Universität zu Köln

Huss, Sebastian, Pasternack, Helen, Ihle, Michaela Angelika, Merkelbach-Bruse, Sabine, Heitkoetter, Birthe, Hartmann, Wolfgang ORCID: 0000-0002-7609-5021, Trautmann, Marcel ORCID: 0000-0002-5842-1196, Gevensleben, Heidrun, Buettner, Reinhard, Schildhaus, Hans-Ulrich and Wardelmann, Eva (2017). Clinicopathological and molecular features of a large cohort of gastrointestinal stromal tumors (GISTs) and review of the literature: BRAF mutations in KIT/PDGFRA wild-type GISTs are rare events. Hum. Pathol., 62. S. 206 - 215. PHILADELPHIA: W B SAUNDERS CO-ELSEVIER INC. ISSN 1532-8392

Full text not available from this repository.

Abstract

In KIT/PDGFRA wild-type gastrointestinal stromal tumors (wt-GISTs), BRAF mutations are regarded as alternative pathogenic events driving tumorigenesis. In our study, we aimed at analyzing a large cohort (n = 444) of GISTs for BRAF mutations using molecular and immunohistochemical methods. More than 3000 GIST samples from caucasian patients were available in our GIST and Sarcoma Registry NRW. Of these, we selected 172 wt-GISTs to evaluate the frequency of BRAF mutations. Furthermore, 272 GISTs with a representative KIT and PDGFRA mutational status were selected. BRAF mutational status was evaluated by high-resolution melting analysis, Sanger sequencing, and VE1 immunohistochemistry. A BRAF mutation (p.V600E) was found in 7 cases (3.9%) of the wt-GIST cohort. In 2 cases, multiple synchronous tumors harbored the same somatic BRAF mutation. VE1 immunohistochemical staining had a sensitivity of 81.8% and a specificity of 97.5% to detect BRAF p.V600E mutations. Analyzing our cases and the cases reported in the literature (n = 37), the percentage of intermediate and high-risk BRAF-mutated wt-GISTs (17/31; 54.8%) was comparable to that recorded for large GIST cohorts irrespective of the mutational status. BRAF mutations are rare events in wt-GISTs, and VE1 immunohistochemistry appears to be a valuable pre-screening tool for the detection of BRAF p.V600E mutations. BRAF mutations in GISTs do not seem to have a prognostic value per se. However, as BRAF inhibition represents a therapeutic option to control disease, we suggest the assessment of the BRAF mutational status, especially in the setting of advanced GIST disease. (C) 2017 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Huss, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasternack, Helen UNSPECIFIED UNSPECIFIED UNSPECIFIED Ihle, Michaela Angelika UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Heitkoetter, Birthe UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Wolfgang UNSPECIFIED orcid.org/0000-0002-7609-5021 UNSPECIFIED Trautmann, Marcel UNSPECIFIED orcid.org/0000-0002-5842-1196 UNSPECIFIED Gevensleben, Heidrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Schildhaus, Hans-Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Wardelmann, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-235937
DOI:	10.1016/j.humpath.2017.01.005
Journal or Publication Title:	Hum. Pathol.
Volume:	62
Page Range:	S. 206 - 215
Date:	2017
Publisher:	W B SAUNDERS CO-ELSEVIER INC
Place of Publication:	PHILADELPHIA
ISSN:	1532-8392
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PDGFRA MUTATIONS; GASTRIC TUMORS; IMATINIB-NAIVE; CARNEY TRIAD; FOLLOW-UP; KIT; RESISTANCE; PATHWAY; SUBSET; IMMUNOHISTOCHEMISTRY Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23593