Tumor Genotype Is an Independent Prognostic Factor in Primary Gastrointestinal Stromal Tumors of Gastric Origin: A European Multicenter Analysis Based on ConticaGIST
| Autor: | Janusz Limon, Eva Wardelmann, Elżbieta Bylina, Maria Debiec-Rychter, Patrick Schöffski, Piotr Rutkowski, Isabelle Hostein, Jean-Yves Blay, Agnieszka Wozniak, Isabelle Ray-Coquard, Raf Sciot, Jean-Michel Coindre, Axel Le Cesne, Janusz A. Siedlecki, Hans-Ulrich Schildhaus |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Prognostic variable Pathology Receptor Platelet-Derived Growth Factor alpha Mitotic index Genotype Gastrointestinal Stromal Tumors PDGFRA Gene Frequency Internal medicine medicine Humans Registries Aged GiST Proportional hazards model business.industry Stomach Hazard ratio Cancer Exons Middle Aged Prognosis medicine.disease Tumor Burden Europe Proto-Oncogene Proteins c-kit medicine.anatomical_structure Mutation Female Neoplasm Grading business |
| Zdroj: | Clinical Cancer Research. 20:6105-6116 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: Although the mutational status in gastrointestinal stromal tumors (GIST) can predict the response to treatment with tyrosine kinase inhibitors, the role of tumor genotype as a prognostic factor remains controversial. The ConticaGIST study sought to determine the pathologic and molecular factors associated with disease-free survival (DFS) in patients with operable, imatinib-naive GIST. Experimental Design: Clinicopathologic and molecular data from 1,056 patients with localized GIST who underwent surgery with curative intention (R0/R1) and were registered in the European ConticaGIST database were prospectively obtained and reviewed. Risk of tumor recurrence was stratified using the modified NIH criteria. The median follow-up was 52 months. Results: On testing for potential prognostic parameters, the following were associated with inferior DFS on multivariable Cox model analysis: primary nongastric site, size >10 cm, mitotic index >10 mitoses per 50 high power field, and the KIT exon 9 duplication [hazard ratio (HR), 1.47; 95% confidence interval (CI), 0.9–2.5; P = 0.037] and KIT exon 11 deletions involving codons 557 and/or 558 [KITdel-inc557/558; HR, 1.45; 95% CI, 1.0–2.2; P = 0.004]. Conversely, PDGFRA exon 18 mutations were indicators of better prognosis [HR, 0.23; 95% CI, 0.1–0.6; P = 0.002]. KITdel-inc557/558 were an adverse indicator only in GIST localized in the stomach (P < 0.001) but not in tumors with nongastric origin. In gastric GIST, all other mutations presented remarkably superior 5-year DFS. Conclusions: In conclusion, tumor genotype is an independent molecular prognostic variable associated with gastric GIST and should be used for optimizing tailored adjuvant imatinib treatment. Clin Cancer Res; 20(23); 6105–16. ©2014 AACR. |
| Databáze: | OpenAIRE |
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