Dissertation > Excellent graduate degree dissertation topics show

Diagnostic Significance of DOG-1and PKC-θ Expression and C-kit/PDGFRA Mutations in Gastrointestinal Stromal Tumors

Author: WangChao
Tutor: DuanXiuMei
School: Jilin University
Course: Immunology
Keywords: Gastrointestinal stromal tumors CD117 DOG-1 PKC-θ c-Kit gene PDGFRAgene
CLC: R735
Type: Master's thesis
Year: 2013
Downloads: 59
Quote: 0
Read: Download Dissertation


Background Gastrointestinal stromal tumors (GISTs) are a subtype oftumors originating from gastrointestinal mesenchymal tissues.The diagnosis ofGISTs is mainly dependent on morphological features and immunologicalstaining (i.e. KIT/CD117) in combination with detection of biomarkers ofsmooth muscle cells and nerve-derived differentiation markers (i.e. to excludegastrointestinal muscle or nerve derived tumors). Immunohistochemistry (IHC)for CD117and CD34is the most valuable method for diagnosing a GIST.However, clinical data have shown that in about4%to10%of casesimmuno-negative for CD117, the histological analysis suggests the existenceof gastrointestinal stromal tumors. It is known that other tumors can expressCD117, including melanoma, endometrial stromal tumors, adenoid cysticcarcinoma, and solitary fibrous tumor. Some of these tumors are difficult todistinguish with GISTs. Recent studies using gene expression profiling haveidentified two genes highly expressed in GISTs, DOG-1(Discovered OnGIST-1) and protein kinase C-θ (PKC-θ). DOG-1is a calcium-dependentreceptor-activated chloride ion channel protein[41]. Studies have shown thatDOG-1has a better sensitivity and specificity in the diagnosis of GISTs thanCD117[3]. About30%of the CD117negative cases are DOG-1positive. PKC-θis also overexpressed in GISTs[4]. In particular, PKC-θ has an importantdiagnostic value in CD117-negative GISTs. Only a few studies have evaluatedthe sensitivity of DOG-1and PKC-θ for the diagnosis of GISTs.Objective To investigate DOG-1and PKC-θ expression in GISTs to determine the sensitivity, specificity and diagnostic value of these twoantigens.Methods Immnunohistochemistry (IHC) was used to detect CD117,DOG-1, PKC-θ, CD34, Ki-67, α-SMA, S100and Desmin expression in147GISTs and51non-GISTs. c-Kit gene (exons9,11,13and17) and PDGFRAgene (exons12and18) mutations were also detected.Results139out of147(94.5%) GISTs were immuno-positive for CD117,141out of147(96%) were for DOG-1while133out of147(90.5%) were forPKC-θ. DOG-1had a specificity of100%, while CD117and PKC-θ had aspecificity of90%and80%, respectively. There was no significant differencebetween DOG-1and PKC-θ expressions when compared to CD117expression. CD117was detected in9.8%non-GISTs, including4cases ofadenoid cystic carcinoma and1case of melanoma. PKC-θ was expressed in4cases of leimyoma,1case of melanoma and5cases of neurilemmoma. Allcases were DOG-1negative. In30out of42(71.5%) GISTs a c-Kit genemutation was found; and in3out of42cases (7%), PDGFRA was mutated.Wild type c-Kit/PDGFRA genes accounted for21.5%(9/42). Most c-Kit genemutations were found to be located at exon11, mainly as in-frame deletions.Mutations in exon9were all missense mutations. Most PDGFRA genemutations were found in exon18, codon842. c-Kit gene mutations in exons13and17, and the PDGFRA gene mutation in exon12were not detected.Conclusions1. DOG-1expression has slightly higher thanCD117.compared to CD117, DOG-1is a biomarker with higher sensitivity andspecificity. In combination with CD117, DOG-1can be used to improve thediagnosis of GIST.2. PKC-θ can be applied as a useful biomarker, especiallyin CD117and/or DOG-1cases.3.The majority of GIST occur c-Kit genemutations, some PDGFRA mutations in GIST cases occur the case of c-kit gene mutations existence;4.c-Kit gene mutation mainly occured in exon11,followed by exon9, PDGFRA gene mutation mainly occurred in exon18;5.CD117-negative cases and PKC-θ-negative cases both had c-Kit exon11and (or)PDGFRA mutation, This indicates detection of c-Kit and PDGFRAmutations are valuable for GIST diagnosis and help determining the treatmentoptions of patients with gastrointestinal stromal tumors.

Related Dissertations

  1. Effects of Chinese Medicine Herbs Jiegusan on Fracture Healing in Dogs,S858.292
  2. The Establishment and Application of cPL Double Anti-Body Sandwich Elisa Method for the Diagnosis of Canine Acute Pancreatisis,S858.292
  3. Study on the Anesthestic Quality, Blood Concentration and Clinical Application of Shumianning Administered Intravenously by Continuous Rate Infusion Using Microinjection Pump in Dogs,R965
  4. Expression and Significance of HIF-1α on the Insulin Resistance during the Injury of Reperfusion of Ischemic Myocardium in Dog Undergoing Cardiopulmonary Bypass,R654.1
  5. Clinical Analysis of Postoperative Recurrent-metastatic Gastrointestinal Stromal Tumors,R735
  6. The Correlation Between Clinicopathologic Features and Risk Classification of Gastrointestinal Stromal Tumors,R735
  7. Expression and Significance of DOG1 in CD117 Negative Gastrointestinal Stromal Tumor,R735
  8. CT Perfusion to Monitor the Liver Fibrosis-liver Cirrhosis of Chinese Countryside Dogs Preliminary Study,R575.2
  9. Study on the Relationship between Piral CT Features and the Expression of MMP-9 and Hpa in Gastrointestinal Stromal Tumor,R735
  10. Establishment of an Implanted Model of Human Gastrointestinal Stromal Tumors in Nude Mice and Observation Their Biological Characters,R735
  11. The Experimental Study on Blood Purification Therapy Canine Model of Tetrachloride-induced Acute Liver Failure,R575.3
  12. Split within the domestic canine thoracic aorta stent implantation experimental study,R-332
  13. The Celecoxib improve k562 cell sensitivity to IFN -α,R733.7
  14. Gastrointestinal stromal tumors , treatment and new progress,R735
  15. The Expression and Significance of Medullary System Antigens in Multiple Myeloma,R733.3
  16. Constructing the Canine Model of Brugada Syndrome and Electrophysiological Effects of Cilostazol,R541.7
  17. 144 cases of gastrointestinal stromal tumor treatment and prognosis,R735
  18. Uterine malignant mixed mesodermal tumor clinicopathologic features and CD10, CD117 gene expression,R737.33
  19. New temporary metal stents canine cardiac achalasia experimental study,R571
  20. The Correlations Between Connexin Protein and Myocardial Fibrosis in Rapid Atrial Pacing Canine Model of Atrial Fibrillation,R541.75
  21. Expression and Significance of CD117 and CD133 in DEN-Induced Rats Hepatocarcinoma,R735.7

CLC: > Medicine, health > Oncology > Gastrointestinal Cancer
© 2012 www.DissertationTopic.Net  Mobile