Smad4-expression is decreased in breast cancer tissues: a retrospective study.
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.
Stuelten
Christina H
CH
Department of Clinical Chemistry, Robert Bosch Hospital, Stuttgart, Germany. chrisstu@mail.nih.gov
Buck
Miriam B
MB
Dippon
Juergen
J
Roberts
Anita B
AB
Fritz
Peter
P
Knabbe
Cornelius
C
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
D011960:Receptors, Estrogen; D018125:Receptors, Transforming Growth Factor beta; C497796:SMAD4 protein, human; D051901:Smad4 Protein