EGFR and erbB2 mutation status in Japanese lung cancer patients
| Autor: | Hidefumi Sasaki, Shigeki Shimizu, Minoru Takada, Masaaki Kawahara, Hisaichi Tanaka, Hiroshi Haneda, Katsuhiko Endo, Motoki Yano, Keiji Iuchi, Akihide Matsumura, Yoshitaka Fujii, Eriko Suzuki, Yoshihiro Kobayashi |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Pathology Lung Neoplasms Receptor ErbB-2 DNA Mutational Analysis Molecular Sequence Data Antineoplastic Agents medicine.disease_cause Exon Sex Factors Gefitinib Japan Carcinoma Non-Small-Cell Lung Internal medicine medicine Humans Epidermal growth factor receptor Lung cancer Aged Mutation Lung Base Sequence biology Reverse Transcriptase Polymerase Chain Reaction business.industry Smoking Respiratory disease Genes erbB-2 Middle Aged medicine.disease respiratory tract diseases ErbB Receptors medicine.anatomical_structure biology.protein Adenocarcinoma Female business medicine.drug |
| Zdroj: | International Journal of Cancer. 118:180-184 |
| ISSN: | 1097-0215 0020-7136 |
| Popis: | Much evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Somatic mutations of the EGFR gene were found in about 25–40% of Japanese lung cancer patients. More recently, erbB2 mutations are found in about 4% of European-derived lung cancer patients. We have investigated EGFR and erbB2 mutation status in 95 surgically treated nonsmall cell lung cancer (NSCLC) cases from Nagoya City University Hospital. Seventy-five adenocarcinoma cases were included. The presence or absence of EGFR and ernB2 mutations of kinase domains were analyzed by reverse transcription polymerase chain reaction (RT-PCR) amplifications and direct sequences. We have also investigated erbB2 mutation status in 27 surgically treated NSCLC cases followed by treatment with gefitinib from Kinki-chuo Chest Medical Center. EGFR mutations (CTGfiCGG; L858R) were found from 14 of 95 lung cancer patients. We also detected the deletion 1a-type mutations from 9 patients and deletion 4-type mutations from 6 patients in exon 19. In exon 20, 4 mutations including 2 novel mutations were found. Total EGFR mutations were present in 35 patients (36.8%). These mutation statuses were significantly correlated with gender (women 73.3% vs. men 20%, p < 0.0001), smoking status (never smoker 69.4% vs. smoker 16.9%, p < 0.0001), pathologic subtypes (adenocarcinoma 45.1% vs. nonadenocarcinoma 12.5%, p 5 0.0089) and differentiation status of the lung cancers (well 51% vs. moderately or poorly 18.4%, p 5 0.0021). On the other hand, erbB2 mutation was only found from 1 of 95 patients, at exon 20. This patient was female and a never smoker with adenocarcinoma. This 12 nucleotide insertion mutation (2324–2325 ins ATACGTGATGGC) was located in the exon 20 at kinase domain (775–776 ins YVMA). There was no erbB2 mutation in 27 gefitinib-treated NSCLC patients. In total, we have found only 1 erbB2 mutation from 122 (0.8%) Japanese NSCLC patients. There was a significantly higher erbB2 positive (21/31) ratio in EGFR mutant patients (13/25, 52.0%) compared to EGFR wild-type patients (10/ 62, 16.1%; p 5 0.0247). The NSCLC specimen with erbB2 mutation showed 11 immunoreactivity. The EGFR mutation status might correlate with the clinicopathologic features related to good response to gefitinib, such as gender, smoking history and pathologic subtypes of lung cancers. However, erbB2 mutation is rare from Japanese lung cancer and is of limited value for molecular target therapy. ' 2005 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text