Prognostic significance of the expression of Smad4 and Smad7 in human gastric carcinomas.
BACKGROUND
Transforming growth factor-beta (TGF-beta) modulates the growth and function of many cells, including those with malignant transformation. Smad proteins have been identified as major components in the intracellular signaling of TGF-beta family members.


METHODS
To clarify the correlations between clinicopathologic profiles and the patient's survival, the expression of common mediator Smad (Smad4) and inhibitory Smad (Smad7) were evaluated immunohistochemically in 304 consecutive gastric carcinomas using the tissue array method.


RESULTS
Positive Smad4 expression was observed in 266 (87.5%) tumors and positive Smad7 expression in 98 (32.2%) tumors. The prognosis of patients with a Smad4-positive tumor was significantly better than that of the patients with a negative tumor. The survival rate was significantly higher in patients with negative Smad7 expression than those with positive Smad7 expression. In subgroup analysis according to TNM (tumour-node-metastasis) stage, both Smad4 and Smad7 showed most significant prognostic differences in stage I gastric cancer patients. Multivariate analysis indicated that tumor size, depth of invasion, lymph node metastasis and Smad7 expression were independent prognostic factors.


CONCLUSIONS
Enhanced expression of the TGF-beta signaling inhibitor Smad7 may present one of the novel mechanisms of TGF-beta resistance in human gastric carcinomas.
Kim
Y H
YH
Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Lee
H S
HS
Lee
H-J
HJ
Hur
K
K
Kim
W H
WH
Bang
Y-J
YJ
Kim
S-J
SJ
Lee
K U
KU
Choe
K J
KJ
Yang
H-K
HK
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D051901:Smad4 Protein; D051906:Smad7 Protein; D013274:Stomach Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis; D015996:Survival Rate; D015534:Trans-Activators / Q000032:analysis*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; C497806:SMAD7 protein, human; D051901:Smad4 Protein; D051906:Smad7 Protein; D015534:Trans-Activators