These authors contributed equally to this work.
Article first published online: 14 JUL 2008
Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 216, Issue 2, pages 141–150, October 2008
How to Cite
Weigelt, B., Horlings, H., Kreike, B., Hayes, M., Hauptmann, M., Wessels, L., de Jong, D., Van de Vijver, M., Veer, L. V. and Peterse, J. (2008), Refinement of breast cancer classification by molecular characterization of histological special types. J. Pathol., 216: 141–150. doi: 10.1002/path.2407
This article is dedicated to the memory of Dr Hans Peterse.
Conflicts of interest: LJ Van't Veer is an employee of, and holds shares in, Agendia. BV.
- Issue published online: 2 SEP 2008
- Article first published online: 14 JUL 2008
- Accepted manuscript online: 14 JUL 2008 12:00AM EST
- Manuscript Accepted: 2 JUL 2008
- Manuscript Revised: 1 JUL 2008
- Manuscript Received: 20 APR 2008
- Dutch Cancer Society. Grant Number: (KWF 02-2575)
- Cancer Genomics Center (Netherlands Genomics Initiative)
- breast cancer;
- expression profiling;
- histological classification;
- molecular subtypes
Most invasive breast cancers are classified as invasive ductal carcinoma not otherwise specified (IDC NOS), whereas about 25% are defined as histological ‘special types’. These special-type breast cancers are categorized into at least 17 discrete pathological entities; however, whether these also constitute discrete molecular entities remains to be determined. Current therapy decision-making is increasingly governed by the molecular classification of breast cancer (luminal, basal-like, HER2+). The molecular classification is derived from mainly IDC NOS and it is unknown whether this classification applies to all histological subtypes. We aimed to refine the breast cancer classification systems by analysing a series of 11 histological special types [invasive lobular carcinoma (ILC), tubular, mucinous A, mucinous B, neuroendocrine, apocrine, IDC with osteoclastic giant cells, micropapillary, adenoid cystic, metaplastic, and medullary carcinoma] using immunohistochemistry and genome-wide gene expression profiling. Hierarchical clustering analysis confirmed that some histological special types constitute discrete entities, such as micropapillary carcinoma, but also revealed that others, including tubular and lobular carcinoma, are very similar at the transcriptome level. When classified by expression profiling, IDC NOS and ILC contain all molecular breast cancer types (ie luminal, basal-like, HER2+), whereas histological special-type cancers, apart from apocrine carcinoma, are homogeneous and only belong to one molecular subtype. Our analysis also revealed that some special types associated with a good prognosis, such as medullary and adenoid cystic carcinomas, display a poor prognosis basal-like transcriptome, providing strong circumstantial evidence that basal-like cancers constitute a heterogeneous group. Taken together, our results imply that the correct classification of breast cancers of special histological type will allow a more accurate prognostication of breast cancer patients and facilitate the identification of optimal therapeutic strategies. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.