Prognostic value of ERCC1, RRM1, and TS proteins in patients with resected non-small cell lung cancer.

PURPOSE: Recent clinical trials showed that expression of excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M1 (RRM1), and thymidylate synthase (TS) proteins was able to predict the effects of non-small cell lung cancer (NSCLC) to chemotherapy. However, it remains unknown whether the adjuvant chemotherapy based on expression of the three proteins has survival significance in Chinese NSCLC patients. METHODS: We investigated 128 Chinese patients receiving chemotherapy after tumor resection for expression of these proteins using immunohistochemistry. Based on protein expression, patients were assigned to two groups for different adjuvant chemotherapy regimes. The disease-free survival (DFS) data were collected and analyzed using Kaplan-Meier curves and Cox models. RESULTS: We found that DFS of these patients with carboplatin and a third-generation agent (gemcitabine or pemetrexed) stratified by protein expression showed no statistical difference between individual treatment versus non-individuation treatment analyzed using Kaplan-Meier method (P = 0.143, median 23.9 vs. 30.8 months). Furthermore, the multivariate analysis showed that histology and tumor stages were independent predictors for DFS in these patients. CONCLUSIONS: The results suggest that chemotherapy based on ERCC1, RRM1, and TS expression did not have significant impact on DFS of patients with resection of NSCLC.

[EGFR gene copy number, ERCC1 and BRCA1 protein expression and their relationship in non-small cell lung cancer].

OBJECTIVE: To evaluate the expression of epidermal growth factor receptor (EGFR) gene copy number and the expression of ERCC1 and BRCA1 proteins in patients with non-small-cell lung cancer (NSCLC) and the correlation between them. METHODS: The status of EGFR gene copy number was determined by in situ hybridization (FISH), and the expression of ERCC1 and BRCC1 proteins was examined by immunohistochemistry (IHC). The relationship of EGFR gene copy number with the expression of ERCC1 and BRCA1 and the clinical pathologic features were analyzed. RESULTS: FISH-positive EGFR expression was identified in 40 of 166 samples (24.1%). More FISH-positive EGFR in the female than male patients (31.9% vs. 18.6%, P = 0.048), and non-smoker than smoker (32.8% vs. 16.7%, P = 0.045). FISH-positive EGFR was not associated with age, pathological type, clinical stage and metestasis status (P > 0.05). The expression of ERCC1 protein was identified in 60 of 132 samples (45.5%). The expression of ERCC1 protein varied significantly in tumors of different pathological types (P = 0.046), but not associated with age, gender, clinical stage, metestatic status and smoking status (P > 0.05). The expression of BRCA1 protein was identified in 46 of 131 samples (35.1%). The expression of BRCA1 was not associated with age gender, pathological type, clinical stage, metestatic ststus and smoking status (P > 0.05). There was a moderate correlation between the expressions of ERCC1 and BRCA1 (r = 0.449, P < 0.001), but EGFR gene copy number was not correlated with the expression of ERCC1 or BRCA1 protein. CONCLUSIONS: FISH-positive EGFR expression is associated with gender and smoking status, but not correlated with the expression of ERCC1 and BRCA1 proteins. There is a moderate correlation between the expressions of ERCC1 and BRCA1.

Establishment and characterization of a new drug surviving cell line Am1010, derived directly from muscle metastases of a human lung adenocarcinoma patient with multi-drug-resistance to cisplatin, taxol, and gefitinib.

AIM: To Characterize a new human lung cancer cell line Am1010, derived from drug-surviving cells (DSCs). METHODS: The Am1010 cell line was established after 4 cycles of chemotherapy from an arm muscle metastatic tumor of a patient diagnosed with lung adenocarcinoma. The cell line has been remained in continuous culture for more than one year during this study. RESULTS: The Am1010 cell line demonstrated in vitro multi-drug-resistance to cisplatin, taxol, and gefitinib. The Am1010 cell doubling time without drug treatment was 42.395 h. The IC(50) value of cisplatin was 4.299 micromol/L and >10 micromol/L for the Am1010 and P0318 (a cell line derived from non-DSCs) cells, respectively. The IC(50) value of taxol was 0.067 micromol/L and >1 micromol/L for the Am1010 and P0318 cells, respectively. The IC(50) value of gefitinib was 15.233 micromol/L and >70 micromol/L for Am1010 and P0318 cells, respectively. 11 genes involved in the focal adhesion and cell adhesion pathways were found to be differentially expressed. The cells of Am1010 have a significantly larger chromosome number than most lung cancer cell lines. CONCLUSION: This novel DSCs derived lung cancer cell line will be a valuable in vitro tool for the investigation of lung cancer drug resistance and metastasis.