title: Smad3 and Smad3 phosphoisoforms are prognostic markers of gastric carcinoma.
abstract: BACKGROUND
  The transforming growth factor-β/Smads signaling pathway plays an important role in tumorigenesis and progression in cancer, and may closely be related to the biological behaviors of some malignant tumors, such as gastric carcinoma. In this study, we investigated the roles of Smad3 and Smad3 phosphoisoforms in the prognosis of gastric carcinoma.
  
  
  METHODS
  We investigated the expressions of Smad3, pSmad3C(S423/425), pSmad3L(T179), pSmad3L(S204), and pSmad3L(S213) in tumor tissue microarrays of 442 gastric carcinoma patients who underwent curative surgery using immunohistochemistry and assessed their correlation with clinical outcome.
  
  
  RESULTS
  Positive Smad3 expression was observed in 33.5 % of gastric carcinoma. The rates of positive Smad3 phosphoisoforms expression varied according to the location of phosphorylation within Smad3: pSmad3C(S423/425) 28.5 %, pSmad3L(T179) 5.9 %, pSmad3L(S204) 1.8 %, and pSmad3L(S213) 20.8 %. Positive Smad3 expression was associated with diffuse type (p = 0.003), poorer histologic differentiation (p = 0.005), more frequent lymph node metastasis (p = 0.001), and higher AJCC stage (p = 0.006). Multivariate analyses revealed that Smad3 expression (p = 0.041), pSmad3L(T179) expression (p = 0.011), pSmad3L(S213) expression (p = 0.003), and American Joint Committee on Cancer (AJCC) stage were independent predictors of shorter disease-free survival. Smad3 expression (p = 0.033), pSmad3L(T179) expression (p = 0.012), pSmad3L(S213) expression (p = 0.005), and AJCC stage were also independent predictors of shorter overall survival. pSmad3C(S423/425) expression tended to show favorable influences on both disease-free survival (p = 0.134) and overall survival (p = 0.232).
  
  
  CONCLUSIONS
  Smad3, pSmad3L(T179), and pSmad3L(S213) expression might be independent predictors of both shorter disease-free survival and shorter overall survival in gastric carcinoma patients after curative surgery, and might help clinicians identify patients at high risk of recurrence.
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea. parmedines.kim@samsung.com
authors.forename: Seok-Hyung
authors.initials: SH
authors.lastname: Kim
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Soomin
authors.initials: S
authors.lastname: Ahn
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Hyeon
authors.forename: Cheol-Keun
authors.initials: CK
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020033:Protein Isoforms / Q000378:metabolism; D056910:Republic of Korea / Q000453:epidemiology; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D020033:Protein Isoforms; C497790:SMAD3 protein, human; D051900:Smad3 Protein