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Updated: Mar 18, 2026

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
EGFR mutation testing using archival-stained smears in non-small cell lung carcinoma
1Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Objective:
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown benefits regarding progression-free and overall survival in patients whose tumours show EGFR mutations. Most patients' lung cancer is metastatic when detected. Small tissue samples and cytological materials are widely used in diagnosis. The aim of the present study was to compare the EGFR mutation analysis results between cytology, small biopsies and resections.
Methods:
Archival material for EGFR testing was reviewed. Cell blocks and/or stained smears and tissue blocks were used where appropriate. The tumour cell count and percentage were recorded as well as the DNA content. The influence of TTF-1 immunoreactivity on EGFR testing was also investigated.
Results:
The study cohort included 300 unpaired specimens of 84 resections, 83 small biopsies and 133 cytological materials. EGFR mutation rates did not differ significantly for cytology, small biopsy and resections (P > 0.05). The higher tumour cell percentage in FNAs than in exfoliative cytology did not affect the EGFR mutation status. EGFR mutation rates were similar when either slides or cell blocks were used. Cytology slides revealed a higher tumour cell content and DNA concentration than the cell blocks. May-Grünwald-Giemsa (MGG)-stained smears had higher rates of the EGFR mutation than the Papanicolaou (Pap)-stained slides (P < 0.05). Tumours with negative immunoreactivity for TTF-1 are less likely to have an EGFR mutation (P < 0.05).
Conclusions:
Cytological materials can be used successfully for mutation analysis in lung cancer.
Insights
Cytological samples are reliable for epidermal growth factor receptor (EGFR) mutation analysis in lung cancer, matching results from small biopsies and resections. This confirms cytology
Area of Science:
- Oncology
- Molecular Diagnostics
- Pathology
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) improve outcomes for patients with EGFR-mutated lung cancer.
- Lung cancer is often diagnosed at a metastatic stage, necessitating analysis from limited tissue samples.
- Cytological materials and small biopsies are frequently used for diagnosis.
Purpose of the Study:
- To compare the accuracy of EGFR mutation analysis between cytological samples, small biopsies, and resections.
- To evaluate the impact of specimen type and preparation on EGFR mutation detection.
Main Methods:
- Review of archival material from 300 unpaired specimens (84 resections, 83 small biopsies, 133 cytological).
- Analysis of EGFR mutation rates across different sample types and preparation methods (cell blocks, smears).
- Investigation of tumour cell percentage, DNA content, and TTF-1 immunoreactivity influence.
Main Results:
- EGFR mutation rates were comparable across cytology, small biopsies, and resections (P > 0.05).
- Specimen preparation methods (slides vs. cell blocks) and staining techniques (MGG vs. Pap) influenced EGFR mutation detection.
- Negative TTF-1 immunoreactivity was associated with a lower likelihood of EGFR mutation (P < 0.05).
Conclusions:
- Cytological materials are a viable and accurate source for EGFR mutation analysis in lung cancer.
- These findings support the use of cytology for guiding TKI therapy selection.
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