Scripties UMCG - Rijksuniversiteit Groningen
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The Value of PDGFRA Immunohistochemistry (positive PDGFRA expression with dot-like pattern) and Histomorphology (epithelioid phenotype) for the Detection of PDGFRA Mutations in Gastrointestinal Stromal Tumors (GISTs)

(2017) Al Tahaa, H.A.S.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms that arise in the GI tract. GISTs are characterized by the presence of gain of function mutations that affect both KIT and PDGFRA genes. Determining the mutational status in these tumors is essential for their effective treatment. Genotyping is very reliable in determining the type of mutation in GISTs. However, Immunohistochemistry (IHC) with GIST histomorphology are believed to be of great value in identifying PDGFRA mutants in GIST.
Methods and Results.
PDGFRA IHC was performed on a retrospective cohort of 60 GISTs with known genotype status using the CC1 standard antigen retrieval protocol (Tris HCl buffer pH9 for 1h at 95 °C), with a rabbit monoclonal antibody (D13C6 Cell Signalling). The sample included 44 GISTs with KIT mutations, 11 GISTs with PDGFRA mutations and 5 wild type GISTs. Strong PDGFRA expression was observed in all PDGFRA mutants, in nearly half of KIT mutants and in one wild type GIST. Thus, the sensitivity and specificity of PDGFRA IHC in identifying PDGFRA mutant GISTs was 100% and 45.45% respectively in this study. However, only 5 PDGFRA-mutated GISTs of the 60 GISTs sample displayed the combination of positive PDGFRA expression with dot-like immunostaining pattern and epithelioid cell morphology. This illustrates that the specificity and sensitivity of the combination of PDGFRA IHC (positive PDGFRA expression with dot-like pattern) and GIST histomorphology (epithelioid phenotype) in detecting PDGFRA mutations in GIST in this research study was 100% and 51.02% respectively.
PDGFRA IHC (positive PDGFRA expression) alone did not differentiate GISTs with PDGFRA mutations from other types of GISTs in this research study. However, the combination of PDGFRA IHC (positive PDGFRA expression with dot-like pattern) and GIST histomorphology (epithelioid phenotype) was a very reliable specific predictor of PDGFRA mutations in the GIST based on the findings of this study.

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