An Na Seo1,2, Byung Woog Kang3,4, Han Ik Bae1,2, Oh Kyoung Kwon5,6, Ki Bum Park6, Seung Soo Lee5,7, Ho Young Chung5,7, Wansik Yu5,6, Seong Woo Jeon8,9, Hyojeung Kang10, Jong Gwang Kim3,4,11. 1. Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. 2. Department of Pathology, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea. 3. Department of Hematology/Oncology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea bwkang@knu.ac.kr jkk21c@knu.ac.kr. 4. Department of Hematology/Oncology, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea. 5. Department of Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. 6. Gastric Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea. 7. Department of Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea. 8. Department of Gastroenterology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. 9. Department of Gastroenterology, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea. 10. College of Pharmacy, Institute of Microorganisms and Research Institute of Pharmaceutical Sciences, Kyunpook National University, Daegu, Republic of Korea. 11. Kyungpook National University Cancer Research Institute, Daegu, Republic of Korea.
Abstract
BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (GC) is known to harbor a significant enrichment of of phosphatidylinositol 4, 5-biphosphate 3- kinase catalytic subunit alpha isoform (PIK3CA). Therefore, this study investigated the clinical relevance and prognostic role of PIK3CA mutations in patients with EBV-GC. MATERIALS AND METHODS: After reviewing 1,318 consecutive cases of surgically resected GC, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. PIK3CA mutations were identified in formalin-fixed and paraffin-embedded surgical specimens from 112 patients with EBV-GC with available tumor tissue samples. Real-time polymerase chain reaction was used to evaluate hot-spot mutations of exons 1, 4, 7, 9, and 20 of PIK3CA. RESULTS: Among the 112 patients, the frequency of PIK3CA mutations was 25.0% (n=28), and among the 28 patients harboring a PIK3CA mutation, most mutations were identified in exon 9 (n=21, 18.8%). The presence of PIK3CA mutation was also correlated with a higher T category (p<0.001) and N category (p<0.001), as well as the presence of perinueral invasion (p<0.001) and venous invasion (p<0.001). In a univariate analysis, PIK3CA mutation showed no association with overall survival (OS) (p=0.184) or disease-free survival (DFS) (p=0.150). Patients harboring exon 9 PIK3CA mutations exhibited a significantly shorter OS (p=0.023) and DFS (p=0.013) than the patients lacking an exon 9 PIK3CA mutation, yet without statistical significance in the multivariate analysis. Notably, exon 9 E542K mutation of PIK3CA was associated with the worst DFS (p=0.011). CONCLUSION: The current data show that PIK3CA mutations appear to play an important role in carcinogenesis and tumor aggressiveness in EBV-GC, and also support the concept that exon 9 mutation of PIK3CA is a prognostic indicator for predicting patient outcomes and a rationale for therapeutic targeting in EBV-GC. Copyright
BACKGROUND:Epstein-Barr virus (EBV)-associated gastric cancer (GC) is known to harbor a significant enrichment of of phosphatidylinositol 4, 5-biphosphate 3- kinase catalytic subunit alpha isoform (PIK3CA). Therefore, this study investigated the clinical relevance and prognostic role of PIK3CA mutations in patients with EBV-GC. MATERIALS AND METHODS: After reviewing 1,318 consecutive cases of surgically resected GC, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. PIK3CA mutations were identified in formalin-fixed and paraffin-embedded surgical specimens from 112 patients with EBV-GC with available tumor tissue samples. Real-time polymerase chain reaction was used to evaluate hot-spot mutations of exons 1, 4, 7, 9, and 20 of PIK3CA. RESULTS: Among the 112 patients, the frequency of PIK3CA mutations was 25.0% (n=28), and among the 28 patients harboring a PIK3CA mutation, most mutations were identified in exon 9 (n=21, 18.8%). The presence of PIK3CA mutation was also correlated with a higher T category (p<0.001) and N category (p<0.001), as well as the presence of perinueral invasion (p<0.001) and venous invasion (p<0.001). In a univariate analysis, PIK3CA mutation showed no association with overall survival (OS) (p=0.184) or disease-free survival (DFS) (p=0.150). Patients harboring exon 9 PIK3CA mutations exhibited a significantly shorter OS (p=0.023) and DFS (p=0.013) than the patients lacking an exon 9 PIK3CA mutation, yet without statistical significance in the multivariate analysis. Notably, exon 9 E542K mutation of PIK3CA was associated with the worst DFS (p=0.011). CONCLUSION: The current data show that PIK3CA mutations appear to play an important role in carcinogenesis and tumor aggressiveness in EBV-GC, and also support the concept that exon 9 mutation of PIK3CA is a prognostic indicator for predicting patient outcomes and a rationale for therapeutic targeting in EBV-GC. Copyright
Authors: Tania Rossi; Michela Palleschi; Davide Angeli; Michela Tebaldi; Giovanni Martinelli; Ivan Vannini; Maurizio Puccetti; Francesco Limarzi; Roberta Maltoni; Giulia Gallerani; Francesco Fabbri Journal: Front Med (Lausanne) Date: 2021-06-24