Effect of different ERK2 protein localizations on prognosis of patients with invasive breast carcinoma.
Mitogen-activated protein kinase (MAP kinase) pathways represent a cascade of phosphorylation events, including three pivotal kinases, Raf, MEK and ERK1/2, which have been implicated in the pathogenesis of cancer. We examined 151 cases of invasive breast carcinoma by immunohistochemistry and compared the ERK2 expression with clinicopathological parameters, MMP-11 immunoexpression and patients' survival. ERK2 immunoexpression was detected in the cytoplasm and nucleus of cancer cells in 37.7% and 19.2% of cases, respectively. Nuclear ERK2 was inversely correlated with ER (p = 0.039), whereas cytoplasmic ERK2 was positively correlated with MMP-11 in fibroblasts (p = 0.032) and more often expressed in lobular than ductal carcinomas (p = 0.026). Nuclear ERK2 expression was found to be an independent prognostic factor of shortened overall survival of patients (p = 0.040), while cytoplasmic ERK2 had an independent, favorable effect on both disease-free and overall survival (p < 0.0001 and p = 0.002, respectively). These findings suggest that the different subcellular localizations of ERK2 seem to be related to different, possibly contradictory, effects on patient survival.
Nakopoulou
L
L
School of Medicine, National and Kapodistrian University of Athens, Greece. lnakopou@cc.uoa.gr
Mylona
E
E
Rafailidis
P
P
Alexandrou
P
P
Giannopoulou
I
I
Keramopoulos
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000378:metabolism; D018275:Carcinoma, Lobular / Q000175:diagnosis / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases / Q000378:metabolism; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D011379:Prognosis
D015415:Biomarkers; D019950:Mitogen-Activated Protein Kinase 1; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases