The ubiquitin-binding protein p62 is expressed in breast cancers showing features of aggressive disease.
p62 is a multi-functional protein, which induces nuclear factor-kappaB (NFkappaB) activation through multiple upstream signalling pathways, including those triggered by the epidermal growth factor (EGF) family of receptors. We hypothesised that p62 overexpression increased EGF family receptor expression and worse outcome in breast cancer would be associated. We stained a tissue microarray representing 523 breast cancers using a commercial guinea pig anti-human p62 sera and standard immunohistochemical methods to address this. Out of n = 106 tumours, 20.3% stained positively. p62 expression correlated with grade (P = 0.010) and distant metastasis (P = 0.04) and EGF receptor (EGFR) (P = 0.012), HER2 (P = 0.016), HER3 (P = 0.007) and HER4 (0.002) expressions. Though expression correlated with reduced 5-year survival (58.5 vs 73.6%), there was no association with overall disease specific survival. p62 expression may represent a marker of activation of the NFkappaB pathway.
Rolland
Phil
P
Academic and Clinical Department of Oncology, Institute of Infections and Immunity, University of Nottingham, Nottingham City Hospital NHS Trust, Nottingham NG5 1PB, UK.
Madjd
Zahra
Z
Durrant
Lindy
L
Ellis
Ian O
IO
Layfield
Rob
R
Spendlove
Ian
I
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism; D066247:Receptor, ErbB-4; D000071456:Sequestosome-1 Protein; D046888:Tissue Array Analysis
D048868:Adaptor Proteins, Signal Transducing; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D000071456:Sequestosome-1 Protein; C099718:SQSTM1 protein, human; C587689:ERBB4 protein, human