title: Search for neuro-endocrine markers (chromogranin A, synaptophysin and VGF) in breast cancers. An integrated approach using immunohistochemistry and gene expression profiling.
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.
authors.affiliation: Department of Medical Sciences, University of Turin, Via Santena 7, 10126, Turin, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Annaratone
authors.forename: Enzo
authors.initials: E
authors.lastname: Medico
authors.forename: Nelson
authors.initials: N
authors.lastname: Rangel
authors.forename: Isabella
authors.initials: I
authors.lastname: Castellano
authors.forename: Caterina
authors.initials: C
authors.lastname: Marchiò
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.forename: Gianni
authors.initials: G
authors.lastname: Bussolati
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D053379:Chromogranin A / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A; D009414:Nerve Growth Factors; D016708:Synaptophysin; C510637:VGF protein, human