The usefulness of mutation-specific antibodies in detecting epidermal growth factor receptor mutations and in predicting response to tyrosine kinase inhibitor therapy in lung adenocarcinoma.

Abstract

INTRODUCTION:

Among the mutations of epidermal growth factor receptor (EGFR), deletions in exon 19 (DEL), and point mutations in exon 21 (L858R) predict the response to EGFR-tyrosine kinase inhibitors (TKIs) in primary lung adenocarcinoma. The ability to detecting such mutations using immunohistochemistry (IHC) would be advantageous.

METHODS:

The molecular-based and IHC-based EGFR mutations were analyzed in 577 lung adenocarcinomas using high resolution melting analysis (HRMA) and 2 mutation-specific antibodies, respectively.

RESULTS:

In the molecular-based analyses, DEL was detected in 135 cases (23%), and L858R was detected in 172 cases (30%). In the IHC-based analyses, a positive reaction was detected in 59 cases (10%) for the DEL-specific antibody, and in 139 cases (24%) for the L858R-specific antibody. With the molecular-based results set as the gold standard, the sensitivity and specificity of the DEL-specific antibody were 42.2% and 99.5%, respectively, while the sensitivity and specificity of the L858R-specific antibody were 75.6% and 97.8%, respectively. The antibody specificities improved when the threshold for the mutation-positive reactions was set as >50% of immunopositive tumor cells. The significant predictors of the clinical response to EGFR-TKI were molecular-based EGFR mutations (p<0.001) and IHC-based EGFR mutations (p=0.001). However, a multivariate analysis revealed that only molecular-based EGFR mutations were significantly correlated with the clinical response (p<0.001).

CONCLUSIONS:

Mutation-specific antibodies demonstrated extremely high specificities, but their sensitivities were not higher than those of molecular-based analyses. However, IHC should be performed before a molecular-based analysis, because it is more cost-effective and can effectively select candidates for EGFR-TKI therapy.

• Authors: Yoshiki Kozu, Koji Tsuta, Takashi Kohno, Ikuo Sekine, Akihiko Yoshida, Shunichi Watanabe, Tomohide Tamura, Jun Yokota, Kenji Suzuki, Hisao Asamura, Koh Furuta, Hitoshi Tsuda
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 73 Issue 1 Pg. 45-50 (Jul 2011) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 21129809 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Quinazolines
• ErbB Receptors
• Gefitinib

Topics

• Adenocarcinoma (diagnosis, drug therapy, genetics)
• Adenocarcinoma of Lung
• Adult
• Aged
• Aged, 80 and over
• Antibody Specificity
• ErbB Receptors (antagonists & inhibitors, genetics)
• Female
• Gefitinib
• Genetic Association Studies
• Humans
• Immunohistochemistry
• Lung Neoplasms (diagnosis, drug therapy, genetics)
• Male
• Middle Aged
• Multivariate Analysis
• Point Mutation
• Quinazolines (therapeutic use)
• Sequence Deletion