title: Expression of cell polarity protein scribble differently affects prognosis in primary tumor and lymph node metastasis of breast cancer patients.
abstract: BACKGROUND
  We evaluated the relationship between the immunohistochemically determined expression of the cell polarity protein scribble to prognosis in different environments of estrogen receptor (ER) expression and epithelial-to-mesenchymal transition (EMT).
  
  
  METHODS
  We immunohistochemically evaluated the expression level of scribble in primary tumors and lymph node metastases of 225 node-positive breast cancer patients who had received chemotherapy. We then evaluated metastasis-free survival (MFS) in the absence or presence of ER and the EMT-related protein vimentin.
  
  
  RESULTS
  Among patients with ER-positive tumors, patients with low scribble expression in the primary tumor had a significantly shorter MFS than patients with high scribble expression (p = 0.0225). Furthermore, among patients with vimentin-negative tumors, patients with low expression of scribble in the primary tumor had significantly shorter MFS than patients with high expression of scribble (p = 0.0463). In contrast, among patients with vimentin-positive tumors, patients with high expression of scribble in the primary tumor had significantly shorter MFS than patients with low expression of scribble (p = 0.0343). Moreover, among patients with ER-negative tumors, patients with high expression of scribble in lymph node metastases showed significantly higher expression of E-cadherin in metastases (p = 0.0407) and had significantly shorter MFS than patients with low expression of scribble (p = 0.0064).
  
  
  CONCLUSIONS
  The prognostic significance of cell polarity depended on the ER expression and EMT. Furthermore, the preservation of cell polarity in metastases was associated with mesenchymal-to-epithelial transition and worse prognosis. Cell polarity promotes the diversity of metastasis in combination with malignancy grade in breast cancer patients.
authors: Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuoku, Chiba, 260-8677, Japan.
authors: Junta
authors: J
authors: Sakakibara
authors: Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuoku, Chiba, 260-8677, Japan. sakaki@faculty.chiba-u.jp.
authors: Masahiro
authors: M
authors: Sakakibara
authors: Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuoku, Chiba, 260-8677, Japan.
authors: Nobumitsu
authors: N
authors: Shiina
authors: Department of Breast Surgery, Chiba Rosai Hospital, 2-16, Tatsumidaihigashi, Ichihara, 290-0003, Japan.
authors: Toshihiko
authors: T
authors: Fujimori
authors: Department of Breast Surgery, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai, Fuchu, 183-8524, Japan.
authors: Yoshiyuki
authors: Y
authors: Okubo
authors: Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuoku, Chiba, 260-8677, Japan.
authors: Kaoru
authors: K
authors: Fujisaki
authors: Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuoku, Chiba, 260-8677, Japan.
authors: Takeshi
authors: T
authors: Nagashima
authors: Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuoku, Chiba, 260-8677, Japan.
authors: Takafumi
authors: T
authors: Sangai
authors: Diagnostic Pathology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuoku, Chiba, Japan.
authors: Yukio
authors: Y
authors: Nakatani
authors: Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuoku, Chiba, 260-8677, Japan.
authors: Masaru
authors: M
authors: Miyazaki
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D011960:Receptors, Estrogen; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins
keywords: Cell polarity; EMT; MET; Metastasis; Prognosis