- An Analysis of HER-2/neu, ERCC1, and GST-pi in Advanced Non-Small Cell Lung Cancer Patients Who are Treated with Platinum-based Chemotherapy.
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Kyung Jin Seo, Byoung Yong Shim, Hoon Kyo Kim, Ji Han Jung, Jinyoung Yoo, Seok Jin Kang, Kyo Young Lee
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Korean J Pathol. 2008;42(6):327-334.
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 Abstract
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- BACKGROUND
Platinum-based chemotherapy has shown to be an effective first-line treatment for patients with advanced stage, unresectable non-small cell lung cancer (NSCLC). We evaluated the response rate to combination chemotherapy with cisplatin and taxane, and the significance of the HER-2/neu, ERCC1, and GST-pi status as predictive markers for the tumor response. METHODS: The HER-2/neu, ERCC1, and GST-pi status were analyzed in the biopsy specimens obtained from 35 patients with advanced stage NSCLC prior to cisplatin plus either paclitaxel or docetaxel chemotherapy. RESULTS: The response rate of the tumors to combination chemotherapy was 62.9% (22/35). HER-2/neu was amplified in 51.4% (18/35) of the tumors, and this was observed exclusively in patients with progressive disease (p=0.014). ERCC1 was overexpressed in 77.2% of the specimens (27/35), and this showed a tendency to correlate with the tumor response (p=0.057).
GST-pi was detected in 85.7% of the specimens (30/35).
Seventy-seven percent of the patients with a negative HER-2/neu and positive ERCC1 status showed a partial response, which was in contrast to only a 25% response rate for the patients with a positive HER-2/neu and negative ERCC1 status (p=0.006). The overall survival was prolonged in the patients without HER-2/neu amplification (15 vs 8.5 months, respectively, p=0.008). On multivariate analysis, the HER-2/neu status remained the significant predictor of survival (p=0.005). CONCLUSIONS: A combination of the ERCC1, HER-2/neu status may define a subset of patients with the most favorable response to combination chemotherapy regimens for treating advanced NSCLC.
- Protein Expression and Gene Amplification of Epidermal Growth Factor Receptor in Non-Small Cell Lung Cancer: Correlation with the Response to Gefitinib Therapy.
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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
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Korean J Pathol. 2008;42(1):1-8.
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Abstract
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- 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.
- Expression of Thymidylate Synthase in Non-Small Cell Lung Cancer.
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Jinyoung Yoo, Suzi Kim, Byoung Yong Shim, Sung Hwan Kim, So Hyang Song, Deog Gon Cho, Meyung Im Ahn, Chi Hong Kim, Kyu Do Cho, Seok Jin Kang, Hoon Kyo Kim
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Korean J Pathol. 2005;39(6):412-417.
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Abstract
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- BACKGROUND
Thymidylate synthase (TS) catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), and this is an essential step in DNA biosynthesis. The present investigation was designed to determine the expression of TS in the patients with non-small cell lung cancer (NSCLC) and to assess the possible associations between the TS status and the p53 or proliferative index (PI).
METHODS
The archival tumor tissues from 56 previously untreated NSCLC patients were examined by immunohistochemistry for TS, p53 and Ki-67.
RESULTS
Forty-one men and 15 women (age range: 35 to 79 years, mean age: 62 years) were included in this study. The TS expression was high in 40 patients (71.4%) and low in 16 patients (28.6%). The aberrant expression of p53 was detected in 35 patients (62.5%). The mean PI for all the patients was 31.4+/-12.1. The TS-high tumors tended to be more poorly differentiated (p=0.069). The TS expression by a semiquantitative fourscale grading system was significantly correlated with the PIs (p=0.003). No correlation was established between the TS expression and the p53 status (p=0.806) or survival (p=0.951). CONCLUSIONS: TS was not confirmed to be a useful marker for determining the prognosis of NSCLC patients. However, our data suggest that the tumor cells with higher TS expression have a higher proliferative activity.
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