Research paperGTF2I mutation frequently occurs in more indolent thymic epithelial tumors and predicts better prognosis

•A known missense mutation in GTF2I was evaluated in a Chinese cohort of patients with thymic epithelioid tumor.•Histological subtype significantly predicted the presence of GTF2I mutation in patients with TETs.•GTF2I mutation correlated with better prognosis in patients with TETs.

ObjectivesA missense mutation in GTF2I was previously identified in thymic epithelioid tumor (TET). However, the clinicopathological relevance of GTF2I mutation has not been illustrated. We studied the prognostic importance of GTF2I mutation as well as its relation to histological subtypes in a large number of TETs.MethodsTET samples from 296 patients with clinical and follow-up data were collected, and histological subtypes were classified. Analysis of the GTF2I (chromosome 7 c.74146970T > A) mutation was undertaken by using quantitative real time polymerase chain reaction (qPCR) and direct sequencing. The association of GTF2I mutation with clinicopathological features as well as prognosis was analyzed.ResultsOne hundred twenty-four out of 296 (41.9%) patients harbored the GTF2I mutation (chromosome 7 c.74146970T > A). GTF2I mutation was observed in 20 (87.0%) cases of type A thymoma, 70 (78.7%) of type AB thymoma, and the frequency decreased with the degree of histological subtype aggressiveness, with the lowest rate in thymic carcinoma (7.7%). The difference of GTF2I mutation distribution in histological subtypes was statistically significant (p < 0.001). The GTF2I mutation was found more frequently in patients with early Masaoka stage (I-II, n = 112, 90.3%) than in those with advanced stage (III-IV) disease (n = 12, 9.6%, p < 0.001). However, only histological subtype significantly predicted the presence of the GTF2I mutation in patients with TETs. The presence of the GTF2I mutation correlated with better prognosis (90.0% compared to 72.0% 5-year survival, and 86% compared to 56% 10-year survival, respectively; log-rank p = 0.001). Moreover, it was an independent prognostic factor [hazard ratio (HR), 0.35; 95% confidential interval (CI), 0.15-0.81; p = 0.014)].ConclusionsThe frequency of the GTF2I mutation is higher in more indolent TETs, and correlates with better prognosis. Further studies are required to elucidate the role of the GTF2I mutation in TETs and its clinical application.