title: Multiple sporadic gastrointestinal stromal tumors concomitant with ampullary adenocarcinoma: a case report with KIT and PDGFRA mutational analysis and miR-221/222 expression profile.
abstract: GISTs originating multifocally at different GI sites, in patients lacking familial syndromes, could be interpreted as recurrent/metastatic disease. MiR-221/222 have recently been identified as regulators of KIT expression in GISTs. We report the first case of synchronous GISTs in the stomach and duodenum concomitant with an ampullary adenocarcinoma. Different CD117 expression patterns could be related to different KIT mutational status in the two lesions: gastric GIST showed a dot-like pattern and lacked KIT mutations; duodenal GIST had a strong membranous expression pattern, likely due to KIT exon 9 duplication, which is associated with lower response to imatinib. MiR-221/222 were downregulated in GISTs as compared with normal tissue (p<0.05) and expressed increased levels in the gastric GIST as compared with duodenal one (p<0.05). Our data support an independent origin of the two GISTs. Determining whether these tumors are multiple primaries or recurrencies is helpful to predict their malignancy and to select proper treatment.
authors.affiliation: Surgical Pathology and Cytopathology Unit, Department of Medicine, DIMED University of Padova, Padova, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Blandamura
authors.affiliation: Surgical Pathology and Cytopathology Unit, Department of Medicine, DIMED University of Padova, Padova, Italy. Electronic address: boxlara@tin.it.
authors.forename: Lara
authors.initials: L
authors.lastname: Alessandrini
authors.affiliation: Istituto Oncologico Veneto, IRCCS, Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bertorelle
authors.affiliation: Surgical Pathology and Cytopathology Unit, Department of Medicine, DIMED University of Padova, Padova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonato
authors.affiliation: Surgical Pathology and Cytopathology Unit, Department of Medicine, DIMED University of Padova, Padova, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Guzzardo
authors.affiliation: Surgical Pathology and Cytopathology Unit, Department of Medicine, DIMED University of Padova, Padova, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Valentini
authors.affiliation: Department of Surgical and Gastroenterological Sciences, University of Padova, Padova, Italy.
authors.forename: Imerio
authors.initials: I
authors.lastname: Angriman
authors.affiliation: Surgical Pathology and Cytopathology Unit, Department of Medicine, DIMED University of Padova, Padova, Italy.
authors.forename: Ambrogio
authors.initials: A
authors.lastname: Fassina
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D004252:DNA Mutational Analysis; D004379:Duodenal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005770:Gastrointestinal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D013274:Stomach Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; C525709:MIR221, human; C525710:MIR222, human
keywords: Adenocarcinoma; GISTs; MiR-221/222; Mutation; Polyclonality