Prognostic relevance of miRNA let-7e in localized intestinal GIST: A Spanish Group for Research on Sarcoma (GEIS) Study.
2015; Lippincott Williams & Wilkins; Volume: 33; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2015.33.15_suppl.10524
ISSN1527-7755
AutoresJavier Martín‐Broto, Antonio Fernández‐Serra, José Durán, Sílvia Calabuig-Fariñas, Antonio Gutiérrez, Irene Felipe‐Abrio, Dolors Sánchez-Izquierdo, Javier Martínez‐Trufero, Antonio Casado, Andrés Poveda, Luis R. Martinez, Carmen Balañá, Ferrán Losa, Claudia Valverde, Jordi Rubió‐Casadevall, Josefina Cruz, Luis Miguel Gonzalez de Sande, Cristina Tous, Ricardo Cubedo, José Antonio López‐Guerrero,
Tópico(s)Metastasis and carcinoma case studies
Resumo10524 Background: Risk estimation of recurrence in localized GIST relies on factors as mitosis, size, site or capsule rupture. Recently, genotype has shown to add prognostic value at least in intermediate risk group. Nevertheless, there is a remarkable lack of molecular prognostic variables in localized GIST. We had previously performed miRNA arrays in a subset of localized intestinal GIST comparing relapsed vs no-relapsed patients. We identified let-7e (FC = – 1163.9; p < 0.0001) and miR-550 (FC = +204.2; p < 0.0001) as the most significantly downregulated and upregulated miRNAs respectively. Here we analyze the prognostic role of these miRNA in a validation set (VS) of intestinal GIST Methods: Selection criteria used for VS were intestinal GIST, R0 surgery, no tumor rupture, no adjuvant imatinib and size larger than 2 cm. RNA extraction was performed using the RecoverAll Total RNA Extraction kit (Ambion). The expression of miRNAs was determined by means qRT-PCR using specific Taq-Man probes. let-7e and miR-550 expression levels were categorized as above or below median values. Kaplan–Meier and log-rank test were the statistics used and relapse free survival (RFS) was the clinical endpoint Results: A subset of 112 patients was selected as VS, 23 of which were excluded (metastatic, tumor rupture, etc). Thus, 89 patients were selected, 58 of whom recurred after median follow of 117 months. Median of size and mitoses were 10 cm and 10 x50hpf. In univariate analyses, let-7e showed statistically significant difference in median of RFS: 26 (19.5-32.6) vs 50 (24.6-39.7) months for below and above median values respectively (p = 0.011). For miR-550 no significant differences were seen 35 vs 29 months (p = 0.99). Mitosis ≤ 5/ > 5 with 162 vs 26 months (p = 0.002) and size ≤ 10/ > 10 with 37 vs 29 months (p = 0.05) showed also prognostic relevance. In multivariate analysis, mitosis HR 2.7 (1.4-5.3; p = 0.004) and let-7e HR 2.1 (1.2-3.8, p = 0.009) were independent prognostic factors for RFS Conclusions: miRNA let 7-e has demonstrated to be a relevant prognostic factor for RFS in intestinal GIST patients and deserves to be explored for targeting purposes. A further analysis is planned in a larger series of GIST including also gastric cases
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