title: High nuclear phosphorylated extracellular signal-regulated kinase expression associated with poor differentiation, larger tumor size, and an advanced stage of breast cancer.
abstract: Extracellular signal-regulated kinase (ERK1/2) is implicated in the malignant behavior of breast cancer cells. However, previous clinical-pathological studies have shown that expression of activated/phosphorylated ERK1/2 is not associated with enhanced proliferation and invasion of mammary carcinomas. ERK1/2 is expressed in the cytoplasm, and activated/phosphorylated ERK1/2 translocates to the nucleus. The aim of this study is to evaluate nuclear phosphorylated ERK1/2 as a biomarker for breast cancer prognosis. The clinical-pathological relation of cytoplasmic/nuclear phosphorylated ERK1/2 was analyzed in 105 surgically resected breast cancer specimens by immunohistochemistry with tissue microarray. The results showed that non-neoplastic breast tissue mainly showed faint phosphorylated ERK1/2 staining. No statistically significant association was found between the level of cytoplasmic phosphorylated ERK1/2 expression and the clinical features of the disease. High nuclear phosphorylated ERK1/2 expression was associated with high grade (poor differentiation, p = = 0.010), high T status (larger tumor size, p = 0.033), and an advanced stage (p = 0.018) of the disease. Thus, nuclear phosphorylated ERK1/2 is associated with enhanced proliferation and invasion of mammary carcinomas and may be a biomarker for breast cancer prognosis and the determination of therapeutic strategies.
authors.affiliation: Cheng-Jeng Tai, MD, Department of Internal Medicine, Taipei Medical University Hospital, No. 250,Wu-Hsing St., Taipei 11031, Taiwan, tel. 886-2-27372181, fax 886-2-2736-3051., e-mail: cjtai@tmu.edu.tw.
authors.forename: Hsing-Tao
authors.initials: HT
authors.lastname: Kuo
authors.forename: Hui-Tao
authors.initials: HT
authors.lastname: Hsu
authors.forename: Chun-Chao
authors.initials: CC
authors.lastname: Chang
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Jiang
authors.forename: Chung-Min
authors.initials: CM
authors.lastname: Yeh
authors.forename: Ko-Hung
authors.initials: KH
authors.lastname: Shen
authors.forename: Pei-Chi
authors.initials: PC
authors.lastname: Hsu
authors.forename: Cheng-Jeng
authors.initials: CJ
authors.lastname: Tai
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3