Mucinous and neuroendocrine breast carcinomas are transcriptionally distinct from invasive ductal carcinomas of no special type

Mod Pathol. 2009 Nov;22(11):1401-14. doi: 10.1038/modpathol.2009.112. Epub 2009 Jul 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / genetics*
  • Adenocarcinoma, Mucinous / metabolism
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • CD56 Antigen / metabolism
  • Carcinoma, Neuroendocrine / genetics*
  • Carcinoma, Neuroendocrine / metabolism
  • Chromogranins / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genome / genetics
  • Humans
  • Immunohistochemistry
  • Oligonucleotide Array Sequence Analysis
  • Staining and Labeling
  • Synaptophysin / metabolism

Substances

  • Biomarkers, Tumor
  • CD56 Antigen
  • Chromogranins
  • Synaptophysin