@article{3115988,
    title = "Effect of the different phosphorylated Smad2 protein localizations on
the invasive breast carcinoma phenotype",
    author = "Liapis, George and Mylona, Eleni and Alexandrou, Paraskevi and and Giannopoulou, Ioanna and Nikolaou, Irini and Markaki, Sofia and and Keramopoulos, Antonios and Nakopoulou, Lydia",
    journal = "APMIS: Acta Pathologica, Microbiologica et Immunologica Scandinavica",
    year = "2007",
    volume = "115",
    number = "2",
    pages = "104-114",
    publisher = "Wiley",
    issn = "0903-4641, 1600-0463",
    doi = "10.1111/j.1600-0463.2007.apm_517.x",
    keywords = "Smad2; TGF beta; immunohistochemistry; breast cancer; invasion",
    abstract = "Smad2 participates in the TGF-beta signaling pathway, where it
cooperates with transcription factors to regulate expression of defined
genes. The purpose of this study was to investigate the expression
pattern of phosphorylated Smad2 (pSmad2) in association with
clinicopathological parameters and biological markers of proliferation
and invasion. Immunohistochemistry was applied on paraffin-embedded
sections from 164 patients with invasive breast carcinomas to detect the
expression of the proteins pSmad2, ER, PR, Ki67, topoisomerase IIa,
ERK2, catenin-p120, MMP-14 and TIMP-2. pSmad2 protein was detected in
the nuclei of the malignant cells (68.1%) and in the tumor fibroblasts
(55.2%). Nuclear pSmad2 was inversely correlated with histological
grade and LN (p=0.047 and p=0.05) as well as with Ki67 and topoIIa
(p=0.003 and p=0.021, respectively). There was also an inverse relation
between nuclear pSmad2 and normal immunoexpression of the adhesion
molecule catenin-p120 (p=0.028). Both nuclear and stromal pSmad2 were
positively correlated with ERK2 of tumor fibroblasts (p=0.008 and
p=0.0001, respectively), while stromal pSmad2 was furthermore related to
stromal MMP-14 and tumor TIMP-2 (p=0.006 and p=0.022, respectively).
Patients with high expression of cancerous pSmad2 tended to have a
better prognosis, although statistic significance was never reached.
pSmad2 was found to play a dual role, according to its distribution.
Nuclear localization was thus found to be related to a less aggressive
tumor phenotype, whereas stromal location was associated with an
invasive phenotype."
}