OBJECTIVETo investigate the frequency of EML4-ALK fusion gene in non-small-cell lung cancer (NSCLC) patients, and its correlation with clinicopathologic features.

METHODSReal-time PCR was used to detect the presence of EML4-ALK fusion gene in 268 cases of NSCLCs using paraffin-embedded tissue samples(among which 164 samples were re-validated by Sanger sequencing). Related clinicopathological correlation was analyzed.

RESULTSEML4-ALK fusion gene was found in 4.1% (11/268) of the cases. One hundred and sixty four samples were verified by Sanger sequencing, and the overall coincidence of the results of two methods (Sanger sequencing and Real-time PCR) was 100%. Female patients (5.9%, 5/85), ≤ 60 years of age (4.3%, 6/140), non-smokers (6.8%, 8/118) and adenocarcinomas (7.6%, 10/132) had a higher mutation rate than that in male patients (3.3%, 6/183), > 60 years of age (4.0%, 5/124), smokers (1.6%, 2/132) and squamous cell carcinomas (1.3%, 1/79), although no statistical significance in age (P = 0.918), gender (P = 0.503), smoking history (P = 0.092) and histological type (P = 0.094).

CONCLUSIONSChinese NSCLC patients have a 4.1% detection rate of EML4-ALK fusion gene in the tumor tissues. Female, non-smoker and adenocarcinoma histological subtype tend to be associated with a higher rate of EML4-ALK gene fusion.

Adenocarcinoma ; genetics ; metabolism ; pathology ; surgery ; Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; pathology ; surgery ; Female ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; metabolism ; Sex Factors ; Smoking ; Young Adult

Adenocarcinoma ; genetics ; pathology ; surgery ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; methods ; Bronchoscopy ; Carcinoma, Large Cell ; genetics ; pathology ; surgery ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; surgery ; Carcinoma, Squamous Cell ; genetics ; pathology ; surgery ; Female ; Gene Amplification ; Humans ; Lung Neoplasms ; genetics ; pathology ; surgery ; Male ; Middle Aged ; Polyploidy ; Receptor, Epidermal Growth Factor ; genetics ; Young Adult

This study was aimed to characterize clinicopathological features and prognosis of patients with adenosquamous lung carcinoma (ASC). Among the 2531 patients with lung cancer who underwent surgery between January 2000 and June 2012 in our hospital, 59 were histologically diagnosed as having ASC. The clinicopathological features and follow-up data of ASC patients were collected and analyzed statistically. Superior lobectomy was accomplished in 40 patients, middle and inferior lobectomy in 3, lobectomy plus partial resection of contralateral lung in 5, partial lung resection in 4, and pneumonectomy in 7. Moreover, 22 cases were found to be adenocarcinoma-predominant, and 18 to be squamous cell carcinoma-predominant. The median survival time was 13.6 months, and the 1-, 3-, and 5-year survival rates were 59.9%, 36.4% and 31.2%, respectively. Of the 52 cases with tissue specimens available, 11 had an EGFR mutation (21.2%) and 2 had a KRAS mutation (3.8%). Multivariate analysis showed that histology subtype, pleural invasion, TNM stage, and postoperative treatment were all independent prognostic factors. The data from the current study demonstrated that SCC-predominant histology represents a better prognosis of ASC. Histology subtype, pleural invasion, TNM stage, and postoperative treatment are independent prognostic factors for ASC and adjuvant therapy may help control the disease.
Adult ; Aged ; Carcinoma, Adenosquamous ; genetics ; pathology ; surgery ; Diagnosis, Differential ; Female ; Humans ; Lung Neoplasms ; genetics ; pathology ; surgery ; Male ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras) ; genetics ; Receptor, Epidermal Growth Factor ; genetics ; Retrospective Studies ; Survival Analysis

OBJECTIVESTo investigate the relationship between the epithelial growth factor receptor (EGFR) mutation status and clinicopathological factors, and to analyze the mutation on the effect in non-small cell lung cancer (NSCLC) after surgery.

