[The pathologist and EGFR in 2004: I like you, nor do it]
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Updated: Aug 19, 2026
Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay
Published on: August 14, 2018
Frédérique Penault-Llorca1, Jean-Christophe Sabourin
1Centre Jean Perrin, 58 Rue Montalembert, BP 392, 63011 Clermont-Ferrand Cedex. fpenault@cjp.fr
Abstract:
Epithelial growth factor receptor (EGFR) appears as a key element in carcinogenesis. It displays high levels of expression in some tumor types. Its activation induces cell proliferation, angiogenesis, cell mobility and inhibition of apoptosis. EGFR inhibitors such as monoclonal antibodies or small molecules tyrosine kinase inhibitors have been developed. For EGFR, the diversity of the activation means (amplification, mutation, enhanced transcription, ligands...) leads to technical caveats. Immunohistochemistry appears to be the most appropriate test for clinical use, but standardized assays and scoring systems are mandatory. Pathologists are involved in the selection of patients for a monoclonal antibody based targeted treatment, Erbitux, and numerous standardization efforts are provided. No consensus has been reached, to date, for a scoring system. Whether the EGFR status has to be tested for the selection of patients is a non answered question. The selection of the "right patient for the right treatment" might be through the evaluation of other putative markers involved in resistance. EGFR testing may be required before targeted treatment. An exciting endpoint might be the functional and dynamic evaluation of EGFR and downstream proteins, for patients, before and during treatment. The exact role of the pathologist still have to be accurately determined.
Insights
Epithelial growth factor receptor (EGFR) is crucial in cancer, but its varied activation presents challenges for targeted therapies like Erbitux. Standardized testing is needed to select the right patients for EGFR-inhibitor treatments.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Epithelial growth factor receptor (EGFR) plays a significant role in cancer development, promoting cell proliferation, angiogenesis, and inhibiting apoptosis.
- Overexpression and diverse activation mechanisms of EGFR in tumors necessitate targeted therapeutic strategies.
- EGFR inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have been developed for cancer treatment.
Purpose of the Study:
- To discuss the challenges and considerations in testing for Epithelial growth factor receptor (EGFR) in cancer patients.
- To evaluate the role of Immunohistochemistry (IHC) as a clinical assay for EGFR status.
- To highlight the need for standardization in EGFR testing and scoring systems for targeted therapy selection.
Main Methods:
- Review of current literature on EGFR in carcinogenesis and targeted therapies.
- Discussion of Immunohistochemistry (IHC) as a primary diagnostic tool for EGFR.
- Analysis of standardization efforts and challenges in EGFR assays and scoring.
Main Results:
- EGFR activation mechanisms are diverse, leading to technical challenges in testing.
- Immunohistochemistry (IHC) is the most suitable clinical test for EGFR, but requires standardization.
- No universal consensus exists for EGFR scoring systems, impacting patient selection for treatments like Erbitux.
- The necessity of EGFR testing for patient selection remains an open question, with potential for other resistance markers.
Conclusions:
- Standardized EGFR testing and scoring systems are crucial for effective patient selection in targeted therapy.
- Further research is needed to determine the definitive role of EGFR testing and to explore dynamic functional evaluations.
- The evolving role of pathologists in optimizing targeted cancer treatments requires accurate determination.
