PMID- 37350943 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230701 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 13 DP - 2023 TI - A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantification. PG - 1152895 LID - 10.3389/fonc.2023.1152895 [doi] LID - 1152895 AB - INTRODUCTION: Gastric cancer is a highly heterogeneous malignant tumor of the digestive system. Anti-HER2 treatment can inhibit downstream signaling pathways and improve clinical treatment and outcomes in patients with HER2 protein overexpression. Currently, two standard methods for evaluating HER2 expression status are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). However, these low-throughput assays often produce discordant or equivocal results. METHODS: In this study, we presented a new HER2 protein detection method based on mass spectrometry selected reaction monitoring (MS-SRM) and validated the method. We conducted a retrospective study on 118 formalin-fixed paraffin-embedded (FFPE) tissues from patients with advanced gastric adenocarcinoma in northern China, and we compared the MS-SRM results with those from IHC and correlated them with FISH. RESULTS: We established and validated the upper and lower detection limits (300-700 amol/mug) for abnormal HER2 protein expression in advanced gastric cancer. We also found that, among samples with mixed Lauren subtypes, those with a high level of HER2 expression had typical intestinal type features in pathology. DISCUSSION: This study demonstrated that the MS-SRM method can overcome the limitations and deficiencies of IHC, directly quantify the expression of HER2 protein in tumor cells and be used as a supplement to IHC. It has the potential to be used as a companion diagnosis for new drugs used to treat advanced gastric cancer. Large-scale clinical validation is required. CI - Copyright (c) 2023 Xu, Chen, Zhang, Cong, Ning, Chen, Zhang, Zhang, Song, Meng, He, Liao, Lu and Zhao. FAU - Xu, Bin AU - Xu B AD - Pathology Department, Fushun Central Hospital, Fushun, Liaoning, China. FAU - Chen, Hui AU - Chen H AD - Stomatology Department, Fushun Central Hospital, Fushun, Liaoning, China. FAU - Zhang, Jingjing AU - Zhang J AD - Technology Department, Tianjin Yunjian Medical Laboratory Co. Ltd., Tianjin, China. FAU - Cong, Yanghai AU - Cong Y AD - Technology Department, Tianjin Yunjian Medical Laboratory Co. Ltd., Tianjin, China. FAU - Ning, Li AU - Ning L AD - Medical Oncology, Fushun Central Hospital, Fushun, Liaoning, China. FAU - Chen, Limin AU - Chen L AD - Technology Department, Tianjin Yunjian Medical Laboratory Co. Ltd., Tianjin, China. FAU - Zhang, Yushi AU - Zhang Y AD - Technology Department, Tianjin Yunjian Medical Laboratory Co. Ltd., Tianjin, China. FAU - Zhang, Yong AU - Zhang Y AD - Pathology Department, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China. FAU - Song, Zhanchun AU - Song Z AD - Circulation Department, Fushun Central Hospital, Fushun, Liaoning, China. FAU - Meng, Yuan AU - Meng Y AD - Pathology Department, Fushun Central Hospital, Fushun, Liaoning, China. FAU - He, Lianqi AU - He L AD - Circulation Department, Fushun Central Hospital, Fushun, Liaoning, China. FAU - Liao, Wei-Li AU - Liao WL AD - Research and Development Department, mProbe Inc., Palo Alto, CA, United States. FAU - Lu, Ying AU - Lu Y AD - Laboratory Medicine, Fushun Central Hospital, Fushun, Liaoning, China. FAU - Zhao, Fengyi AU - Zhao F AD - Technology Department, Tianjin Yunjian Medical Laboratory Co. Ltd., Tianjin, China. LA - eng PT - Journal Article DEP - 20230607 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC10283037 OTO - NOTNLM OT - HER2 OT - IHC OT - MS-SRM OT - gastric cancer OT - mixed classification OT - types identification COIS- JZ, YC, LC, YuZ and FZ are employees of Tianjin Yunjian Medical Laboratory Co. Ltd., Tianjin, China. WLL is an employee of mProbe Inc., Palo Alto, California, USA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/06/23 13:07 MHDA- 2023/06/23 13:08 PMCR- 2023/01/01 CRDT- 2023/06/23 10:26 PHST- 2023/01/28 00:00 [received] PHST- 2023/04/10 00:00 [accepted] PHST- 2023/06/23 13:08 [medline] PHST- 2023/06/23 13:07 [pubmed] PHST- 2023/06/23 10:26 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2023.1152895 [doi] PST - epublish SO - Front Oncol. 2023 Jun 7;13:1152895. doi: 10.3389/fonc.2023.1152895. eCollection 2023.