METHODSThe NSCLC patients who were resected and detected EGFR gene from March 2009 to March 2011 were retrospectively reviewed. The relationship between EGFR mutation status and clinicopathological factors, tumor markers, prognostic was analyzed.

RESULTSThe mutation and the wild group had 169 and 214 patients respectively. EGFR mutation in female, non-smoking, adenocarcinoma and less than 60 years old accounted for 63.91%, 61.54%, 88.76% and 62.13% with statistical significance compared with male (χ(2) = 53.490, P = 0.000), smoking (χ(2) = 48.568, P = 0.000), non-adenocarcinoma (χ(2) = 105.560, P = 0.000) and more than 60 years old (χ(2) = 6.057, P = 0.017). Disease free survival (DFS) of the wild group was better than mutation group (χ(2) = 11.329, P = 0.001). In addition, there were some relations between mutation status and excision repair cross complementing (ERCC1) protein, carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) and Cyfra21-1. ERCC1(+) (χ(2) = 6.739, P = 0.012), SCC(χ(2) = 16.839, P = 0.000) and Cyfra21-1(χ(2) = 6.638, P = 0.013) more than normal value was common in wild group. Increased CEA was common in mutation group (χ(2) = 5.436, P = 0.023).

CONCLUSIONSEGFR mutation is commonly found in female, non-smoking, adenocarcinoma and less than 60 years old NSCLC patients. The wild group obtains better DFS than mutation group. Tumor markers may predict the mutation status, which need further research.

Carcinoma, Non-Small-Cell Lung ; genetics ; mortality ; pathology ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms ; genetics ; pathology ; surgery ; Male ; Middle Aged ; Mutation ; Prognosis ; Receptor, Epidermal Growth Factor ; genetics ; Retrospective Studies

OBJECTIVETo evaluate the possibility of dissemination of lung cancer cells through blood during the operation for lung cancer.

METHODSThe blood samples were taken from 52 patients with non-small cell lung cancer (NSCLC) and 5 patients with benign lung diseases at four different intervals during the operation. The transcription of carcinoembryonic antigen (CEA) messenger ribonucleic acid was assayed by means of nested reverse transcriptase polymerase chain reaction (RT-PCR). A549 (a human adenocarcinoma cell line) served as positive control. The sensitivity has been tested using quantificationally diluted A549 cells.

RESULTSThe CEA mRNA positive rates of all four time spots are as follows: 31% (16/52) at beginning of the operation (sample taken from peripheral vein), 54% (28/52) at ligating the pulmonary vein (peripheral vein), 54% (28/52) at ligating the pulmonary vein (pulmonary vein) and 54% (28/52) at 1 hour after ligating the pulmonary vein (peripheral vein). There is no relationship between the tumor identity and the positive rate of CEA mRNA. The positive rate of CEA mRNA is higher in patients with centrally located lung cancer than that in patients with peripherally located lung cancer, similar phenomenon is also found between patients with advanced lung cancer and the patients with early stage of lung cancer. No negative control samples was found to be positive for CEA mRNA, the sensitivity of our test was 1 x 10(-6).

CONCLUSIONSThe cancer cell dissemination during operation was demonstrated indirectly in our study, the time of pulmonary vein ligation (later or earlier) may affect the quantity of tumor cells released into circulation. Patients with lung cancer of central type and late TNM stage have more possibility of cancer cell dissemination during operation. More effective means may be needed to avoid the dissemination of cancer cells.

