NOTCH-1 is a trans-membrane receptor protein. Ligand proteins expressed on the surface of neighbouring cells bind to the NOTCH-1 extracellular domain by juxtacrine signaling and release the NOTCH-intracellular-domain (NICD) to alter gene expression. Forty feline mammary lesions (34 malignant, 6 benign/hyperplastic) were submitted for immunohistochemical (IHC) analysis of NICD using an anti-feline NICD monoclonal antibody. Association between NICD expression in the carcinomas and both morphologic parameters and overall survival (OS) were investigated. NICD nuclear expression was observed in benign lesions (100%) while cytoplasmic localisation was evident in carcinomas (0% nuclear positive; 87.5% cytoplasmic positive; 12.5% negative). Cytoplasmic NICD localisation was statistically associated with carcinomas while nuclear staining was associated with hyperplasia. No significant correlation between positive or negative IHC NICD expression and OS or morphological parameters investigated was detected. NOTCH-1 activation, immunohistochemically identified by the NICD active form, seems to play a role in feline mammary carcinoma biology since the majority of tumours express this protein. Nuclear localisation is consistent with the traditional NICD metabolic intra-nuclear pathway while cytoplasmic accumulation suggests an aberrant NOTCH-1 signaling typical of carcinomatous transformation.

Aberrant sub-cellular immuno-localisation of NOTCH-1 activated intracellular domain (NICD) in feline mammary tumours

RESSEL, LORENZO;POLI, ALESSANDRO;
2014

Abstract

NOTCH-1 is a trans-membrane receptor protein. Ligand proteins expressed on the surface of neighbouring cells bind to the NOTCH-1 extracellular domain by juxtacrine signaling and release the NOTCH-intracellular-domain (NICD) to alter gene expression. Forty feline mammary lesions (34 malignant, 6 benign/hyperplastic) were submitted for immunohistochemical (IHC) analysis of NICD using an anti-feline NICD monoclonal antibody. Association between NICD expression in the carcinomas and both morphologic parameters and overall survival (OS) were investigated. NICD nuclear expression was observed in benign lesions (100%) while cytoplasmic localisation was evident in carcinomas (0% nuclear positive; 87.5% cytoplasmic positive; 12.5% negative). Cytoplasmic NICD localisation was statistically associated with carcinomas while nuclear staining was associated with hyperplasia. No significant correlation between positive or negative IHC NICD expression and OS or morphological parameters investigated was detected. NOTCH-1 activation, immunohistochemically identified by the NICD active form, seems to play a role in feline mammary carcinoma biology since the majority of tumours express this protein. Nuclear localisation is consistent with the traditional NICD metabolic intra-nuclear pathway while cytoplasmic accumulation suggests an aberrant NOTCH-1 signaling typical of carcinomatous transformation.
Ressel, Lorenzo; Else, R; Poli, Alessandro; Argyle, D.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/316467
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