کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5716291 1606648 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original contributionClinicopathological 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
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی آسیب‌شناسی و فناوری پزشکی
پیش نمایش صفحه اول مقاله
Original contributionClinicopathological 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
چکیده انگلیسی


- In KIT/PDGFRA wild-type gastrointestinal stromal tumors (wt-GISTs), BRAF mutations occur.
- BRAF mutations are very rare events in wt-GISTs.
- BRAF mutations are regarded as alternative pathogenic event driving tumorigenesis.
- BRAF mutations seem not to have prognostic relevance.
- BRAF inhibition might represent a therapeutic option.

SummaryIn 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Human Pathology - Volume 62, April 2017, Pages 206-214
نویسندگان
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