IJCEP Copyright © 2007-All rights reserved.
Int J Clin Exp Pathol 2013;6(9):1839-1846

Original Article
Value of epithelioid morphology and PDGFRA immunostaining pattern for prediction of
PDGFRA mutated genotype in gastrointestinal stromal tumors (GISTs)

Abbas Agaimy, Claudia Otto, Alexander Braun, Helene Geddert, Inga-Marie Schaefer, Florian Haller

Institute of Pathology, Friedrich Alexander University, Erlangen, Germany; Institute of Pathology, Albert Ludwigs University, Freiburg, Germany;
Institute of Pathology, St. Vincentius Hospital, Karlsruhe, Germany; Institute of Pathology, University Medical Center, Göttingen, Germany
Received July 8, 2013; Accepted July 30, 2013; Epub August 15, 2013; Published September 1, 2013

Abstract: Aims: Genotyping is a prerequisite for tyrosine kinase inhibitor therapy in high risk and malignant GIST. About 10% of GISTs are wild-
type for KIT but carry PDGFRA mutations. Applying the traditional approach, mutation analysis of these cases is associated with higher costs if
all hotspots regions in KIT (exon 9, 11, 13, 17) are performed at first. Our aim was to evaluate the predictive value of a combined
histomorphological-immunohistochemical pattern analysis of PDGFRA-mutated GISTs to efficiently direct KIT and PDGFRA mutation analysis.
Methods: The histomorphology and PDGFRA immunostaining pattern was studied in a test cohort of 26 PDGFRA mutants. This was then
validated on a cohort of 94 surgically resected GISTs with mutations in KIT (n=72), PDGFRA (n=15) or with wild-type status (n=7) on a tissue
microarray. The histological subtype (spindled, epithelioid, mixed), PDGFRA staining pattern (paranuclear dot-like/Golgi, cytoplasmic and/or
membranous), and extent of staining were determined without knowledge of the genotype. The combination of histomorphology and
immunophenotype were used to classify tumors either as PDGFRA- or non-PDGFRA phenotype. Results: PDGFRA-mutated GISTs were
significantly more often epithelioid (p<0.001) and had a higher PDGFRA expression, compared to KIT-mutants (p<0.001). Paranuclear
PDGFRA immunostaining was almost exclusively observed in PDGFRA mutants (p<0.001). The sensitivity and specificity of this combined
histological-immunohistochemical approach to predict the PDGFRA-genotype was 100% and 99%, respectively (p=6x10-16). Conclusion: A
combination of histomorphology and PDGFRA immunostaining is a reliable predictor of PDGFRA genotype in GIST. This approach allows
direct selection of the “gene/exons of relevance” to be analyzed and may help to reduce costs and work load and shorten processing time of
GIST genotyping by mutation analysis. (IJCEP1307017).

Keywords: GIST, PDGFRA, immunohistochemistry, genotype, dot-like

Address correspondence to: Dr. Abbas Agaimy, Institute of Pathology, University Hospital Erlangen, Krankenhausstraße 8-10, 91054
Erlangen, Ger-many. Tel: +49-9131-85-22288; Fax: +49-9131-85-24745; E-mail: abbas.agaimy@uk-erlangen.de