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Prognostic impact of COL5A2 and ACVR1B genes in intestinal high risk localized GIST. A Spanish Group for Research on Sarcoma (GEIS) study.

2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês

10.1200/jco.2016.34.15_suppl.e22514

1527-7755

Javier Martín‐Broto, Antonio Fernández‐Serra, Antonio Gutiérrez, Irene Felipe‐Abrio, José Durán, Sílvia Calabuig-Fariñas, Dolors Sánchez-Izquierdo, Nadia Hindi, Andrés Poveda, Regina Alemany, José Antonio López‐Guerrero,

Gastric Cancer Management and Outcomes

e22514 Background: Molecular prognostic factors related to recurrence in localized GIST are still scarce so that this recurrence risk relies on clinical and pathologic factors as mitotic count, size, location and capsule rupture. Our group has previously reported the prognostic relevance for relapse free survival (RFS) of let-7e microRNA in 89 high risk intestinal localized GIST. The median of RFS were 26 (19.5-32.6) vs 50 (24.6-39.7) months for below and above median values of let-7e respectively (p = 0.011). The next step in the research was to identify those let-7e target genes that could play a prognostic role for recurrence in this specific GIST population Methods: A screening of putative let-7e targets with a series of 10 FFPE GIST samples, 4 with relapse and 6 corresponding to no relapse was performed first. Samples using a RT2 Profiler PCR Array of human let-7 (Qiagen) which determines the expression of 84 genes described biological or bionformatically as interesting targets of this miRNA were analysed. This technique is based in a two steps Real Time PCR. Afterwards, gene expression of selected genes was analysed in the large validation series and genes were dichotomized using median value as cut-off. Kaplan–Meier estimations were used for time-to-event variables and the log-rank test was used to compare groups. Relapse free survival was the clinical endpoint Results: The four most upregulated genes found were: CASP3 (Fold Change = 6.93, p = 0.0029), COL5A2 (FC = 5.97 p = 0.015), ACVR1B (FC = 4.97 p = 0.049) and COL3A1 (FC = 4.44 p = 0.039) with a series of 10 FFPE GIST samples. The analysis of these four genes in 64 localized high risk intestinal localized GIST cases (41 relapsed and 23 no relapsed) showed a significant worse RFS if both genes, COL5A2 and ACVR1B, were overexpressed: 26.1 (13.8-38.3) months vs 42.7 (19.3-66.1) months for overexpression of both genes or not respectively, p = 0.031. Conclusions: Overexpression of COL5A2 and ACVR1B have shown to be bad prognostic factors in the context of high risk intestinal localized GIST. Currently we are expanding the analyses in the validation set.