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The Korean Journal of Pathology 2008;42(1): 1-8.
Protein Expression and Gene Amplification of Epidermal Growth Factor Receptor in Non-Small Cell Lung Cancer: Correlation with the Response to Gefitinib Therapy.
Jinyoung Yoo, Kyungji Lee, Ji Han Jung, Byoung Yong Shim, Sung Hwan Kim, Deog Gon Cho, Myeong Im Ahn, Chi Hong Kim, Kyu Do Cho, Hoon Kyo Kim, Seok Jin Kang
1Department of Pathology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea. sjkang@vincnet.cuk.ac.kr
2Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
3Department of Radiation Oncology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
4Department of Thoracic Surgery, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
5Department of Diagnostic Radiology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
ABSTRACT
BACKGROUND: Gefitinib is an EGFR tyrosine kinase inhibitor that has shown dramatic effectiveness in a subset of non-small cell lung cancer (NSCLC) patients. We evaluated the response rate to gefitinib, and the significance of the EGFR and HER2/neu status as predictive markers of the tumor response. METHODS: The EGFR and HER2/neu protein expressions, as determined by immunohistochemistry (IHC) and gene amplification via chromogenic in situ hybridization (CISH), were analyzed in biopsy specimens from 46 patients with advanced NSCLC. After their failure with the first-line treatment, all the patients had received gefitinib treatment. RESULTS: A partial response (PR) was achieved in 8 patients (17.4%). An EGFR overexpression was detected in 80.4% (37/46) of the tumors, and this was observed exclusively in patients with a PR (100% vs 75.3%, respectively; p=0.076). EGFR gene amplification was present in 47.8% of the tumors (22/46). HER2/neu was overexpressed in 13%(6/46) and it was amplified in 17% (7/46). The overall survival was prolonged in the female patients (p=0.007), and in patients with T1 and T2 disease (p=0.039), adenocarcinoma (p=0.010), a PR (p=0.022), an EGFR IHC+ status (p=0.033), an EGFR IHC+/CISH+ status (p=0.010), or an EGFR+/HER2/neu+ status (p=0.030). On multivariate analysis, gender, T disease and EGFR IHC/CISH remained the significant predictors of survival. CONCLUSIONS: Gefitinib showed a modest effect for the patients with chemotherapy-refractory advanced NSCLC. A combination of EGFR IHC and CISH might be important for identifying those patients who are most likely to benefit from gefitinib therapy.
Key Words: Carcinoma; Non-small cell lung cancer; ZD1839; EGFR; HER2/neu