Yanfen Feng1, Yiyan Lei2, Xiaoyan Wu3, Yuhua Huang4, Huilan Rao5, Yu Zhang6, Fang Wang7. 1. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, PR China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, PR China. Electronic address: fengyf@sysucc.org.cn. 2. Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510060, PR China. Electronic address: leiyyzsu@126.com. 3. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, PR China; Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, PR China. Electronic address: wuxiaoy@sysucc.org.cn. 4. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, PR China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, PR China. Electronic address: huangyh@sysucc.org.cn. 5. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, PR China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, PR China. Electronic address: raohl@sysucc.org.cn. 6. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, PR China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, PR China. Electronic address: zhangyu@sysucc.org.cn. 7. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, PR China; Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, PR China. Electronic address: wangfang@sysucc.org.cn.
Abstract
OBJECTIVES: A 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. METHODS: TET 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. RESULTS: One 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)]. CONCLUSIONS: The 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.
OBJECTIVES: A 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. METHODS:TET 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. RESULTS: One 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)]. CONCLUSIONS: The 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.
Authors: Magdalena Knetki-Wróblewska; Dariusz M Kowalski; Marta Olszyna-Serementa; Maciej Krzakowski; Małgorzata Szołkowska Journal: Thorac Cancer Date: 2021-01-02 Impact factor: 3.500