A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantification
IntroductionGastric 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 ex...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-06-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1152895/full |
| _version_ | 1797809662782865408 |
|---|---|
| author | Bin Xu Hui Chen Jingjing Zhang Yanghai Cong Li Ning Limin Chen Yushi Zhang Yong Zhang Zhanchun Song Yuan Meng Lianqi He Wei-li Liao Ying Lu Fengyi Zhao |
| author_facet | Bin Xu Hui Chen Jingjing Zhang Yanghai Cong Li Ning Limin Chen Yushi Zhang Yong Zhang Zhanchun Song Yuan Meng Lianqi He Wei-li Liao Ying Lu Fengyi Zhao |
| author_sort | Bin Xu |
| collection | DOAJ |
| description | IntroductionGastric 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.MethodsIn 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. ResultsWe established and validated the upper and lower detection limits (300-700 amol/μg) 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. DiscussionThis 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. |
| first_indexed | 2024-03-13T06:56:03Z |
| format | Article |
| id | doaj.art-946b1a79e9ce40de9735ce9b1efb6643 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-13T06:56:03Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-946b1a79e9ce40de9735ce9b1efb66432023-06-07T09:53:13ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-06-011310.3389/fonc.2023.11528951152895A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantificationBin Xu0Hui Chen1Jingjing Zhang2Yanghai Cong3Li Ning4Limin Chen5Yushi Zhang6Yong Zhang7Zhanchun Song8Yuan Meng9Lianqi He10Wei-li Liao11Ying Lu12Fengyi Zhao13Pathology Department, Fushun Central Hospital, Fushun, Liaoning, ChinaStomatology Department, Fushun Central Hospital, Fushun, Liaoning, ChinaTechnology Department, Tianjin Yunjian Medical Laboratory Co. Ltd., Tianjin, ChinaTechnology Department, Tianjin Yunjian Medical Laboratory Co. Ltd., Tianjin, ChinaMedical Oncology, Fushun Central Hospital, Fushun, Liaoning, ChinaTechnology Department, Tianjin Yunjian Medical Laboratory Co. Ltd., Tianjin, ChinaTechnology Department, Tianjin Yunjian Medical Laboratory Co. Ltd., Tianjin, ChinaPathology Department, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, ChinaCirculation Department, Fushun Central Hospital, Fushun, Liaoning, ChinaPathology Department, Fushun Central Hospital, Fushun, Liaoning, ChinaCirculation Department, Fushun Central Hospital, Fushun, Liaoning, ChinaResearch and Development Department, mProbe Inc., Palo Alto, CA, United StatesLaboratory Medicine, Fushun Central Hospital, Fushun, Liaoning, ChinaTechnology Department, Tianjin Yunjian Medical Laboratory Co. Ltd., Tianjin, ChinaIntroductionGastric 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.MethodsIn 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. ResultsWe established and validated the upper and lower detection limits (300-700 amol/μg) 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. DiscussionThis 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.https://www.frontiersin.org/articles/10.3389/fonc.2023.1152895/fullgastric cancermixed classificationHER2IHCMS-SRMtypes identification |
| spellingShingle | Bin Xu Hui Chen Jingjing Zhang Yanghai Cong Li Ning Limin Chen Yushi Zhang Yong Zhang Zhanchun Song Yuan Meng Lianqi He Wei-li Liao Ying Lu Fengyi Zhao A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantification Frontiers in Oncology gastric cancer mixed classification HER2 IHC MS-SRM types identification |
| title | A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantification |
| title_full | A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantification |
| title_fullStr | A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantification |
| title_full_unstemmed | A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantification |
| title_short | A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantification |
| title_sort | comparative study of gastric adenocarcinoma her2 ihc phenotype and mass spectrometry based quantification |
| topic | gastric cancer mixed classification HER2 IHC MS-SRM types identification |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1152895/full |
| work_keys_str_mv | AT binxu acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT huichen acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT jingjingzhang acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT yanghaicong acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT lining acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT liminchen acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT yushizhang acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT yongzhang acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT zhanchunsong acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT yuanmeng acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT lianqihe acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT weililiao acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT yinglu acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT fengyizhao acomparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT binxu comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT huichen comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT jingjingzhang comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT yanghaicong comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT lining comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT liminchen comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT yushizhang comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT yongzhang comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT zhanchunsong comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT yuanmeng comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT lianqihe comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT weililiao comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT yinglu comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification AT fengyizhao comparativestudyofgastricadenocarcinomaher2ihcphenotypeandmassspectrometrybasedquantification |