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

Division of Experimental Therapy, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
Modern Pathology (Impact Factor: 6.19). 07/2009; 22(11):1401-14. DOI: 10.1038/modpathol.2009.112
Source: PubMed


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.

Download full-text


Available from: Felipe C Geyer
  • Source
    • "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: 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.
    Full-text · Article · Jun 2014 · Molecular Oncology
  • Source
    • "This classification has since then been shown to be of prognostic [5] and predictive [6] value with luminal A carcinomas showing the best prognosis. It is now known that some histologic special types of invasive breast carcinoma cluster to mainly one molecular subtype: Weigelt et al. showed that cellular invasive mucinous carcinoma and neuroendocrine carcinomas mostly represent the luminal A molecular subtype [7]. "
    [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.
    Full-text · Article · Feb 2014
  • Source
    • "Until now, only a few cases of neuroendocrine carcinoma with a mucinous carcinoma component within the same tumor have been reported in the female breast (17,18), although this type of tumor has not been documented yet in the male breast. This phenomenon is suggested to represent the same genetic background present in both type B mucinous carcinoma and neuroendocrine carcinoma of the breast, since Weigelt et al clearly revealed that no differences in gene expression were present in these two types of tumors using genome-wide oligonucleotide microarrays (19). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Male breast carcinoma is an uncommon neoplasm, accounting for 0.6% of all breast carcinomas. Invasive ductal carcinoma of no special type is the most common type of male breast carcinoma, and mucinous carcinoma occurring in the male breast is extremely rare. In the present study, we report a case of mucinous carcinoma of the male breast and discuss the clinicopathological features of this type of tumor. A 63-year-old Japanese male presented with a gradually enlarged nodule in the right breast. The resected breast specimen revealed pure mucinous carcinoma and immunohistochemical analyses demonstrated that tumor cells were positive for estrogen receptor (ER), but negative for progesterone receptor (PgR). In addition, HER2 expression was not amplified. Pure mucinous carcinoma is generally associated with a low incidence of lymph node or distant metastases, and excellent disease-free survival in females. However, certain cases of this type of tumor with axillary lymph node metastasis in the male breast have been reported. In addition, the immunoprofiles of mucinous carcinoma in males are fundamentally the same as those in females. More than 90% of cases show positive immunoreactivity for ER and/or PgR, and HER2 expression is not amplified. However, it has been reported that breast cancer in males is more frequently positive for ER than in females, and has less HER2 overexpression. The high rate of hormone receptor-positive breast cancer in males is considered to be due to similar conditions as those in breast cancer in postmenopausal women. The pathogenesis of male breast carcinoma, including mucinous carcinoma, remains unclear; therefore, additional clinicopathological studies are required.
    Full-text · Article · Feb 2014 · Oncology letters
Show more