Cross-testing of major molecular markers indicates distinct pathways of tumorigenesis in gastric adenocarcinomas and synchronous gastrointestinal stromal tumors

• Published in: Scientific reports 2020-12, Vol.10 (1), p.22212-11, Article 22212
• Main Authors: Kocsmár, Éva, Kocsmár, Ildikó, Szalai, Luca, Lendvai, Gábor, Szijártó, Attila, Schaff, Zsuzsa, Kiss, András, Kovalszky, Ilona, Papp, Gergő, Lotz, Gábor
• Format: Article
• Language: English
• Subjects: 692/4020/1503/1504; 692/4020/1503/1504/1829; 692/4028/67/2324; 692/4028/67/68; 692/420/755; Adenocarcinoma; Aged; Biomarkers, Tumor; c-Kit protein; CD34 antigen; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Diagnosis, Differential; Disease Susceptibility; Exons; Female; Gastric cancer; Gastrointestinal cancer; Gastrointestinal Stromal Tumors - diagnosis; Gastrointestinal Stromal Tumors - epidemiology; Gastrointestinal Stromal Tumors - etiology; Genomic instability; Humanities and Social Sciences; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Male; Middle Aged; multidisciplinary; Mutation; Neoplasm Grading; Neoplasm Staging; Neoplasms, Multiple Primary - diagnosis; Neoplasms, Multiple Primary - epidemiology; Neoplasms, Multiple Primary - etiology; Science; Science (multidisciplinary); Stomach Neoplasms - diagnosis; Stomach Neoplasms - epidemiology; Stomach Neoplasms - etiology; Tumorigenesis; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-78232-2

Small subtype of the gastrointestinal stromal tumor (micro-GIST, MG) is usually asymptomatic and is frequently found incidentally in association with gastric adenocarcinoma (GAC). The background of this coincidence is still an open question. This study comprehensively characterized nine MGs and GACs present in the same surgical specimen by cross-testing the markers of the major pathogenetic pathways of both tumor types. All of the MGs were immunohistochemically positive for CD117/KIT, CD34, and DOG1. DOG1 was also detected in four GACs. Four MGs carried mutations in c-KIT (exons 9, 11, and 13) and two cases in PDGFRα (exon 18). None of the GACs carried activating mutations in c-KIT or PDGFRα. MMR immunopanel identified one GAC as microsatellite unstable tumor. No EBV-positive tumor was found. According to the TCGA molecular classification, one GAC was categorized in the MSI subgroup, three GACs in the genomically stable subgroup, and the rest into the chromosomal instability subgroup. Although a common carcinogenic effect cannot be ruled out, our data suggest a distinct molecular background in the evolvement of the synchronous MGs and GACs. The presence of a MG in gastric resection specimens may be indicative of the development of synchronous malignant tumors in or outside the stomach.