title: Diagnostic significance of DOG-1 and PKC-θ expression and c-Kit/PDGFRA mutations in gastrointestinal stromal tumours.
abstract: OBJECTIVE
  To investigate discovered on gastrointestinal stromal tumor (GIST)-1 (DOG-1) and protein kinase C-θ (PKC-θ) expression in a series of GISTs and determine the sensitivity, specificity, and diagnostic value of these two antigens.
  
  
  METHODS
  Immnunohistochemistry (IHC) was used to detect CD117, DOG-1, PKC-θ, CD34, Ki-67, α-smooth muscle actin (SMA), S100, and Desmin expression in 147 GISTs and 51 non-GISTs. c-Kit gene (exons 9, 11, 13, and 17) and platelet-derived growth factor receptor-alpha (PDGFRA) gene (exons 12 and 18) mutations were also detected.
  
  
  RESULTS
  About 94.5% GISTs were CD117 positive, 96% were DOG-1 positive, and 90.5% were PKC-θ positive. DOG-1 had a specificity of 100%, while CD117 and PKC-θ had a specificity of 90% and 80%, respectively. There was no significant difference between DOG-1 and PKC-θ expressions when compared to CD117 expression. In 30 out of 42 (71.5%) GISTs, a c-Kit gene mutation was found, and in 3 out of 42 cases (7%), PDGFRA was mutated. Wild-type c-Kit/PDGFRA genes accounted for 21.5% (9/42). Most c-Kit gene mutations were found to be located at exon 11, mainly as in-frame deletions. Mutations in exon 9 were all missense mutations. Most PDGFRA gene mutations were found in exon 18, codon 842. c-Kit gene mutations in exons 13 and 17, and the PDGFRA gene mutation in exon 12 were not detected.
  
  
  CONCLUSIONS
  Compared to CD117, DOG-1 is a biomarker with higher sensitivity and specificity. The combination of CD117 and DOG-1 can be used to improve the diagnosis of GIST. Although PKC-θ has a lower specificity than DOG-1, it can be a useful biomarker, especially in CD117(-) and/or DOG-1(-) cases.
authors.affiliation: Pathological Diagnosis Center, First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Mei-Shan
authors.initials: MS
authors.lastname: Jin
authors.forename: Ya-Bin
authors.initials: YB
authors.lastname: Zou
authors.forename: Jing-Na
authors.initials: JN
authors.lastname: Gao
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Peng
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Wang
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Wu
authors.forename: Yin-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Duan
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D000075369:Anoctamin-1; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D018118:Chloride Channels / Q000032:analysis*; D003893:Desmin / Q000032:analysis; D005091:Exons; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics*; D046152:Gastrointestinal Stromal Tumors / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis*; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000032:analysis*; D011493:Protein Kinase C / Q000032:analysis*; D000074121:Protein Kinase C-theta; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D009418:S100 Proteins / Q000032:analysis; D012680:Sensitivity and Specificity
chemical_list: C541116:ACTA2 protein, human; C476213:ANO1 protein, human; D000199:Actins; D000075369:Anoctamin-1; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D018118:Chloride Channels; D003893:Desmin; D007527:Isoenzymes; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009418:S100 Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta