Gefitinib-Sensitive Mutations of the Epidermal Growth Factor Receptor Tyrosine Kinase Domain in Chinese Patients with Non–Small Cell Lung Cancer

Abstract

Purpose: Studies have shown that mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain are associated with response of lung cancer to gefitinib (Iressa, AstraZeneca Corp., Shanghai, China). A higher incidence of EGFR mutation was observed in non^small cell lung cancer (NSCLC) patients of Japanese origin compared with those of American origin. However, no data about such mutations in Chinese patients with NSCLC could be obtained. Methods: Primary NSCLC tissues were obtained for analysis of mutations in exons 18 to 21 of EGFR from a total of 76 patients, of whom 54 did not receive gefitinib therapy and 22 did. PCR products were sequenced directly and mutations were confirmed by an independent PCR and sequence analysis. All types of mutation were cloned and sequenced. Results: A total of 10 types of mutation were found in the series of patients, including two different silent mutations in exon 20 from 11patients. More than half of the silent mutations (6 of 11) in exon 20 coexisted with other mutations. Mutations were more frequent in adenocarcinoma (17 of 35; 48.6%) compared with squamous carcinoma (1 of 19; 5.3%) among untreated patients. Similar mutations were observed in all seven gefitinib-treated patients with partial response, and no mutations were detected in all eight patients with progressive disease (P < 0.001), except two silent mutations. Three mutations were observed in seven patients with stable disease. Conclusions: Mutations in the epidermal growth factor receptor tyrosine kinase domain in lung adenocarcinomas from Chinese patients were more frequent than reported previously in lung adenocarcinomas from American patients. Such mutations were well correlated with tumor response to gefitinib.

Efficacy of gefitinib for non‐adenocarcinoma non‐small‐cell lung cancer patients harboring epidermal growth factor receptor mutations: A pooled analysis of published reports

“…Thirty-three patients with advanced or recurrent non-adenocarcinoma NSCLC who had the somatic EGFR mutations and were treated with gefitinib were selected from 15 reports. (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) Table 1 summarizes the 15 identified clinical reports. The 15 reports included five prospective studies and 10 retrospective studies including four studies using the data of expanded access programs of gefitinib.…”

“…(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) The study included any reports based on the method of DNA isolation from fresh tissue or paraffin-embedded tissue, and the technique used to enhance tumor-derived DNA, which included either microdissection or use of the more sensitive polymerase chain reaction (PCR) amplification techniques. Not all consecutive NSCLC patients were included in the EGFR mutation analysis in every study.…”

Differences in Epidermal Growth Factor Receptor Gene Mutations and Relationship with Clinicopathological Features in NSCLC Between Uygur and Han Ethnic Groups

“…For example, exon 21 mutation predominated in Taiwan, and exon 19 in Guangdong region, but no significant difference was noted between these two exons in Beijing (Huang et al, 2004;Mu et al, 2005;Qin et al, 2005). Through these studies, it was noticeable that studies were mostly from Europe and East Asia, but rarely from Middle East and Middle Asia.…”

The status of KRAS mutations in patients with non-small cell lung cancers from mainland China

“…With the arrival of the molecular target drug EGFR-TKI, the value of KRAS was recognized again as an important signal molecule of EGFR-RAS/MAPK signal transduction pathway. EGFR mutations were common in females, never-smokers, adenocarcinoma patients with NSCLC from East Asia, while not in patients from Western countries (7,8,(31)(32)(33)(34). KRAS mutation frequency was lower in East Asia than in Western countries.…”