Expression of DOG1, CD117 & PDGFRA in Gastrointestinal Stromal Tumours and Correlations with Clinicopathological Features & Risk Assessment

Abstract

BACKGROUND Gastrointestinal stromal tumour (GIST) was first named in 1983. Gastrointestinal stromal tumours (GISTs) are a special kind of tumours which are derived from mesenchymal tissues of gastrointestinal tract and arises from the interstitial cells of Cajal, the pacemaker cells of the gastrointestinal (GI) tract responsible for the contractions of smooth muscles.1 Determination of the type of mutations in GIST plays a major role in assessing the risk of progression of the disease and also allows determination of the clinical management and treatment. More accurate GIST diagnosis is possible by using simultaneously various types of antibodies to immunohistochemistry methods in routine procedures.2 METHODS In this descriptive cross sectional study expression of DOG1, CD117 & PDGFRA was analysed in 70 patients with histopathologically diagnosed specimens of gastrointestinal stromal tumour, received in the Department of Pathology, Government Medical College, Thiruvananthapuram, using the immunohistochemical method. RESULTS On evaluating the CD117, DOG1 & PDGFRA expression in GIST by immunohistochemistry showed 71.4%, 84.3% and 55.7% positivity respectively. Most of the patients fall in the age group of 60 – 70 years with a slight male predominance. Most common location of GIST is stomach with tumour size of 5 – 10cm. On microscopic evaluation spindle type GIST was predominant histopathological type. Considering the risk groups, histological type, mitotic count and tumour size, PDGFRA expression is more in low-risk groups. PDGFRA expression has insignificant relation with clinicopathologic features including age, sex, site of lesion, risk groups, histologic type, mitotic count and tumour size. Relationship between positive expression by CD117 & DOG1 with risk group & site of lesion are not statistically significant. When compared to the similar studies in literature, the obtained results are concordant. CONCLUSIONS Our study concluded that, 71.4% positive immunoreactions for CD117, 84.3% positive immunoreactions for DOG1 & 55.7% positive immunoreactions for PDGFRA. PDGFRA expression has insignificant relation with clinicopathologic features including age, sex, site of lesion, risk groups, histologic type, mitotic count and tumour size. Relationship between positive expression by CD117 & DOG1 with risk group & site of lesion are not statistically significant. The importance of this study is that PDGFRA expression in tumours can be considered for treatment by using tyrosine kinase inhibitors and avapritinib. So PDGFRA testing in GIST show a new path in the targeted therapy. KEY WORDS GIST (Gastrointestinal Stromal Tumour), Discovered on GIST 1(DOG1), Cluster of Differentiation (CD117), Platelet Derived Growth Factor Receptor A(PDGFRA), Anoctamin 1(ANO1), Succinate Dehydrogenase (SDH), Risk Group, Mitotic Count