title: Constitutive activation of signal transducers and activators of transcription 3 correlates with better prognosis, cell proliferation and hypoxia-inducible factor-1α in human gastric cancer.
abstract: OBJECTIVE
  We aimed to investigate the biological significance of signal transducers and activators of transcription 3 (STAT3) in gastric carcinoma.
  
  
  METHODS
  Immunohistochemistry was performed on tissue array slides containing 285 gastric carcinoma specimens. The relationship between the nuclear expression of phospho-Tyr705-STAT3 (pSTAT3), an active form of STAT3, and prognosis, clinicopathological factors, proliferation, cell cycle regulators, apoptosis regulators, or angiogenesis-related proteins was evaluated.
  
  
  RESULTS
  In nonneoplastic gastric mucosa, pSTAT3 was observed primarily in the nuclei of cells in the proliferative zone and intestinal metaplasia. In gastric carcinomas, nuclear STAT3 activation was observed in 36% of cases and was positively correlated with the Ki-67 labeling index and earlier tumor stage, whereas it was inversely correlated with lymphatic metastasis and distant metastasis (p< 0.05). Moreover, survival analyses showed that pSTAT3 expression was an independent prognostic factor of good survival. In addition, the expression of nuclear pSTAT3 positively correlated with that of cyclin D1, p21, p27, hypoxia-inducible factor-1α, or vascular endothelial growth factor (p< 0.05).
  
  
  CONCLUSIONS
  STAT3 activation is an early event in gastric tumorigenesis and significantly correlates with better prognosis, proliferation and angiogenesis. Thus, STAT3 activation may be a valuable prognostic variable and therapeutic target in gastric carcinoma.
authors: Department of Anatomy, Medical Research Center, Seoul National University College of Medicine, Korea.
authors: Sungmin
authors: S
authors: Woo
authors: Byung Lan
authors: BL
authors: Lee
authors: Jiyeon
authors: J
authors: Yoon
authors: Sung Jin
authors: SJ
authors: Cho
authors: Tai-Kyoung
authors: TK
authors: Baik
authors: Mee Soo
authors: MS
authors: Chang
authors: Hee Eun
authors: HE
authors: Lee
authors: Jong-Wan
authors: JW
authors: Park
authors: Young-Hoon
authors: YH
authors: Kim
authors: Woo Ho
authors: WH
authors: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D042501:Angiogenic Proteins / Q000032:analysis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D018797:Cell Cycle Proteins / Q000032:analysis; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D005260:Female; D005743:Gastrectomy; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D016016:Proportional Hazards Models; D056910:Republic of Korea; D050796:STAT3 Transcription Factor / Q000032:analysis*; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D014443:Tyrosine
chemical_list: D042501:Angiogenic Proteins; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014443:Tyrosine