OBJECTIVES: To explore the expression of programmed death ligand-1 (PD-L1) as well as the correlation between the expression and the clinicopathological features or prognosis in non-small cell lung cancer (NSCLC). METHODS: The expression of PD-L1 protein in 254 cases of surgically resected lung adenocarcinoma (L-ADC), 228 cases of surgically resected lung squamous cell cancer (L-SCC), and 99 cases of non-cancerous control lung tissues was detected with immunohistochemical SP method. The correlation between the PD-L1 expression and clinicopathological features was analyzed. Kaplan-Meier univariate and Cox multivariate regression analyses were performed to assess the prognosis of patients with L-ADC and L-SCC, respectively. RESULTS: Positive percentage of PD-L1 protein expression was higher in the tissues of L-ADC and L-SCC than that in the non-cancerous control lung tissues respectively (both CONCLUSIONS The positive percentage of PD-L1 protein expression is higher in the L-SCC patients than that in the L-ADC patients. Positive expression of PD-L1 protein can be served as an independent prognostic factor of poor prognosis in the patients with L-ADC.
Adenocarcinoma of Lung ; B7-H1 Antigen/genetics* ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung/surgery* ; Humans ; Lung Neoplasms/surgery* ; Patients ; Prognosis

Significant progress has been made in lung cancer screening, surgery, chemoradiation, targeted therapy, and immunotherapy recently. Surgical resection is the most important treatment for localized non-small cell lung cancer (NSCLC) so far, but there are still many patients who develop local recurrence or distant metastases within 5 years of surgery. Currently, the risk factors of recurrence in patients with NSCLC are mainly based on clinical and pathological features, which hardly identify patients at high risk of recurrence accurately. With the development of new detection technologies, a number of molecular markers that may have a predictive risk of recurrence in NSCLC have been discovered over the years. In order to summarize the molecular markers related to postoperative recurrence in NSCLC patients, we have formulated a consensus on the prediction of postoperative recurrence of NSCLC based on molecular markers. This consensus mainly focuses on the early stage NSCLC patients, discusses and summarizes the risk factors of disease recurrence from the molecular level. It is hoped that more and more valuable information can be provided for the management of patients, so as to provide more guidance for the perioperative management of the patients with early stage NSCLC in the future.
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Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Lung Neoplasms/surgery* ; Consensus ; Early Detection of Cancer ; Neoplasm Staging ; Neoplasm Recurrence, Local/genetics*

Clinical studies have established the clinical application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant targeted therapy. Compared with chemotherapy, the high efficiency and low toxicity of targeted therapy increases the survival benefit of patients. Icotinib was the first EGFR-TKI with independent intellectual property rights in China and the third EGFR-TKI to be marketed in the world. In order to summarize the experience of icotinib and other EGFR-TKIs in the adjuvant treatment of non-small cell lung cancer and further standardize and guide the clinical application of icotinib, experts from the China International Exchange and Promotive Association for Medical and Health Care and the Guangdong Association of Thoracic Diseases have organized an expert consensus on the adjuvant treatment of non-small cell lung cancer with icotinib, which is expected to provide clinicians with evidence-based medical evidences for postoperative targeted drug using.
Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms/surgery* ; Consensus ; Mutation ; ErbB Receptors/genetics* ; Crown Ethers/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

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

OBJECTIVE: To detect the expression of peptidylprolyl cis/trans isomerase NIMA-interacting l (pin1 mRNA) in the circulation of non-small cell lung cancer (NSCLC) and to investigate the effect of ligating pulmonary vein first or ligating pulmonary artery first during operation on haematogenous dissemination of cancer cells. METHODS: Twenty-six consecutive patients with NSCLC who underwent surgical resection with curative intention were randomly assigned into pulmonary artery first-ligation group (PA group) and pulmonary vein first-ligation group (PV group). Blood samples were collected just before and 7 days after the operation. During the lobectomy, blood samples of the proximal part and distal part of the pulmonary vein when it was ligated were collected. Another 10 patients with benign lung disease served as control subjects undergoing surgical resection, and 10 healthy persons served as negative controls. All blood samples were subjected to real-time RT-PCR with pin1 mRNA as the marker. RESULTS: Compared with the benign lung disease and healthy persons, pin1 mRNA in NSCLC was overexpressed (1.45 to approximately 29.86 vs.0.83 to approximately 1.26 vs 1, P<0.05). pin1 mRNA in stage III NSCLC and lymph node positive were significantly higher than in stage I to approximately II and lymph node negative(18.48+/-1.64 vs.10.57+/-1.05, P<0.05;18.93+/-2.10 vs.10.02+/-1.23, P<0.05). Expression of pin1 mRNA in the distal part of the pulmonary vein was significantly higher than that of the proximal part (30.56+/-1.37 vs.20.31+/-1.48, P<0.05); the expression 7 days after the operation was significantly lower than that of preoperation (20.68+/-1.17 vs.29.43+/-2.62, P<0.05). There was no significant difference between the PA group and PV group (9.95+/-0.91 vs.14.71+/-1.64, P>0.05; 16.84+/-2.36 vs.13.36+/-1.78, P>0.05). CONCLUSION pin1 mRNA was overexpressed in the circulation of NSCLC. Ligation of pulmonary vein before the ligation of the pulmonary artery may decrease the expression of pin1 mRNA in the circulation, which can prevent the release of tumor cells into the bloodstream.
Carcinoma, Non-Small-Cell Lung ; blood ; surgery ; Female ; Humans ; Ligation ; methods ; Lung Neoplasms ; blood ; surgery ; Male ; NIMA-Interacting Peptidylprolyl Isomerase ; Peptidylprolyl Isomerase ; genetics ; metabolism ; Pulmonary Artery ; surgery ; Pulmonary Surgical Procedures ; methods ; Pulmonary Veins ; surgery ; RNA, Messenger ; genetics ; metabolism

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

OBJECTIVE: To determine the relation between the promoter methylation status of RUNX3 gene and clinicopathological parameters, prognosis of non-small cell lung cancer (NSCLC). METHODS: We collected 80 formalin-fixed paraffin-embedded lung cancer tissue samples from NSCLC patients who received postoperative adjuvant chemotherapy with cisplatin. Genomic DNA was extracted through phenol/chloroform extraction. The methylation status of RUNX3 was determined by nested methylation-specific PCR (nMSP). We investigated the pathological and prognostic characteristics of NSCLC stratified by methylation status. RESULTS: The RUNX3 promoter methylation was observed in 20 of the 80 NSCLC samples (25.0%). Methylation of RUNX3 was more frequent in adenocarcinomas (36%) than in squamous cell carcinomas (11%) (P=0.020). In multivariate Logistic regression, positive RUNX3 methylation status (P=0.011) was found to be independent disease-free survival factor as was N stage (P<0.001). Kaplan-Meier curves showed patients with RUNX3 methylation had a significantly poorer overall survival than those without methylation (P=0.003; log-rank test). In multivariate Cox proportional hazards regression analysis, RUNX3 methylation (RR:2.345, 95% CI:1.30-4.865, P=0.022) was a significant independent prognostic factor for the overall survival. CONCLUSION RUNX3 methylation is a significant independent prognostic factor for disease-free survival and overall survival.
Aged ; Carcinoma, Non-Small-Cell Lung ; genetics ; surgery ; Core Binding Factor Alpha 3 Subunit ; genetics ; DNA Methylation ; Female ; Humans ; Lung Neoplasms ; genetics ; surgery ; Male ; Middle Aged ; Prognosis ; Promoter Regions, Genetic ; genetics ; Proportional Hazards Models ; Time Factors

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