Weigelt, B., Geyer, F. C., Horlings, H. M., Kreike, B., Halfwerk, H., Reis-Filho, J. S. (2009) Mucinous and neuroendocrine breast carcinomas are transcriptionally distinct from invasive ductal carcinomas of no special type. MODERN PATHOLOGY, 22 (11). pp. 1401-1414. ISSN 0893-3952

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Abstract

Mucinous carcinoma is considered a distinct pathological entity. However, mucinous tumours can be divided into a least two groups: mucinous A (or paucicellular) and mucinous B (or hypercellular). Mucinous B cancers display histological features that significantly overlap with those of neuroendocrine carcinomas. We investigate using genome-wide oligonucleotide microarrays whether mucinous A, mucinous B and neuroendocrine carcinomas are entities distinct from histological grade-and molecular subtype-matched invasive ductal carcinomas of no special type. Mucinous A and B and five neuroendocrine carcinomas were of luminal A subtype, whereas one neuroendocrine tumour was of luminal B phenotype. When analysed in conjunction with grade-and molecular subtype-matched invasive ductal carcinomas, hierarchical clustering analysis showed that the majority of mucinous and neuroendocrine cancers formed a separate cluster. Significance analysis of microarrays identified 3155 genes differentially expressed between mucinous/neuroendocrine carcinomas and grade-and molecular subtype-matched invasive ductal carcinomas (false discovery rate < 0.85%), and revealed that genes associated with connective tissue/extracellular matrix were downregulated in mucinous/neuroendocrine cancers compared to invasive ductal carcinomas. When subjected to hierarchical clustering analysis separately, mucinous A cancers formed a discrete subgroup, whereas no separation was observed between mucinous B and neuroendocrine cancers. In fact, significance of microarray analysis showed no transcriptomic differences between mucinous B and neuroendocrine cancers, whereas mucinous A cancers displayed 89 up-and 26 downregulated genes when compared with mucinous B (false discovery rate < 1.15%) and 368 up-and 48 downregulated genes when compared to neuroendocrine carcinomas (false discovery rate < 1.0%). Our results provide circumstantial evidence to suggest that mucinous and neuroendocrine carcinomas are transcriptionally distinct from histological grade-and molecular subtype-matched invasive ductal carcinomas, and that luminal A breast cancers are a heterogeneous group of tumours. These findings support the contention that mucinous B and neuroendocrine carcinomas are part of a spectrum of lesions, whereas mucinous A is a discrete entity. Modern Pathology (2009) 22, 1401-1414; doi: 10.1038/modpathol.2009.112; published online 24 July 2009

Item Type:	Article
Authors (ICR Faculty only):	Reis-Filho, Jorge
All Authors:	Weigelt, B., Geyer, F. C., Horlings, H. M., Kreike, B., Halfwerk, H., Reis-Filho, J. S.
Uncontrolled Keywords:	breast cancer; histological type; microarrays; classification;ENDOPLASMIC-RETICULUM STRESS; GENOME-WIDE ASSOCIATION; ENDOCRINE DIFFERENTIATION; EXPRESSION PATTERNS; MOLECULAR PORTRAITS; MICROARRAY ANALYSIS; CELL-ADHESION; CANCER; TUMORS; IDENTIFICATION
Funding Acknowledgement:	Breakthrough Breast Cancer Centre ; NHS
Funding Text:	The authors would like to thank Kay Savage for technical assistance with the immunohistochemical stainings. FCG and JSR-F are supported by Breakthrough Breast Cancer Centre. We also acknowledge NHS funding to the NIHR Biomedical Research Centre.
Research teams:	Closed research groups > Molecular Pathology
Depositing User:	Users 10 not found.
Date Deposited:	20 Nov 2009 09:10
Last Modified:	25 Feb 2014 13:06
URI:	http://publications.icr.ac.uk/id/eprint/9041

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