title: Human achaete-scute homolog-1 expression in neuroendocrine breast carcinoma.
abstract: Neuroendocrine (NE) breast carcinoma is defined by morphological features similar to those of NE tumors of other organs and NE marker expression in at least 50 % of neoplastic cells. However, a NE morphology may be observed even in breast carcinomas lacking NE markers. Human achaete-scute homolog-1 (hASH-1) is a transcription factor that plays a key role in the regulation of mammalian neural and NE cell development and has been identified in several human NE tumors. The aim of this study was to investigate hASH-1 expression in human breast cancers. hASH-1 expression was evaluated in 482 consecutive non-NE invasive breast carcinomas, in a series of 84 breast cancers with >50 % NE marker expression (high NE differentiation) and 21 carcinomas with NE histology but negative or focally (<50 %) positive for NE markers (low NE differentiation). hASH-1 protein was evaluated by a specific monoclonal antibody using immunohistochemistry and gene expression by real-time polymerase chain reaction. None of the non-NE invasive breast carcinomas expressed hASH-1 at any levels. hASH-1 was expressed in tumor cell nuclei of 63 and 38 % of cases with high and low NE differentiation, respectively. Strong correlation with protein and gene expression levels was observed (p < 0.0001). hASH-1 expression was correlated to a low mitotic count (p = 0.02) and a low Ki67 proliferative index (p = 0.0062). hASH-1 expression occurs in breast cancers with NE differentiation regardless of the extent of the NE cell population, and it is restricted to a subset of tumor cells having a low proliferative potential.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin at San Luigi Hospital, Orbassano, Turin, Italy. luisella.righi@unito.it
authors.forename: Luisella
authors.initials: L
authors.lastname: Righi
authors.forename: Ida
authors.initials: I
authors.lastname: Rapa
authors.forename: Arianna
authors.initials: A
authors.lastname: Votta
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; C065500:ASCL1 protein, human