Abstract 5362: Molecular subtyping and tumor markers in the outcome of Korean advanced/metastatic gastric cancer
Authors: Jii Bum Lee, Sun Young Rha, Woo Sun Kwon, Sejung Park, Hyun Cheol Chung
Journal: Cancer Research (2018)

Abstract Much attention has been focused on utilizing targeted next-generation sequencing and to comprehensively characterize molecular profiles of gastric cancer (GC) adjunct to histopathology. In Asia, many of GC patients are diffuse type and classified as genome stable tumors, but limited efforts have been done to further investigate this specific subtype of cancer. Further assessment according to molecular subtypes is necessary to predict the outcome and determine the proper treatment of advanced/metastatic gastric cancer. Using targeted sequencing with 375 genes based on illumine platform, we divided 147 advanced/metastatic GC patients according to their molecular subtypes (EBV infected tumors (n=3, 2.0%), MSI tumors (n=3, 2.0%), chromosomally instable tumors (CIN, n=47, 32.0%), genomically stable tumors (GS, n=94, 64.0%) and level of CEA and CA 19-9 (cut off values &amp;lt;5 and &amp;lt;37 U/dL, respectively). Tumor specimens were subjected to GC specific histopathology panels to confirm genetic variations [EBV encoding RNA in-situ hybridization, IHC for mismatch repair proteins (ML1, MSH2, MSH6, PMS2), receptor tyrosine kinase (HER2, EGFR, C-met), and PTEN]. OS and PFS were calculated twice, corresponding to the respective 1st or 2nd line chemotherapy. Results show that there was no difference in OS, PFS among the molecular subgroups. Overall, there were no differences in tumor markers (CEA, CA 19-9) in relationship to molecular subtypes (p=0.254, 0.387, respectively). When CIN and GS tumors were further subdivided according to the level of tumor markers, CIN tumors expressing either CEA or CA 19-9 had the longest PFS2 (time from 2nd line chemotherapy until death), while both expression of CEA/CA 19-9 had the shortest PFS [p= 0.040; (median PFS of both positive, both negative, and either one positive tumor markers were 2.6, 3.7, 6.3 months, respectively)]. Amplification of RTKs were detected in a mutually exclusive pattern, and RTKs were amplified in 22 cases [ERBB2 (n=10), FGFR2 (n=4), EGFR (n=3), MET (n=2), ERBB3 (n=1), FGFR3 (n=1), IGF1R (n=1). ERBB4, FGFR1, FGFR4 were not amplified. In addition, 50 actionable (druggable) mutations and CNVs (copy number variations) were identified [EBV (n=1, 33.3%), MSI (n=2, 66.7%), CIN (n=22, 46.8%), GS (n=25, 26.6%)]. CIN tumors had more CNVs (13/22) while GS tumors had more mutations (23/25). In contrast with TGGA data, Korean GS tumors showed significant proportion of druggable targets than expected. In conclusion, genomic and molecular profiling is not prognostic but might be useful in conjunction with clinical parameters such as tumor markers. Moreover, we suggest genomic information could guide the proper treatment selection of advanced and metastatic GC. Citation Format: Jii Bum Lee, Sun Young Rha, Woo Sun Kwon, Sejung Park, Hyun Cheol Chung. Molecular subtyping and tumor markers in the outcome of Korean advanced/metastatic gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5362.