title: Gastrointestinal stromal tumors (GISTs) and second malignancies: A novel "sentinel tumor"? A monoinstitutional, STROBE-compliant observational analysis.
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-α 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-α mutation (n. 2) and exon 18 PDGFR-α 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.
authors.affiliation: Department of Medical Oncology, Istituto Oncologico Veneto, Padova Department of Medical Oncology, Humanitas Clinical and Research Center, Rozzano (MI) Department of Pathology, Catholic University of Sacred Heart, Rome Department of Medical Oncology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Rodriquenz
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ricci
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Mario
authors.initials: M
authors.lastname: Larocca
authors.forename: Angelo
authors.initials: A
authors.lastname: Dipasquale
authors.forename: Michela
authors.initials: M
authors.lastname: Quirino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schinzari
authors.forename: Michele
authors.initials: M
authors.lastname: Basso
authors.forename: Ettore
authors.initials: E
authors.lastname: D'Argento
authors.forename: Antonia
authors.initials: A
authors.lastname: Strippoli
authors.forename: Carlo
authors.initials: C
authors.lastname: Barone
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cassano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: C117307:KRAS protein, human; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D016283:Proto-Oncogene Proteins p21(ras)