title: Prognostic significance of PTEN, Ki-67 and CD44s expression patterns in gastrointestinal stromal tumors.
abstract: OBJECTIVE
  To develop a prognostic approach for gastrointestinal stromal tumors (GISTs) using a cluster of indicators and follow-up information.
  
  
  METHODS
  One hundred and four GISTs that had not been subjected to targeted therapies were collected and classified by NIH risk assessment and anatomic location. By immunohistochemistry, the expressions of PTEN, Ki-67, CD44s matrix metalloproteinase (MMP)-9 and TIMP-1 were detected on tissue microarray. Univariate and multimarker survival analyses were performed and then a COX hazard proportion model was constructed to evaluate a cluster of predictors of GIST.
  
  
  RESULTS
  Our data showed small intestinal GIST are more aggressive than gastric GIST. The NIH risk assessment correlated with disease-free survival for either gastric GIST or small intestinal GIST. Immunohistochemical analysis revealed that Ki-67 labeling indexes (LIs) < 5% predicted higher disease-specific survival (DSS) in gastric and small intestinal GIST. CD44s positivity and PTEN LIs ≥ 50% correlated with higher DSS in gastric GIST. MMP-9 and TIMP-1 had no correlation with survival. Multimarker analysis revealed that the expression pattern of PTEN LIs ≥ 50% combined with Ki-67 LIs < 5% and CD44s positivity reliably predicted favorable outcomes for gastric GIST (P = 0.009), as did the combination of PTEN LIs ≥ 50% and Ki-67 LIs < 5% for small intestinal GIST (P = 0.011). Authors also found that high NIH risk grade was correlated with DSS in patients with gastric GIST and disease-free survival in patients with small intestinal GIST.
  
  
  CONCLUSIONS
  PTEN LIs ≥ 50%, Ki-67 LIs < 5% and CD44s positivity provides an accurate, favorable prognosis for gastric GIST. PTEN LIs ≥ 50% and Ki-67 LIs < 5% does the same for small intestinal GIST. Ki-67 LIs enhances the NIH assessment.
authors.affiliation: Department of Pathology, Chinese PLA the 309th Hospital, Beijing 100091, China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Liang
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Li
authors.forename: Wen-Mei
authors.initials: WM
authors.lastname: Li
authors.forename: You-Yong
authors.initials: YY
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000175:diagnosis / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011379:Prognosis; D018570:Risk Assessment; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C473647:CD44S antigen; D018960:Hyaluronan Receptors; D019394:Ki-67 Antigen; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020780:Matrix Metalloproteinase 9