title: Smad4-expression is decreased in breast cancer tissues: a retrospective study.
abstract: BACKGROUND
  Although transforming growth factor beta (TGF-beta) typically inhibits proliferation of epithelial cells, consistent with a tumor suppressor activity, it paradoxically also exhibits pro-metastatic activity in the later stages of carcinogenesis. Since tumors often display altered TGF-beta signaling, particularly involving the Smad-pathway, we investigated the role of Smad4-expression in breast cancer.
  
  
  METHODS
  Smad4 expression was investigated by immunohistochemistry in formalin-fixed, paraffin-embedded tissue from 197 samples of primary breast cancer obtained between 1986 and 1998. The prognostic value of Smad4-expression was analyzed.
  
  
  RESULTS
  Smad4 expression was found to be reduced in lobular and ductal breast carcinoma as compared to surrounding uninvolved lobular and ductal breast epithelia (p < 0.001, n = 50). Smad4-expression correlated positively with expression of TGF-beta-receptor I (p < 0.001, n = 197) and TGF-beta-receptor II (p < 0.001, n = 197), but showed no significant correlation with tumor size, metastases, nodal status, histological grade, histological type, or estrogen receptor expression. While not achieving statistical significance, there was a trend towards longer survival times in patients with Smad4 negative tumors.
  
  
  CONCLUSIONS
  According to the suggested role of Smad4 as a tumor suppressor we observed that expression of Smad4 is lower in human breast cancer than in surrounding breast epithelium. However, we also observed a trend towards longer survival times in Smad4-negative patients, indicating the complex role of TGF-beta signaling in tumor progression.
authors.affiliation: Department of Clinical Chemistry, Robert Bosch Hospital, Stuttgart, Germany. chrisstu@mail.nih.gov
authors.forename: Christina H
authors.initials: CH
authors.lastname: Stuelten
authors.forename: Miriam B
authors.initials: MB
authors.lastname: Buck
authors.forename: Juergen
authors.initials: J
authors.lastname: Dippon
authors.forename: Anita B
authors.initials: AB
authors.lastname: Roberts
authors.forename: Peter
authors.initials: P
authors.lastname: Fritz
authors.forename: Cornelius
authors.initials: C
authors.lastname: Knabbe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D012189:Retrospective Studies; D051901:Smad4 Protein / Q000032:analysis*; D015996:Survival Rate
chemical_list: D011960:Receptors, Estrogen; D018125:Receptors, Transforming Growth Factor beta; C497796:SMAD4 protein, human; D051901:Smad4 Protein