Somatic mutations in epidermal growth factor receptor underlying complete responsiveness to gefitinib in a Taiwanese female patient with metastatic adenocarcinoma of lung

Abstract

A 61-year-old never-smoker female suffered from adenocarcinoma of the lung with chest wall invasion and peri-adrenal lymph node metastases. After palliative resection of all clinically detectable primary and metastatic adenocarcinoma, she received cisplatin and gemcitabine combination chemotherapy for a total of 3 cycles. New metastatic lesions were found in spleen and para-aortic lymph nodes. Her tumor tissue was subjected to mutation analysis for epidermal growth factor receptor (EGFR) and had been shown to have a T-->G missense mutation in nucleotide 2819 of EGFR full-length cDNA (accession no. NM_005228.3), within exon 21 of the EGFR gene, resulting in amino acid substitutions from leucine to arginine at codon 858 (L858R) as expected. She received oral gefitinib 250 mg/day after mutation analysis. She had a very good tumor response with more than 90% tumor reduction shown by abdominal computed tomographic scan, normalization of previously elevated carcinoembryonic antigen level, and complete resolution of previous uptake signals in spleen and para-aortic lymph nodes shown by positron emission tomographic scan. She has been kept in clinical complete remission for 11+ months after the initiation of gefitinib treatment. Our patient supports the proposition that somatic mutation L858R in exon 21 of the EGFR gene accounts for complete responsiveness to gefitinib in a Taiwanese female patient with metastatic adenocarcinoma of lung.

Epidermal Growth Factor Receptor Gene in Primary Tumor and Metastatic Sites from Non-small Cell Lung Cancer

“…5 During the last few years, new molecularly targeted agents aimed to inhibit specific pathways and key molecules in tumor growth and progression have been developed. 18 Acquired mutations of EGFR gene in exons 18 to 21 and EGFR gene copy number, which is assessed by fluorescence in situ hybridization (FISH), could be used to predict a patient's responsiveness. 8 Ligand binding to EGFR leads to receptor TK activation and to a series of downstream signaling activation that mediate proliferation, migration, invasion, and suppression of apoptosis.…”

EGFR copy number alterations in primary tumors, metastatic lymph nodes, and recurrent and multiple primary tumors in oral cavity squamous cell carcinoma

“…In non-small cell lung cancer (NSCLC), several reports have also shown that EGFR-specific tyrosine kinase inhibitors, such as gefitinib and erlotinib, are capable of reducing brain and adrenal metastases [ 22 , 23 ]. EGFR mutations, amplifications or gene gains have been associated with clinical responses to those inhibitors [ 18 , 24 ]. A previous study demonstrated that EGFR FISH analysis may be used as an alternative to gene mutation analysis as the primary laboratory test [ 25 ].…”