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Published on: December 5, 2017
A comparative study of gastric adenocarcinoma HER2 IHC phenotype and mass spectrometry-based quantification
Bin Xu1, Hui Chen2, Jingjing Zhang3
1Pathology Department, Fushun Central Hospital, Fushun, Liaoning, China.
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/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.
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.
Insights
A new mass spectrometry method accurately quantifies HER2 protein in gastric cancer tissues, overcoming limitations of current tests like IHC and FISH. This offers potential as a companion diagnostic for anti-HER2 therapies.
Area of Science:
- Oncology
- Biochemistry
- Analytical Chemistry
Background:
- Gastric cancer is a heterogeneous malignancy.
- Anti-HER2 therapy improves outcomes in HER2-overexpressing cases.
- Current HER2 testing (IHC, FISH) has limitations, yielding discordant results.
Purpose of the Study:
- To introduce and validate a novel HER2 protein detection method using mass spectrometry selected reaction monitoring (MS-SRM).
- To compare MS-SRM with existing methods (IHC, FISH) for HER2 expression analysis in gastric cancer.
Main Methods:
- Retrospective analysis of 118 formalin-fixed paraffin-embedded (FFPE) tissues from advanced gastric adenocarcinoma patients.
- Validation of MS-SRM for HER2 protein quantification.
- Comparison of MS-SRM results with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
Main Results:
- Established detection limits for abnormal HER2 protein expression (300-700 amol/μg).
- Found high HER2 expression correlated with intestinal type features in mixed Lauren subtypes.
- Demonstrated MS-SRM's ability to directly quantify HER2 protein.
Conclusions:
- MS-SRM overcomes IHC limitations, offering direct HER2 protein quantification.
- The MS-SRM method can supplement IHC for HER2 expression analysis.
- MS-SRM shows potential as a companion diagnostic for advanced gastric cancer treatments, pending large-scale validation.
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