Adult ; Aged ; Carcinoembryonic Antigen ; blood ; genetics ; Carcinoma, Non-Small-Cell Lung ; pathology ; surgery ; Female ; Humans ; Lung Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Seeding ; Neoplasm Staging ; Neoplastic Cells, Circulating ; RNA, Messenger ; blood ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity

PURPOSE: Traditional chemotherapy is the main adjuvant therapy for the treatment of non-small cell lung cancer (NSCLC). However, the emergence of multi-drug resistance (MDR) has greatly restricted the curative effect of chemotherapy. Therefore, it is necessary to find a method to treat MDR NSCLC clinically. It is worth investigating whether NSCLCs that are resistant to traditional chemotherapy can be effectively treated with tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR). MATERIALS AND METHODS: The expression of P-glycoprotein (P-gp) and lung resistance-related protein (LRP) was detected by immunohistochemistry, and mutations in EGFR (exons 19 and 21) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (exon 2) were detected by high-resolution melting analysis (HRMA) of surgical NSCLC specimens from 127 patients who did not undergo traditional chemotherapy or radiotherapy. A Pearson chi-square test was performed to analyze the correlations between the expression of P-gp and LRP and mutations in EGFR and KRAS. RESULTS: The expression frequencies of P-gp and LRP were significantly higher in adenocarcinomas from non-smoking patients; the expression frequency of LRP was significantly higher in cancer tissue from female patients. The frequency of EGFR mutations was significantly higher in well to moderately differentiated adenocarcinomas from non-smoking female patients. The frequency of EGFR mutations in the cancers that expressed P-gp, LRP, or both P-gp and LRP was significantly higher than that in cancers that did not express P-gp or LRP. CONCLUSION: NSCLCs expressing P-gp/LRP bear the EGFR mutation in exon 19 or 21 easily.
Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/*genetics/surgery ; Exons/*genetics ; Female ; Humans ; Lung Neoplasms/*genetics/pathology/surgery ; Middle Aged ; Mutation ; P-Glycoprotein/*genetics ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins p21(ras) ; Receptor, Epidermal Growth Factor/*genetics ; Treatment Outcome ; Vault Ribonucleoprotein Particles/*genetics ; ras Proteins/*genetics

Adenocarcinoma ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Adenocarcinoma, Bronchiolo-Alveolar ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Adenocarcinoma, Papillary ; metabolism ; pathology ; Cadherins ; metabolism ; Diagnosis, Differential ; Genes, erbB-1 ; genetics ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Lymphatic Metastasis ; Mucin-1 ; metabolism ; Mutation ; Neoplasm Invasiveness ; beta Catenin ; metabolism

OBJECTIVETo investigate ALK gene rearrangements in lung adenocarcinomas in correlation with clinicopathologic parameters including prognosis.

METHODSFluorescence in situ hybridization (FISH) was used to detect ALK gene rearrangements in 53 cases of lung adenocarcinomas. Mutations in exons 18, 19, 20 and 21 of EGFR were analyzed by Scorpion amplification refractory mutation system (Scorpions ARMS).

RESULTSIn a cohort of 53 lung adenocarcinomas, ALK gene rearrangements were identified in 6 tumors (11.3%), including 4 male and 2 female patients. Five were acinar predominant adenocarcinomas and one was mucinous adenocarcinoma (P=1.000). All tumors with the ALK rearrangements had the wild-type epidermal growth factor receptor (EGFR) gene (P=0.023). The median time of disease-free survival (DFS) in ALK positive patients and negative patients were 14 months (95%CI 8.0-20.0) and 31 months (95%CI 24.9-37.1), respectively and the difference was significant (Log-rank test, P=0.019). ALK gene rearrangements were significantly associated with early recurrence, but not tumor size, pathologic stages, histological differentiation and lymph node metastasis.

CONCLUSIONSALK gene rearrangements are present at a higher frequency in lung adenocarcinomas of the Chinese patients. ALK gene rearrangements are mutually exclusive with EGFR mutations and associated with early tumor recurrence.

