kotoula, Vassiliki; Fountzilas, George; Kabisch, Maria; Ruediger, Thomas; Heikkila, Paivi; Blomqvist, Carl; Cross, Simon S.; Southey, Melissa C.; Olson, Janet E.; Gilbert, Judy; Deming-Halverson, Sandra; Kosma, Veli-Matti; Clarke, Christine; Scott, Rodney; Jones, J. Louise; Zheng, Wei; Mannermaa, Arto; Eccles, Diana M.; Vachon, Celine M.; Couch, Fergus J.; Jane Carpenter ABCTC Investigators
Contributor organization: Department of Obstetrics and Gynecology
Department of Pathology
Department of Oncology
Date: 2016-05
Language: eng
Number of pages: 15
Belongs to series: Breast Cancer Research and Treatment
ISSN: 0167-6806
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.
Subject: Gene expression
Tumor biology
Germline mutation
Breast cancer
3122 Cancers
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion

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