Mutational status of KIT and PDGFRA and expression of PDGFRA are not associated with prognosis after curative resection of primary Gastrointestinal Stromal Tumors (GISTs)

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Alexander Kern - , Department of Visceral, Thoracic and Vascular Surgery (Author)
  • Heike Görgens - , Department of Surgical Research (Author)
  • Dag Daniel Dittert - , Institute of Pathology (Author)
  • Stefan Krüger - , Group practice for human genetics, Department of Surgical Research (Author)
  • Konrad Klaus Richter - , Southland District Health Board (Author)
  • Hans K. Schackert - , Department of Surgical Research (Author)
  • Hans Detlev Saeger - , Department of Visceral, Thoracic and Vascular Surgery (Author)
  • Gustavo Baretton - , Institute of Pathology (Author)
  • Steffen Pistorius - , Department of Visceral, Thoracic and Vascular Surgery (Author)

Abstract

Background: The aim of this study was to investigate if immunohistochemical expression and mutational status of KIT and PDGFRA in GISTs are associated with the clinical course and disease-free survival after curative resection of the primary tumor without adjuvant systemic therapy. Methods: Paraffin-embedded tumor sections of 95 GISTs were analyzed for KIT and PDGFRA expression by immunohistochemistry. PDGFRA expression was judged using a scoring system subdividing tumors in negative/weak and strong immunoreactivity groups. For mutation analysis, exons 9, 10, 11, 13, and 17 of KIT and exons 10, 12, 14, and 18 of PDGFRA were sequenced. Results: Of 95 R0-resected GISTs, 69% showed strong PDGFRA immunoreactivity. Gastric GISTs revealed a significantly higher rate of strong PDGFRA immunoreactivity (P = 0.01) and longer DFS (P = 0.015) than GISTs of the small intestine. KIT mutations were detected in 43 of 63 (68.3%) completely sequenced cases while PDGFRA mutations were identified in 6 cases (10%). In multivariate analysis, neither KIT/PDGFRA expression nor mutational status of KIT or PDGFRA were independent prognostic factors. Only mitotic rate predicted recurrence independently. Conclusion: Our data do not support the notion that expression of PDGFRA or mutations in KIT or PDGFRA are independent prognostic factors after curative resection of primary GIST.

Details

Original languageEnglish
Pages (from-to)59-65
Number of pages7
JournalJournal of surgical oncology
Volume104
Issue number1
Publication statusPublished - 1 Jul 2011
Peer-reviewedYes

External IDs

PubMed 21387320

Keywords

ASJC Scopus subject areas

Keywords

  • Disease-free survival, GIST, KIT, Mutation analysis, PDGFRA