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Published on: September 20, 2016
Terminal respiratory unit type lung adenocarcinoma is associated with distinctive EGFR immunoreactivity and EGFR
Michael R Peterson1, Zhe Piao, Lyudmila A Bazhenova
1Department of Pathology, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Abstract:
Approximately 10% to 20% of nonsmall cell lung cancer patients respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as gefitinib. Responders are mostly nonsmokers and women with tumors displaying bronchioloalveolar features. Mutations of the tyrosine kinase domain of the EGFR gene have been associated with a clinical response to gefitinib. A recent study reported that the terminal respiratory unit (TRU)-type adenocarcinoma shares the clinical profile and EGFR mutations of gefitinib responders. EGFR immunoreactivity in this context has not been reported in the literature. We performed a detailed immunohistochemical analysis of EGFR expression on 124 consecutive lung resection specimens for malignancy, to survey the EGFR immunoreactivity in lung cancers in general and to correlate EGFR immunoreactivity with EGFR mutations and TRU-type histology. EGFR positivity was seen most frequently in squamous cell carcinomas (77%), followed by TRU-type adenocarcinomas (63%), large cell carcinomas (23%), and non-TRU-type adenocarcinomas (12%). A distinctive basally oriented cytoplasmic positivity was observed exclusively in TRU-type adenocarcinomas. EGFR mutation was identified in 6 of 54 cases studied and all 6 cases were TRU-type adenocarcinomas. Five of six cases with EGFR mutation were positive for EGFR immunostain with the basal cytoplasmic localization. In conclusion, EGFR immunoreactivity with basal cytoplasmic pattern was exclusively seen in TRU-type adenocarcinoma and a subset of these cases was seen with EGFR mutations in the responders to EGFR inhibitor therapy.
Insights
Epidermal growth factor receptor (EGFR) expression and mutations are key in non-small cell lung cancer. Basal cytoplasmic EGFR positivity was exclusively found in terminal respiratory unit (TRU)-type adenocarcinoma, often with EGFR mutations.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Non-small cell lung cancer (NSCLC) treatment involves epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, with variable patient response.
- EGFR mutations are linked to gefitinib response, particularly in non-smokers and women with specific tumor features.
- Terminal respiratory unit (TRU)-type adenocarcinoma shares characteristics with gefitinib responders, but EGFR expression patterns are not well-documented.
Purpose of the Study:
- To investigate epidermal growth factor receptor (EGFR) immunoreactivity across various lung cancer types.
- To correlate EGFR expression patterns with EGFR mutations and terminal respiratory unit (TRU)-type histology.
- To identify potential biomarkers for EGFR inhibitor therapy response.
Main Methods:
- Immunohistochemical analysis of EGFR expression in 124 lung resection specimens.
- Histological classification including identification of TRU-type adenocarcinoma.
- Detection of EGFR mutations in a subset of cases.
Main Results:
- EGFR positivity was highest in squamous cell carcinomas (77%), followed by TRU-type adenocarcinomas (63%).
- A unique basal cytoplasmic EGFR positivity was exclusively observed in TRU-type adenocarcinomas.
- EGFR mutations were found in 6 of 54 cases, all of which were TRU-type adenocarcinomas and showed positive EGFR immunostaining with basal cytoplasmic localization.
Conclusions:
- Basal cytoplasmic EGFR immunoreactivity is a distinctive marker for TRU-type adenocarcinoma.
- This specific EGFR expression pattern is associated with EGFR mutations in a subset of TRU-type adenocarcinomas.
- Findings suggest potential utility of basal cytoplasmic EGFR positivity as a biomarker for predicting response to EGFR inhibitor therapy in NSCLC.
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