Correlation between serum CEA levels and EGFR mutations in Chinese nonsmokers with lung adenocarcinoma.

AIM: To evaluate the relationship between epidermal growth factor receptor (EGFR) mutations and serum carcinoembryonic antigen (CEA) levels in Chinese nonsmokers with pulmonary adenocarcinoma. METHODS: We sequenced exons 18-21 of the EGFR gene in 98 cases. The patients were divided into two groups based on their pre-treatment serum CEA levels (below or above 5 ng/mL) for analyzing the correlations with EGFR mutations. RESULTS: Sixty-seven cases harbored EGFR mutations. The rates of EGFR mutations and exon 19 mutations in the high-CEA group (78.2% and 49.1%, respectively) were significantly higher those in the low-CEA group (55.8% and 20.9%, respectively). Serum CEA levels were found to be the only independent predictor of EGFR mutation (OR 2.837; 95% CI: 1.178-6.829) and exon 19 mutation (OR 3.618; 95% CI: 1.319-9.918). Furthermore, a higher serum CEA level was associated with a higher EGFR mutation rate and a higher exon 19 mutation rate: patients with serum CEA levels <5 ng/mL, ≥5 and <20 ng/mL, ≥20 ng/mL showed the EGFR mutation rate of 55.8%, 74.1%, 82.1%, respectively, and the exon 19 mutation rate of 20.9%, 40.7%, 57.1%, respectively. Patients with EGFR mutations displayed a significantly higher incidence of abnormal serum CEA levels (>5 ng/mL) than patients without EGFR mutations (64.2% vs 38.7%). CONCLUSION: Elevated serum CEA levels predict the presence of EGFR gene mutations in Chinese nonsmokers with pulmonary adenocarcinoma.

The expression of stem cell-related indicators as a prognostic factor in human lung adenocarcinoma.

INTRODUCTION: The purpose of the present study was to detect the presence of BASC-like stem cell-related indicators, such as clara cell secretory protein (CCSP), Octamer-4 (OCT4) and Bmi-1, and evaluate their implications in the prognosis of patients with lung adenocarcinoma. METHODS: Specimens of 134 cases of lung adenocarcinoma were collected after radical surgery from January 1999 to June 2004. RESULTS: One hundred and twenty-six cases showed cells that were positive for CCSP, 99 cases positive for OCT4, 91 cases simultaneous expression of CCSP and OCT4 and 74 cases positive for Bmi-1. Bmi-1 was significantly higher in patients at stage III compared to patients at stages I and II. The pattern of survival curves showed that Bmi-1 was a significant prognostic factor of poor overall survival in lung adenocarcinoma patients (P = 0.0000), and the patients with OCT4(+) expression showed a greater increase in mortality than OCT4(-) patients (P = 0.0103). The results of univariate and multivariate Cox analysis revealed that the pathological stages of tumor node metastases (P = 0.037), OCT4 (P = 0.046) and Bmi-1 expression (P = 0.001) were independent prognostic factors. CONCLUSIONS: OCT4 and Bmi-1 may be good biomarkers to predict the prognosis of patients with completely resected lung adenocarcinoma.

[Lung adenocarcinoma stem cell phenotypes and their correlation with patient prognosis].

OBJECTIVE: To detect the cancer stem cells and to evaluate their prognostic implication in patients with lung adenocarcinoma. METHODS: Three phenotypic markers of cancer stem cells (SP-C, CCSP and OCT4) in lung adenocarcinoma were detected by immunofluorecence staining. The correlation among the clinicopathological parameters and phenotypes of cancer stem cells as well as survival were analyzed by Cox proportional hazard method. RESULTS: Of the 57 cases, cancer stem cells were detected in 52, including OCT4(+) bronchioloalveolar stem cell (BASC) phenotype (SP-C(+) CCSP(+) OCT4(+)) in 40 cases and OCT4(-) BASC phenotype (SP-C(+) CCSP(+) OCT4(-)) in 12 cases. Statistical analysis revealed that the phenotype of cancer stem cells was related with the cellular differentiation, i.e. the OCT4(+) BASC phenotype occurred more frequently in the well-differentiated tumors, while the OCT4(-) BASC phenotype usually presented in most of the poorly-differentiated ones. Cox analysis showed that the OCT4(+) BASC phenotype was one of prognostic factors. CONCLUSION: The lung adenocarcinoma stem cells have phenotypic features of bronchioalveolar stem cells (SP-C(+) CCSP(+)). The expression of self-renewal regulatory gene OCT4 in these cells indicates an aggressive nature and unfavorable prognosis.

[Analysis of EGFR mutations in 176 cases of non-small cell lung cancer].

OBJECTIVE: To analyze the incidence and profile of mutations in epidermal growth factor receptor (EGFR) in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: A total of 176 cases of NSCLC tissue was enrolled in this study, among which 123 normal lung samples were also included. The tissue DNA was extracted and the EGFR gene in exon 19 to 21 was subjected for PCR amplification and direct sequencing. RESULTS: The EGFR gene in exon 19-21 was of wild type in all normal lung tissues detected. Mutations were found in 57 cases of 176 lung cancer samples, with an incidence of 32. 4%. Mutations were mainly detected in the exon 19 (37/57 cases, 64. 9% ) and exon 21 (18/57 cases, 31. 6% ) , while that in the exon 20 was rare (2/57 cases, 3. 5% ). There were 7 types of EGFR mutation in the exon 19, resulting in the deletion of codon 746 to 753. A missense mutation was detected in exon 20, dealing with codon 789 to 793. The mutation in exon 21 belonged to the single missense substitution in codon 858. The EGFR mutations were more frequent in female patients than male ones, in adenocarcinoma and adenosquamous cell carcinoma versus cancer of other histologies. CONCLUSION: EGFR mutation is a tumor-specific somatic abnormality. Some one third of Chinese NSCLC tumors harbor EGFR mutations, especially in exons 19 and 21. These mutations are more frequently detected in female, adenocarcinoma and adenosquamous cell carcinoma.

[Implication of micrometastatic cancer cells in the peripheral blood on prognosis of non-small cell lung cancer].

OBJECTIVE: To evaluate the relationship of micrometastatic cancer cells in the blood and prognosis of patients with non-small cell lung cancer (NSCLC). METHODS: Blood samples were collected from peripheral vein perioperatively and from the pulmonary vein intraoperatively in NSCLC patients. Cancer cells were detected by flow cytometry, as described previously. The patients were followed up and analyzed statistically. RESULTS: Cancer cells in blood samples were detected in 20 of 58 patients (34.5%). Patients under 57 years of age or with stage III/IV lesions had higher positive findings than those over 57 years or with stage I/II lesions (P = 0.000 and 0.006, respectively). On the basis of 40 month follow-up data, the 2- and 3-year survival rates of patients with positive and negative results were 30.0% vs 20.0%, and 52.6% vs 50.0%, respectively. There was significant difference between the overall survival curves which favored patients with negative findings (P = 0.0291 and 0.0092, respectively). CONCLUSION: This study indicates that cancer cells can be detected in the blood perioperatively from NSCLC patients which means poor prognosis.