Role of extracellular signal-regulated kinase 5 (ERK5) in human breast cancer.
Authors: CM Watson, D Kipgen, C Orange, S Tovey, TG Cooke, J Edwards, HY Leung
Journal: Cancer Research (2009)

Abstract Abstract #4042 Background&amp;#x2028; ERK5 is a novel member of the mitogen-activated protein kinase (MAPK) family. MAPKs regulate multiple cellular functions, including proliferation, differentiation and survival. Recent studies have implicated the ERK5 pathway in human breast cancer. As breast cancer is now the most common type of cancer in the UK, research into this potential biomarker is essential.&amp;#x2028; Method&amp;#x2028; An optimised immunohistochemistry protocol (McCracken S. Oncogene 2008) was applied to examine expression of ERK5 in a cohort of 10 normal breast samples and 402 estrogen receptor (ER) positive breast cancer specimens from patients treated with Tamoxifen. ERK immunoreactivity was quantified using a weighted histoscore method (Kirkegaard T. Histopathology 2006), and the data was corroborated to clinico-pathologic parameters including the HER family (Tovey S. Clin Can Res. 2005).&amp;#x2028; Results&amp;#x2028; Of 402 tumours on the TMA, 346 cases were informative. Follow-up was available for a minimum of 10 years: 239 with stable disease, 94 cases recurred (13 with bilateral recurrence) and 84 received adjuvant chemotherapy.&amp;#x2028; ERK5 expression in the tumour cohort was observed in the cytoplasm with 78% of samples having weak staining with a histoscore of &amp;lt;100, 20% with moderate staining with a score between 100-200 and 2% with strong staining, histoscore&amp;gt;200. ERK5 expression in the nucleus demonstrated 85% of cores with a histoscore &amp;lt;100 (weak) and 15% between 100-200 (moderate). Almost all ERK5 membrane staining was weak (99% had a histoscore of &amp;lt;100). ERK5 cytoplasmic and nuclear expression were directly associated (c.c.=0.682, p&amp;lt;0.001) and ERK5 nuclear expression showed a trend for association with tumour size (p=0.069). In addition, ERK5 cytoplasmic expression was weakly associated with HER1-3 positivity (p=0.022) and nodal status (p=0.039). Interestingly, both cytoplasmic and nuclear ERK5 expression correlated with cytoplasmic and nuclear ERK1/2 expression (p=0.001 and p=0.003, respectively).&amp;#x2028; All of the benign breast cases expressed cytoplasmic ERK5 at a relatively weak level (100% with a histoscore&amp;lt;100). Again cytoplasmic and nuclear expression in the benign cohort correlated (c.c. =0.879 and p=0.001). Benign and tumour breast tissue expressed significantly different levels of nuclear ERK5 (p=0.002).&amp;#x2028; Discussion &amp;#x2028; This study demonstrates that ERK5 is commonly expressed in breast cancer specimens. ERK5 nuclear expression was shown to be related to tumour size, suggesting a potential role in proliferation. In support of this observation ERK5 expression also strongly correlated with expression of ERK1/2 in this cohort. ERK5 was also shown to be associated with nodal status and HER1-3 expression. Therefore our data supports the need for further investigation into the role of ERK5 in breast cancer, including ER negative patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4042.