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Published on: May 17, 2019
The Visualization of Protein-Protein Interactions in Breast Cancer: Deployment Study in Pathological Examination
Erina Iwabuchi1, Yasuhiro Miki2, Hironobu Sasano1
1Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Abstract:
The therapeutic strategy is determined by protein expression using immunohistochemistry of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) in formalin-fixed paraffin-embedded (FFPE) breast cancer tissues. However, few proteins function independently, and many of them functions due to protein-protein interactions (PPIs) with other proteins. Therefore, it is important to focus on PPIs. This review summarizes the PPIs of ER and HER2 in breast cancer, especially those using a proximity ligation assay that can visualize PPIs in FFPE tissues. In particular, assessing the interaction of CEACAM6 with HER2 may serve as a surrogate marker for the efficacy of trastuzumab in patients with breast cancer. Therefore, in this review, the technique used to detect the interaction of CEACAM6 and HER2 in routinely processed pathological specimens will be applied to the clinical practice of drug selection. We showed the possibility as a novel pathological examination method using PPIs.
Insights
Protein-protein interactions (PPIs) involving estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) are crucial in breast cancer. Visualizing these PPIs, like CEACAM6 with HER2, can guide targeted therapy selection.
Area of Science:
- Oncology
- Molecular Biology
- Biopathology
Background:
- Breast cancer treatment relies on protein expression (ER, PR, HER2) via immunohistochemistry in FFPE tissues.
- Proteins rarely function in isolation; their roles are often defined by protein-protein interactions (PPIs).
- Understanding PPIs is critical for comprehensive breast cancer analysis.
Purpose of the Study:
- To review the protein-protein interactions (PPIs) of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) in breast cancer.
- To highlight the utility of proximity ligation assays for visualizing PPIs in FFPE tissues.
- To explore the potential of CEACAM6-HER2 interactions as a predictive biomarker for trastuzumab efficacy.
Main Methods:
- Review of existing literature on ER and HER2 PPIs in breast cancer.
- Focus on proximity ligation assay (PLA) for detecting PPIs in formalin-fixed paraffin-embedded (FFPE) tissues.
- Discussion of CEACAM6-HER2 interaction detection in pathological specimens.
Main Results:
- Summarized key PPIs involving ER and HER2 in breast cancer.
- Demonstrated the capability of PLA to visualize PPIs in FFPE breast cancer samples.
- Identified CEACAM6-HER2 interaction as a potential surrogate marker for trastuzumab response.
Conclusions:
- PPIs are integral to breast cancer biology and therapeutic strategies.
- Proximity ligation assay offers a novel method for assessing PPIs in clinical pathology.
- Detecting specific PPIs, such as CEACAM6-HER2, can enhance personalized drug selection in breast cancer treatment.
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