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*

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*

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

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

Transglutaminase 2 (TG2), a cross-linking enzyme, is involved in drug resistance and in the constitutive activation of nuclear factor kappa B (NF-kappaB). We investigated the association of non-small cell lung cancer (NSCLC) treatment efficacy with TG2 and NF-kappaB expression in 120 patients: 102 with adenocarcinoma and 18 with other histologic types. All patients underwent surgery; 88 received adjuvant chemotherapy, with 28 receiving platinum-based doublet chemotherapy as first-line treatment and 29 receiving epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Patients' TG2 and NF-kappaB expression values were calculated semiquantitatively. The median TG2 value was 50 (range, 0-300) and the median NF-kappaB value was 20 (range, 0-240). Disease-free survival did not differ between the low- and high-TG2 groups. Among patients who received palliative platinum-based doublet chemotherapy, progression free survival (PFS) was longer in the low-TG2 group than in the high-TG2 group (11.0 vs. 7.0 months; P=0.330). Among those who received EGFR-TKI therapy, PFS was also longer in the low-TG2 group than in the high-TG 2 group (11.0 vs. 2.0 months; P=0.013). Similarly, in EGFR wild-type patients treated with EGFR-TKI, PFS was longer in patients with low TG2 expression (9.0 vs. 2.0 months; P=0.013). TG2 expression levels can predict PFS in patients with NSCLC treated with EGFR-TKI.
Adenocarcinoma/*drug therapy/mortality/surgery ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/surgery ; Disease-Free Survival ; Female ; GTP-Binding Proteins/*biosynthesis ; Humans ; Lung Neoplasms/*drug therapy/mortality/surgery ; Male ; Middle Aged ; NF-kappa B/biosynthesis ; Protein Kinase Inhibitors/therapeutic use ; Receptor, Epidermal Growth Factor/*antagonists & inhibitors/genetics ; Transglutaminases/*biosynthesis ; Treatment Outcome

Recently, rearranged during transfection (RET) fusions have been identified in approximately 1% of non-small cell lung cancer (NSCLC). To know the prevalence of RET fusion genes in Korean NSCLCs, we examined the RET fusion genes in 156 surgically resected NSCLCs using a reverse transcriptase polymerase chain reaction. Two KIF5B-RET fusions and one CCDC6-RET fusion were identified. All three patients were females and never smokers with adenocarcinomas. RET fusion genes were mutually exclusive from EGFR, KRAS mutations and EML4-ALK fusion. RET fusion genes occur 1.9% (3 of 156) of surgically treated NSCLC patients in Koreans.
Asian Continental Ancestry Group/*genetics ; Carcinoma, Non-Small-Cell Lung/epidemiology/*genetics/surgery ; Cytoskeletal Proteins/genetics ; Female ; Humans ; Kinesin/genetics ; Lung Neoplasms/epidemiology/*genetics/surgery ; Middle Aged ; Oncogene Proteins, Fusion/*genetics ; Proto-Oncogene Proteins c-ret/*genetics ; Republic of Korea/epidemiology ; Sequence Analysis, DNA

OBJECTIVETo investigate the standard protocol for anaplastic lymphoma kinase (ALK) fusion gene assessment by fluorescent in situ hybridization (FISH) in non-small cell lung cancer (NSCLC).

METHODSTissue specimens of NSCLC cases were retrospectively collected from Jan. 2011 to July 2012. ALK fusion gene was examined by FISH using break-apart ALK gene probes (Vysis company). The identification of ALK fusion gene was determined by fluorescent signals under a fluorescence microscope.

RESULTSOne hundred and forty-six eligible NSCLC tumor specimens were tested for ALK fusion gene by FISH. The specimens included 110 cases (75.4%) of surgically-removed tissues, 11 cases (7.5%) of biopsy, 19 cases (13.0%) of lymph node and 6 cases (4.1%) of other metastatic tissues. The positivity of ALK fusion gene was 8.9% (13/146).

CONCLUSIONSThe assessment of ALK fusing gene by FISH using standard protocol for formalin-fixed, paraffin-embedded (FFPE) tissue is feasible. The protocol can used to test in surgically-removed tissues, biopsies, metastatic lymph nodes and other metastastic specimens.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; surgery ; Female ; Gene Fusion ; Humans ; In Situ Hybridization, Fluorescence ; Lung Neoplasms ; genetics ; metabolism ; surgery ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Paraffin Embedding ; Receptor Protein-Tyrosine Kinases ; genetics ; metabolism ; Retrospective Studies ; Young Adult

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

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 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