Mucinous and neuroendocrine breast carcinomas are transcriptionally distinct from invasive ductal carcinomas of no special type
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.
Get notified about updates to this publicationFollow publication
[Show abstract] [Hide abstract] ABSTRACT: Background Pure mucinous adenocarcinoma of the breast is a rare entity characterized by the production of variable amounts of mucin comprising 1% to 6% of breast carcinomas. Some mucinous adenocarcinomas have shown expression of intestinal differentiation markers such as MUC-2. This study examines the expression of intestinal differentiation markers in this type of breast carcinoma. Results Twenty-two cases of pure mucinous adenocarcinoma of the breast were assessed. Immunochemistry was performed for beta-catenin, CDX-2 and MUC-2. All cases were positive for B-catenin. MUC-2 positivity was observed in all cases; 63. 6% were 3 plus positive. All cases were negative for CDX-2. Conclusions These results suggest that mucinous breast carcinomas express some markers of intestinal differentiation, such as MUC-2 and beta-catenin; however, future studies with a larger series of cases and using molecular techniques that help affirm these results are needed.0Comments 0Citations
- "Lacroix- Triki et al.  found less genetic instability, suggesting that it is not only a histological entity, but also molecularly distinct from common ductal adenocarcinoma. Others studies, especially those from the late nineties, present the neuroendocrine differentiation of these neoplasms, which can occur in a variable percentage from 21% to 42% with histochemical studies, immunohistochemistry, and ultra- strcture181920. The importance of this variety of breast adenocarcinoma is that numerous studies have shown that PMACB has a better prognosis than mixed or common ductal types [4,5]. Volkan Adsay et al.  propose that secretion of distinct mucin, specifically to the stromal surface, acts as a container for neoplastic cells, reducing their ability to disseminate. "
[Show abstract] [Hide abstract] ABSTRACT: Integrative genomic and transcriptomic characterization of papillary carcinomas of the breast, Molecular Oncology (2014), doi: 10.1016/j.molonc.2014.06.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.0Comments 9Citations
- "c ana - lyses of special histologic types of breast cancer conducted by our group and others ( Bertucci et al . , 2008 ; Duprez et al . , 2012 ; Geyer et al . , 2010 ; Gruel et al . , 2010 ; Horlings et al . , 2013 ; Lacroix - Triki et al . , 2010 ; Lopez - Garcia et al . , 2010b ; Marchio et al . , 2009 , 2008 ; Vincent - Salomon et al . , 2007 ; Weigelt et al . , 2009a , 2010b , 2008 , 2009b ; Wetterskog et al . , 2012 ) have demonstrated that tumors from each of the special histologic types of breast cancer are more homogeneous amongst them - selves than IDC - NSTs . In addition , some of the histologic spe - cial types have been shown to be driven by recurrent fusion genes resultant of chromosomal t"
[Show abstract] [Hide abstract] ABSTRACT: Background: Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic) luminal A subtype. Methods: We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin). Results: We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A). In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior. Conclusions: We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies.0Comments 1Citation
- "This underlines the need to specify the subtype and grade of neuroendocrine tumor as accurately as possible. As cellular invasive mucinous carcinomas (with low-grade morphology) clusters in the luminal A molecular subgroup  and solid papillary carcinoma is considered to mostly represent an intraductal carcinoma with possible associated invasive carcinoma , these tumors obviously represent low-grade carcinomas with a very good prognosis. On the other hand small cell carcinoma of the breast is a neuroendocrine carcinoma of high-grade, although in a recent study it has been shown to be less aggressive than, for example, small cell carcinoma of the lung . "