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Published on: August 14, 2018
Including total EGFR staining in scoring improves EGFR mutations detection by mutation-specific antibodies and EGFR
Shang-Gin Wu1, Yih-Leong Chang, Jou-Wei Lin
1Department of Internal Medicine, College of Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan.
Abstract:
Epidermal growth factor receptor (EGFR) is a novel target for therapy in subsets of non-small cell lung cancer, especially adenocarcinoma. Tumors with EGFR mutations showed good response to EGFR tyrosine kinase inhibitors (TKIs). We aimed to identify the discriminating capacity of immunohistochemical (IHC) scoring to detect L858R and E746-A750 deletion mutation in lung adenocarcinoma patients and predict EGFR TKIs response. Patients with surgically resected lung adenocarcinoma were enrolled. EGFR mutation status was genotyped by PCR and direct sequencing. Mutation-specific antibodies for L858R and E746-A750 deletion were used for IHC staining. Receiver operating characteristic (ROC) curves were used to determine the capacity of IHC, including intensity and/or quickscore (Q score), in differentiating L858R and E746-A750 deletion. We enrolled 143 patients during September 2000 to May 2009. Logistic-regression-model-based scoring containing both L858R Q score and total EGFR expression Q score was able to obtain a maximal area under the curve (AUC: 0.891) to differentiate the patients with L858R. Predictive model based on IHC Q score of E746-A750 deletion and IHC intensity of total EGFR expression reached an AUC of 0.969. The predictive model of L858R had a significantly higher AUC than L858R intensity only (p = 0.036). Of the six patients harboring complex EGFR mutations with classical mutation patterns, five had positive IHC staining. For EGFR TKI treated cancer recurrence patients, those with positive mutation-specific antibody IHC staining had better EGFR TKI response (p = 0.008) and longer progression-free survival (p = 0.012) than those without. In conclusion, total EGFR expression should be included in the IHC interpretation of L858R. After adjusting for total EGFR expression, the scoring method decreased the false positive rate and increased diagnostic power. According to the scoring method, the IHC method is useful to predict the clinical outcome and refine personalized therapy.
Insights
Immunohistochemical scoring effectively detects EGFR mutations in lung adenocarcinoma, predicting response to EGFR tyrosine kinase inhibitors (TKIs). Including total EGFR expression improves diagnostic accuracy for personalized lung cancer therapy.
Area of Science:
- Oncology
- Molecular Pathology
- Translational Medicine
Background:
- Epidermal growth factor receptor (EGFR) mutations are key targets for non-small cell lung cancer therapy, particularly in adenocarcinoma.
- EGFR tyrosine kinase inhibitors (TKIs) demonstrate efficacy in tumors with specific EGFR mutations.
Purpose of the Study:
- To evaluate the diagnostic capacity of immunohistochemical (IHC) scoring for detecting L858R and E746-A750 deletion mutations in lung adenocarcinoma.
- To assess the ability of IHC scoring to predict patient response to EGFR TKIs.
Main Methods:
- Genotyping of EGFR mutations (L858R, E746-A750 deletion) using PCR and direct sequencing.
- Immunohistochemical (IHC) staining employing mutation-specific antibodies for L858R and E746-A750 deletion.
- Receiver operating characteristic (ROC) curve analysis to determine the discriminating capacity of IHC intensity and quick scores (Q scores).
Main Results:
- A logistic regression model incorporating L858R Q score and total EGFR expression Q score achieved an AUC of 0.891 for L858R differentiation.
- A predictive model using IHC Q score for E746-A750 deletion and total EGFR expression intensity reached an AUC of 0.969.
- Positive mutation-specific antibody IHC staining correlated with better EGFR TKI response and longer progression-free survival in recurrent cancer patients.
Conclusions:
- Total EGFR expression should be integrated into IHC interpretation for L858R detection to enhance diagnostic power and reduce false positives.
- The refined IHC scoring method is valuable for predicting clinical outcomes and guiding personalized therapy in lung adenocarcinoma.
