Rizzo Francesca Maria, Palmirotta Raffaele, Marzullo Andrea, Resta Nicoletta, Cives Mauro, Tucci Marco, Silvestris Franco
Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro", Piazza Giulio Cesare, 11-70124, Bari, Italy.
University San Raffaele Rome, Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy.
BMC Cancer. 2016 Feb 11;16:87. doi: 10.1186/s12885-016-2111-x.
Gastrointestinal stromal tumors (GISTs) are characterized by mutations of KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or PDGFRA (platelet-derived growth factor receptor α) that may be efficiently targeted by tyrosine kinase inhibitors (TKI). Notwithstanding the early responsiveness to TKI, the majority of GISTs progress, imposing the need for alternative therapeutic strategies. DOG1 (discovered on GIST-1) shows a higher sensitivity as a diagnostic marker than KIT, however its prognostic role has been little investigated.
We evaluated DOG1 expression by immunohistochemistry (IHC) in 59 patients with GISTs, and correlated its levels with clinical and pathological features as well as mutational status. Kaplan-Meier analysis was also applied to assess correlations of the staining score with patient recurrence-free survival (RFS).
DOG1 was expressed in 66% of CD117(+) GISTs and highly associated with tumor size and the rate of wild-type tumors. Kaplan-Meier survival analysis showed that a strong DOG1 expression demonstrated by IHC correlated with a worse 2-year RFS rate, suggesting its potential ability to predict GISTs with poor prognosis.
These findings suggest a prognostic role for DOG1, as well as its potential for inclusion in the criteria for risk stratification.
胃肠道间质瘤（GISTs）的特征是存在KIT（v-kit哈代-朱克曼4型猫肉瘤病毒癌基因同源物）或血小板衍生生长因子受体α（PDGFRA）的突变，酪氨酸激酶抑制剂（TKI）可有效靶向这些突变。尽管对TKI早期有反应，但大多数GISTs仍会进展，因此需要替代治疗策略。DOG1（在GIST-1上发现）作为诊断标志物比KIT具有更高的敏感性，但其预后作用研究较少。
我们通过免疫组织化学（IHC）评估了59例GISTs患者的DOG1表达，并将其水平与临床和病理特征以及突变状态相关联。还应用Kaplan-Meier分析来评估染色评分与患者无复发生存期（RFS）的相关性。
DOG1在66%的CD117(+) GISTs中表达，且与肿瘤大小和野生型肿瘤发生率高度相关。Kaplan-Meier生存分析表明，IHC显示的强DOG1表达与较差的2年RFS率相关，提示其预测预后不良的GISTs的潜在能力。
这些发现提示DOG1具有预后作用，以及将其纳入风险分层标准的潜力。
