Wen-Liang Fang1,2, Ming-Huang Chen2,3, Kuo-Hung Huang1,2, Shih-Ching Chang2,4, Chien-Hsing Lin5, Yee Chao2,3, Su-Shun Lo2,6, Anna Fen-Yau Li2,7, Chew-Wun Wu1,2, Yi-Ming Shyr1,2. 1. Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City 11217, Taiwan. 2. School of Medicine, National Yang-Ming University, Taipei City 11217, Taiwan. 3. Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei City 11217, Taiwan. 4. Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City 11217, Taiwan. 5. Genome Research Center, National Yang-Ming University, Taipei City 11217, Taiwan. 6. Department of Surgery, National Yang-Ming University Hospital, Yilan County 26058, Taiwan. 7. Department of Pathology, Taipei Veterans General Hospital, Taipei City 11217, Taiwan.
Abstract
Background: There has been no report regarding the clinicopathological features and genetic mutations regarding elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in gastric cancer (GC). Methods: The correlation among EMAST status, microsatellite instability (MSI) status, mutations of common GC-related genes and 16 DNA repair-associated genes, and the clinicopathological features were analyzed. Results: Among the 360 GC patients enrolled, there were 76 (21.1%) with EMAST+ tumors and 284 with EMAST- tumors, and 59 (16.4%) were MSI-high (MSI-H) tumors, and 301 were microsatellite stable (MSS) tumors. Patients with EMAST+ tumors exhibited an earlier pathological T category and had more genetic mutations in the PI3K/AKT pathway, ARID1A and DNA repair-associated genes than those with EMAST- tumors. Patients with MSI-H tumors have more genetic mutations in the PI3K/AKT pathway and DNA repair-associated genes than those with MSS tumors. In the subgroup analysis for MSI-H GC, EMAST+ tumors were associated with earlier pathological T and N categories, earlier TNM stages, higher frequency of DNA-repair-associated genetic mutations, and a better survival rate than EMAST- tumors. Conclusions: PI3K/AKT pathway mutations may play an important role in EMAST+ and/or MSI-H GC. EMAST+/MSI-H tumors seem to represent a different subtype of gastric cancer from EMAST-/MSI-H tumors.
Background: There has been no report regarding the clinicopathological features and genetic mutations regarding elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in gastric cancer (GC). Methods: The correlation among EMAST status, microsatellite instability (MSI) status, mutations of common GC-related genes and 16 DNA repair-associated genes, and the clinicopathological features were analyzed. Results: Among the 360 GCpatients enrolled, there were 76 (21.1%) with EMAST+ tumors and 284 with EMAST- tumors, and 59 (16.4%) were MSI-high (MSI-H) tumors, and 301 were microsatellite stable (MSS) tumors. Patients with EMAST+ tumors exhibited an earlier pathological T category and had more genetic mutations in the PI3K/AKT pathway, ARID1A and DNA repair-associated genes than those with EMAST- tumors. Patients with MSI-H tumors have more genetic mutations in the PI3K/AKT pathway and DNA repair-associated genes than those with MSS tumors. In the subgroup analysis for MSI-H GC, EMAST+ tumors were associated with earlier pathological T and N categories, earlier TNM stages, higher frequency of DNA-repair-associated genetic mutations, and a better survival rate than EMAST- tumors. Conclusions: PI3K/AKT pathway mutations may play an important role in EMAST+ and/or MSI-H GC. EMAST+/MSI-H tumors seem to represent a different subtype of gastric cancer from EMAST-/MSI-H tumors.
Authors: Anna-Lina Herz; Sarah Wisser; Meike Kohlruss; Julia Slotta-Huspenina; Moritz Jesinghaus; Bianca Grosser; Katja Steiger; Alexander Novotny; Alexander Hapfelmeier; Thomas Schmidt; Matthias M Gaida; Wilko Weichert; Gisela Keller Journal: J Pathol Clin Res Date: 2022-01-31