Association of the expression of mutant epidermal growth factor receptor protein as determined with mutation-specific antibodies in non-small cell lung cancer with progression-free survival after gefitinib treatment.

Abstract

INTRODUCTION:

Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with an increased response to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib in patients with non-small cell lung cancer (NSCLC). Although most NSCLC patients with EGFR mutations benefit from EGFR-TKI treatment, the efficacy of such treatment varies among individuals. Molecular markers for prediction of EGFR-TKI treatment efficacy in EGFR mutation-positive NSCLC have not been well defined.

METHODS:

The expression of mutant EGFR proteins was quantitated by immunohistochemical analysis with mutation-specific antibodies in tumor specimens from 47 NSCLC patients with postoperative recurrent disease who harbored activating EGFR mutations. The expression score was determined from both the staining intensity and the proportion of tumor tissue expressing the mutant EGFR.

RESULTS:

The median progression-free survival after the start of gefitinib treatment was significantly longer in patients with a high score for mutant EGFR expression than in those with a low score (12.2 versus 3.4 months, p < 0.001), whereas no significant difference in median overall survival was apparent between the two groups (24.9 versus 17.7 months, respectively, p = 0.144). This association between the expression score for mutant EGFR and progression-free survival was apparent both in patients with deletions in exon 19 of EGFR and in those with the L858R mutation in exon 21.

CONCLUSIONS:

Quantitative analysis of mutant EGFR expression by immunohistochemical analysis with mutation-specific antibodies may predict the efficacy of gefitinib treatment for EGFR mutation-positive NSCLC.

• Authors: Koichi Azuma, Isamu Okamoto, Akihiko Kawahara, Tomoki Taira, Kazutaka Nakashima, Satoshi Hattori, Takashi Kinoshita, Masayuki Takeda, Kazuhiko Nakagawa, Shinzo Takamori, Michihiko Kuwano, Mayumi Ono, Masayoshi Kage
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 7 Issue 1 Pg. 122-7 (Jan 2012) ISSN: 1556-1380 [Electronic] United States
• PMID: 21892099 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Protein Kinase Inhibitors
• Quinazolines
• ErbB Receptors
• Gefitinib

Topics

• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, metabolism)
• Disease-Free Survival
• ErbB Receptors (genetics, metabolism)
• Female
• Gefitinib
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, genetics, metabolism)
• Male
• Middle Aged
• Mutation
• Proportional Hazards Models
• Protein Kinase Inhibitors (therapeutic use)
• Quinazolines (therapeutic use)
• Treatment Outcome