title: Prognostic angiogenic markers (endoglin, VEGF, CD31) and tumor cell proliferation (Ki67) for gastrointestinal stromal tumors.
abstract: OBJECTIVE
  To evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor (VEGF)], proliferative index (Ki67), and prognosis of patients with gastrointestinal stromal tumors (GIST).
  
  
  METHODS
  This is a retrospective study of 54 GIST cases. Medical records were searched to obtain the GIST patients' demographic and clinical data, and paraffin-embedded blocks of tumor samples were retrieved from the hospital archives to conduct a new immunohistochemical evaluation. The tumor samples of GIST patients were subject to immunohistochemical evaluation for endoglin (CD105), CD31, VEGF, and Ki67 expression. The CD105 and CD31 intratumoral microvascular density (IMVD) was measured using automated analysis. We determined the correlation between the immunoexpression of CD105, CD31, VEGF, Ki67 and prognosis. In addition, we conducted a cutoff analysis using the receiver-operating characteristic curve. VEGF positivity was classified as either null/weak or strong. Ki67 was evaluated using a cutoff of 5% positive cells. The prognosis was classified as good (patient alive without recurrence) or poor (patient with recurrence/death).
  
  
  RESULTS
  The distribution of tumor sites among the 54 analyzed samples was as follows: 27 (50%) in the stomach, 20 (37.1%) in the small intestine, 6 (11.1%) in the colon, and 1 (1.8%) in the esophagus. The size of the tumors ranged from 2 to 33 cm (median: 8 cm); in 12 cases (22.2%), the tumor was below 5 cm at the largest diameter, but in 42 cases (77.7%), the tumor was larger than 5 cm. The means of CD105 and CD31 were significantly higher in the group with poor prognosis (P < 0.001). The cut-off values of CD105 (> 1.2%) and CD31 (> 2.5%) in the receiver-operating characteristic curve were related to a poorer prognosis. Cases with a better prognosis showed significantly null/weak staining for VEGF (P < 0.001). Ki-67 expression of ≥ 5% was strongly correlated with a worse prognosis (P < 0.001). In the multivariate analysis, CD105 was the variable that most strongly correlated with prognosis.
  
  
  CONCLUSIONS
  The IMVD cutoff values for the angiogenic markers CD105 and CD31, may be prognostic factors for GIST, in addition to VEGF and Ki67.
authors.affiliation: Rodrigo Panno Basilio-de-Oliveira, Pathology Post-Graduate Program, Federal University of Rio de Janeiro, Rio de Janeiro 21941-901, Brazil.
authors.forename: Rodrigo Panno
authors.initials: RP
authors.lastname: Basilio-de-Oliveira
authors.affiliation: Rodrigo Panno Basilio-de-Oliveira, Pathology Post-Graduate Program, Federal University of Rio de Janeiro, Rio de Janeiro 21941-901, Brazil.
authors.forename: Vera Lucia Nunes
authors.initials: VL
authors.lastname: Pannain
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis*; D019540:Area Under Curve; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D000071063:Endoglin; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D046152:Gastrointestinal Stromal Tumors / Q000098:blood supply / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis*; D011237:Predictive Value of Tests; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; CD31; Gastrointestinal stromal tumors; Immunohistochemistry, CD105; Ki-67; Vascular endothelial growth factor