Gastrointestinal stromal tumors (GISTs) and second malignancies A novel sentinel tumor? A monoinstitutional, STROBE-compliant observational analysis

M.G. Rodriquenz, S. Rossi, R. Ricci, M. Martini, Marilena Larocca, Angelo Dipasquale, M. Quirino, Giovanni Schinzari, Michele Basso, Ettore D'Argento, A. Strippoli, C. Barone, A. Cassano

Research output: Contribution to journalArticlepeer-review

Abstract

Several evidences showed that patients with gastrointestinal stromal tumors (GISTs) develop additional malignancies. However, thorough incidence of second tumors remains uncertain as the possibility of a common molecular pathogenesis. A retrospective series of 128 patients with histologically proven GIST treated at our institution was evaluated. Molecular analysis of KIT and PDGFR-a genes was performed in all patients. Following the involvement of KRAS mutation in many tumors' pathogenesis, analysis of KRAS was performed in patients with also second neoplasms. Forty-six out of 128 GIST patients (35.9%) had a second neoplasm. Most second tumors (52%) raised from gastrointestinal tract and 19.6% from genitourinary tract. Benign neoplasms were also included (21.7%). Molecular analysis was available for 29/46 patients with a second tumor: wild-type GISTs (n. 5), exon 11 (n. 16), exon 13 (n. 1), exon 9 (n. 1) KIT mutations, exon 14 PDGFR-a mutation (n. 2) and exon 18 PDGFR-a mutation (n. 4). KIT exon 11 mutations were more frequent between patients who developed a second tumor (P=0.0003). Mutational analysis of KRAS showed a wild-type sequence in all cases. In metachronous cases, the median time interval between GIST and second tumor was 21.5 months. The high frequency of second tumors suggests that an unknown common molecular mechanism might play a role, but it is not likely that KRAS is involved in this common pathogenesis. The short interval between GIST diagnosis and the onset of second neoplasms asks for a careful follow-up, particularly in the first 3 years after diagnosis. © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved.
Original languageEnglish
JournalMedicine (United States)
Volume95
Issue number38
DOIs
Publication statusPublished - 2016

Keywords

  • GIST
  • KIT
  • KRAS
  • PDGFR
  • Second malignancies
  • KRAS protein, human
  • platelet derived growth factor alpha receptor
  • protein p21
  • stem cell factor receptor
  • adult
  • aged
  • dna mutational analysis
  • exon
  • female
  • gastrointestinal stromal tumor
  • gastrointestinal tumor
  • genetics
  • human
  • immunohistochemistry
  • incidence
  • male
  • middle aged
  • mutation
  • Neoplasms, Second Primary
  • pathology
  • polymerase chain reaction
  • retrospective study
  • time factor
  • very elderly
  • young adult
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Mutational Analysis
  • Exons
  • Female
  • Gastrointestinal Neoplasms
  • Gastrointestinal Stromal Tumors
  • Humans
  • Immunohistochemistry
  • Incidence
  • Male
  • Middle Aged
  • Mutation
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogene Proteins p21(ras)
  • Receptor, Platelet-Derived Growth Factor alpha
  • Retrospective Studies
  • Time Factors
  • Young Adult

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