title: Low ING4 protein expression detected by paraffin-section immunohistochemistry is associated with poor prognosis in untreated patients with gastrointestinal stromal tumors.
abstract: BACKGROUND
  Inhibitor of growth 4 (ING4) has deserved attention as a tumor suppressor gene in many malignant tumors. In our study, we investigated ING4 immunoexpression in gastrointestinal stromal tumors (GISTs) and its prognostic value.
  
  
  METHODS
  The expression of ING4 and Ki67 was investigated in 41 samples of various risk gastrointestinal stromal tumors by immunohistochemical technique. The associations of ING4 expression and clinicopathological parameters, and prognosis of the patients, were analyzed by multivariate Cox regression analysis.
  
  
  RESULTS
  ING4 expression showed a decreased trend from lower-risk to high-risk gastrointestinal stromal tumors, and an opposite trend for Ki67 expression. In lower-risk tumors, it was found the expression level of ING4 was 78.95 % ± 27.90 % and that of Ki67 was 4.42 % ± 3.75 %. However, in high-risk tumors, the expression level of ING4 was 9.23 % ± 7.66 % and that of Ki67 was 18.50 % ± 9.09 %. There was a strongly negative correlation between the expression levels of ING4 and Ki67. A significant difference was observed in the expression of ING4 between invasion and non-invasion (p < 0.001). The expression of ING4 was markedly correlated with tumor size (p < 0.001), mitotic index (p < 0.001), tumor necrosis (p = 0.021), invasion (p < 0.001), recurrence and metastasis (p = 0.021), and mortality (p < 0.001).
  
  
  CONCLUSIONS
  The low expression level of ING4 protein was correlated with high-risk GISTs. ING4 might be involved in the progression of GISTs and inhibit its invasion. ING4 might be one of the prognostic indicators in GISTs.
authors.affiliation: Department of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, 150 Haping Street, Harbin, 150040, China.
authors.forename: Abiyasi
authors.initials: A
authors.lastname: Nanding
authors.forename: Liping
authors.initials: L
authors.lastname: Tang
authors.forename: Limin
authors.initials: L
authors.lastname: Cai
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Jingshu
authors.initials: J
authors.lastname: Geng
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ning
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Li
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018398:Homeodomain Proteins / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000032:analysis* / Q000378:metabolism; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D019394:Ki-67 Antigen; D025521:Tumor Suppressor Proteins