Adenocarcinoma, Mucinous ; genetics ; pathology ; surgery ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Acinar Cell ; genetics ; pathology ; surgery ; Disease-Free Survival ; Exons ; Female ; Follow-Up Studies ; Gene Rearrangement ; Humans ; Lung Neoplasms ; genetics ; pathology ; surgery ; Male ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Receptor Protein-Tyrosine Kinases ; genetics ; Receptor, Epidermal Growth Factor ; genetics

OBJECTIVETo investigate the expression of transcription factor SOX4 in lung cancer tissues of female patients in Xuanwei area, Yunnan Province, and explore its correlation with clinicopathological characteristics and prognosis of the female patients.

METHODSReal-time PCR was applied on lung cancer specimens and their corresponding normal lung tissues from 96 female cases of Xuanwei area to assess the expression of SOX4 mRNA. Immunohistochemical staining was performed to investigate the SOX4 protein expression, and further to elucidate its correlation with clinicopathological characteristics and prognosis.

RESULTSThe expression level of SOX4 mRNA in the cancer tissues (2.53 ± 1.65) was significantly higher than that of matched normal tissues (1.43 ± 1.14, P = 0.003). Immunohistochemical staining showed that there were 53.1% (51/96) positive expression of SOX4 protein in the cancer tissue and only 26.0% (25/96) in matched normal tissue (P < 0.001). The expression of SOX4 protein had a significant correlation with clinical stage, lymph node metastasis and differentiation of tumor (P < 0.05). The survival analysis by Kaplan-Meier method showed that patients with positive expression of SOX4 protein, lymph node metastasis and advanced tumor stage had a significantly shorter median survival time (P < 0.05). Cox regression survival analysis showed that pathological grade was a significant independent factor affecting prognosis.

CONCLUSIONSThe expressions of SOX4 mRNA and protein are significantly up-regulated in Xuanwei female lung cancer patients. Patients with positive SOX4 expression have a shorter median survival time. SOX4 protein expression level combined with pathological grade can be used as a prognostic indicator of female lung cancer patients in Xuanwei area, Yunnan Province.

Adenocarcinoma ; genetics ; metabolism ; pathology ; surgery ; Adult ; Aged ; Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; surgery ; China ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; RNA, Messenger ; metabolism ; SOXC Transcription Factors ; genetics ; metabolism ; Survival Rate ; Up-Regulation

OBJECTIVETo investigate the level of ERCC1 mRNA expression in non-small cell lung cancer and analyze the influencing factors of the survival of patients after operation.

METHODSThe level of ERCC1 mRNA expression was quantified in sixty pairs of non-small cell lung cancer tissue and their matched normal lung tissues by real-time PCR assay. The survival of patients was analyzed by univariate Kaplan-Meier and Cox regression analysis.

RESULTSThe level of ERCC1 mRNA expression in cancer tissues (-7.85 ± 3.86) was significantly higher than that in matched normal ones (-11.19 ± 5.03;t = 3.973, P = 0.000). Up-regulation of ERCC1 mRNA was found in 43 of 60 (71.7%) lung cancer tissues compared with that in the matched normal lung tissues (17 of 60, 28.3%). The univariate survival analysis by Kaplan-Meier method showed that the survival rate of patients with high ERCC1 mRNA expression was lower than that in the patients with low expression of ERCC1 mRNA (P = 0.000). Patients with lymph node metastasis, smoking, cancer family history, or high pathological grade had significantly shorter survaival time than those without lymph node metastasis, smoking, cancer family history, or with low pathological grade. Cox regression survival analysis showed that the level of ERCC1 mRNA expression, lymph node metastasis, smoking, and pathological grade were significant independent factors affecting the survival rate.

CONCLUSIONSNon-small cell lung cancer patients with up-regulated ERCC1 expression have a poor survival. The expression of ERCC1 mRNA, lymph node metastasis, pathological grade, cancer family history and smoking can be used as prognostic indicator of non-small cell lung cancer.

Aged ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; pathology ; surgery ; DNA-Binding Proteins ; genetics ; metabolism ; Endonucleases ; genetics ; metabolism ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Proportional Hazards Models ; RNA, Messenger ; metabolism ; Smoking ; adverse effects ; Survival Rate ; Up-Regulation