Lack of activated Smad2 in transforming growth factor-beta signaling is an unfavorable prognostic factor in patients with esophageal squamous cell carcinoma.
OBJECTIVE
Transforming growth factor-beta (TGF-beta) regulates cell growth in various cells, and inactivation of the TGF-beta-signaling pathway contributes to tumor progression. In this study, we investigated the expression of Smad2 and Smad3, which are specific intracellular mediators of TGF-beta signaling. We also examined the relationship between the expression levels of activated Smad2 by TGF-beta and clinicopathologic characteristics of patients with esophageal squamous cell carcinoma (SCC).


METHODS
Immunohistochemical staining with anti-phosphorylated Smad2 (P-Smad2) polyclonal antibody, anti-Smad2 monoclonal antibody, and anti-Smad3 polyclonal antibody was performed on surgical specimens obtained from 80 patients with esophageal SCC.


RESULTS
Our data indicated that a low level of P-Smad2, as detected immunohistologically, correlated with lymph node metastasis (P = 0.0002), distant metastasis (P = 0.0338), pathologic stage (P = 0.0093), and poor survival rate (P = 0.0246). All patients without positive Smad2 immunostaining were included among those without positive P-Smad2 immunostaining. There was no significant correlation between expression of Smad2 or Smad3 and clinicopathologic characteristics.


CONCLUSIONS
We demonstrated that a lack of Smad2-P appears to be correlated with tumor development and poor prognosis in patients with esophageal SCC.
Fukuchi
Minoru
M
Department of Surgery I, Gunma University Faculty of Medicine, Maebashi, Gunma, Japan. mfukuchi@med.gunma-u.ac.jp
Nakajima
Masanobu
M
Miyazaki
Tatsuya
T
Masuda
Norihiro
N
Osawa
Hidenobu
H
Manda
Ryokuhei
R
Tsukada
Katsuhiko
K
Kato
Hiroyuki
H
Kuwano
Hiroyuki
H
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000502:physiology*
D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta