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Published on: August 11, 2017
Is the epidermal growth factor receptor status in lung cancers reflected in clinicopathologic features?
Kentaro Inamura1, Hironori Ninomiya, Yuichi Ishikawa
1Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
Context:
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are molecular-targeted drugs that are innovatively effective for non-small cell lung carcinomas with EGFR mutations. Epidermal growth factor receptor is a transmembrane receptor forming dimers on ligand binding. These then stimulate signals by activating receptor autophosphorylation through tyrosine kinase activity. Autophosphorylation triggers intracellular pathways facilitating malignant conversion. The most clinically advanced EGFR inhibition strategies include small-molecule inhibition of the intracellular tyrosine kinase domain (gefitinib and erlotinib) and monoclonal antibody-mediated blockade of the extracellular ligand-binding domain (cetuximab). Lung cancers with EGFR mutations are prevalent among patients who are female, of Asian ethnicity, and nonsmokers; thus, they can obtain benefit from EGFR tyrosine kinase inhibitors.
Objective:
To survey histopathologic findings and examine correlations with EGFR mutations. We mainly focused on component cell types (hobnail, columnar, and polygonal) and presence or absence of bronchioloalveolar carcinoma elements and a micropapillary pattern. Although EGFR mutations can be detected by various methods, including polymerase chain reaction-Invader assay or direct sequencing, these are inconvenient.
Data Sources:
Review of the published literature.
Conclusion:
Detailed pathologic examination showed significant genotype-phenotype correlations between EGFR mutations and presence of a bronchioloalveolar carcinoma component, a micropapillary pattern, and the hobnail cell type. We conclude that these characteristic histologic features are good predictors of EGFR mutations, and patients with these features might be good candidates for and could benefit from therapy with EGFR tyrosine kinase inhibitors.
Insights
Histologic features like hobnail cells, bronchioloalveolar carcinoma elements, and micropapillary patterns are strong predictors of EGFR mutations in non-small cell lung cancer. These findings help identify patients who may benefit from EGFR tyrosine kinase inhibitor therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective targeted therapies for non-small cell lung cancer (NSCLC) with specific EGFR mutations.
- EGFR signaling pathways are crucial in cancer development, and inhibition strategies include small-molecule TKIs and monoclonal antibodies.
- Certain patient demographics (female, Asian, non-smoker) are more likely to have EGFR mutations and benefit from TKIs.
Purpose of the Study:
- To investigate the correlation between histopathologic findings in NSCLC and the presence of EGFR mutations.
- To identify specific histological features that can predict EGFR mutation status.
Main Methods:
- A comprehensive review of published literature was conducted.
- Focus was placed on evaluating component cell types (hobnail, columnar, polygonal) and patterns (bronchioloalveolar carcinoma elements, micropapillary pattern).
Main Results:
- Detailed pathologic examination revealed significant genotype-phenotype correlations.
- The presence of bronchioloalveolar carcinoma elements, a micropapillary pattern, and hobnail cell type were strongly associated with EGFR mutations.
Conclusions:
- Characteristic histologic features, including hobnail cells, bronchioloalveolar carcinoma components, and micropapillary patterns, are reliable predictors of EGFR mutations in NSCLC.
- Patients exhibiting these histological features may be ideal candidates for EGFR-TKI therapy and likely to benefit from it.
