Abstract
Discordant data are reported in the literature on the definition, incidence and clinical features of neuroendocrine (NE) carcinomas of the breast. This tumour entity is currently assessed by immunohistochemistry (IHC) detecting “general” NE markers such as chromogranin A (CHGA) and synaptophysin (SYP), but other markers have been considered as well. In the present study, in addition to CHGA and SYP, we investigated the expression of VGF, a neurotrophin-inducible gene, which is emerging as a new specific NE marker. In order to evaluate the differential expression of these neuro-endocrine markers in breast cancers, we conducted parallel immunohistochemical and gene expression analyses, using PCR, gene array and real-time quantitative PCR procedures. Data obtained in 28 cases were further validated with a meta-analysis of published datasets of 103 breast cancer cases. The value of IHC positivity (irrespective of the percentage of positive cells) was confirmed by over-expression of the related gene. However, the genetic approach emerged as more sensitive, showing over-expression of NE markers in a subset of IHC-negative carcinomas. In conclusion, the present study confirms, by a novel approach, the occurrence of NE differentiation in breast cancers. Over-expression of one or more NE marker (CHGA and/or SYP and/or VGF) characterizes a significant fraction (approximately 10 %) of infiltrative breast cancers.Electronic supplementary materialThe online version of this article (doi:10.1007/s12022-013-9277-4) contains supplementary material, which is available to authorized users.
Highlights
The reported incidence of neuroendocrine (NE) differentiation in invasive breast carcinomas (IBC) is variable from 2 up to 20 %, depending on the criteria and detection methods [1,2,3]
To validate our results in a large cohort of breast cancer patients, we focused on a published gene expression dataset obtained using Affymetrix DNA microarrays on 103 biopsies of aggressive breast carcinomas that were subjected to neoadjuvant treatment [18]
In case 3, which was negative for chromogranin A (CHGA) in IHC, gene expression for this NE marker was 35, 000-fold down-regulated as compared to cases 1 and 2 (Table 1)
Summary
The reported incidence of neuroendocrine (NE) differentiation in invasive breast carcinomas (IBC) is variable from 2 up to 20 %, depending on the criteria and detection methods [1,2,3]. In the 2012 revised WHO classification, the NEC definition included three categories: (1) NEC, well-differentiated (carcinoid-like pattern), (2) NEC, poorly differentiated/small cell carcinoma and (3) IBC with NE differentiation determined by immunohistochemistry (IHC) [5]. All of these tumours should express NE markers to a greater or a lesser degree and in this WHO classification the minimum quantity
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