비소세포폐암종에서 EGFR 단백 발현과 유전자 증폭이제피티닙 치료에 미치는 영향 = Protein Expression and Gene Amplification of EpidermalGrowth Factor Receptor in Non-Small Cell Lung Cancer:Correlation with the Response to Gefitinib Therapy

다국어 초록 (Multilingual 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.

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