In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC.
Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; genetics ; pathology ; Humans ; Lung Neoplasms ; diagnosis ; drug therapy ; genetics ; pathology ; Mutation ; Prognosis

Lung cancer is one of the most important malignant tumors in the world. The morbidity and mortality rank the first in all kinds of cancer. Long non-coding RNA (lncRNA) is at least 200 nt long and has no protein coding capacity. It plays an important role in the epigenetic regulation, cell cycle regulation, the regulation of cell differentiation, and many other life activities. The studies indicate that dysregulation of lncRNAs in non-small cell lung cancer (NSCLC) tissue and blood circulation is associated with the occurrence and development of cancer. The lncRNAs play an significant role in proliferation, differentiation, migration and apoptosis of the tumor cells. Explore the potential mechanism between lncRNAs and NSCLC is beneficial for the early diagnosis, target therpy and improve prognosis. Therefore, the study aims to demonstrate the latest studies on the lncRNAs related to occurence, diagnosis, therpy and prognosis of NSCLC. It can help to deeply understanding of lncRNA, and provide new ideas for the prevention of NSCLC.
Carcinogenesis ; genetics ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; genetics ; pathology ; Humans ; Molecular Targeted Therapy ; RNA, Long Noncoding ; genetics

Pulmonary enteric adenocarcinoma (PEAC), as a rare histologic subtype of primary lung adenocarcinoma, is defined as an adenocarcinoma in which the enteric component exceeds 50%. It is named after its shared morphological and immunohistochemical features with colorectal cancer. While with such similarity, the differential diagnosis of PEAC and lung metastatic colorectal cancer is a great challenge in the clinic. PEAC may originate from the intestinal metaplasia of respiratory basal cells stimulated by risk factors such as smoking. Current studies have found that KRAS is a relatively high-frequency mutation gene, and other driver gene mutations are rare. In terms of immunohistochemistry, in pulmonary enteric adenocarcinoma, the positive rate was 88.2% (149/169) for CK7, 78.1% (132/169) for CDX2, 48.2% (82/170) for CK20 and 38.8% (66/170) for TTF1. As for clinical features, the average age of onset for pulmonary enteric adenocarcinoma was 62 years, male patients accounted for 56.5% (35/62), smokers accounted for 78.8% (41/52), and 41.4% (24/58) of the primary lesion was located in the upper lobe of the right lung. In terms of treatment, conventional non-small cell lung cancer (NSCLC) regimens rather than colorectal cancer regimens are now recommended. There is still an urgent need for more basic and clinical research, in-depth exploration of its molecular feature and pathogenesis from the level of omics and other aspects, to help diagnosis and differential diagnosis, and find the optimal chemotherapy regimen, possibly effective targeted therapy and even immunotherapy.
Adenocarcinoma/pathology* ; Adenocarcinoma of Lung/pathology* ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung/diagnosis* ; Colonic Neoplasms/pathology* ; Diagnosis, Differential ; Humans ; Lung Neoplasms/genetics* ; Male ; Middle Aged

Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; pathology ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms ; diagnosis ; genetics ; pathology ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUND: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has emerged as an innovative technique for diagnosis and staging of lung cancer. But whether the procedure can provide enough tissue for the detection of gene mutations is still to be defined. Here we evaluated the efficacy of lung cancer diagnosis and gene analysis using samples obtain via EBUS-TBNA. METHODS: Patients with suspected lung cancer and mediastinal lesions were referred for EBUS-TBNA. Diagnosis and sub-classifications were made by pathologists. Samples with non-squamous non small cell lung cancer sub type were tested for the EGFR and/or ALK mutations. RESULTS: A total of 377 patients were included in this study. The median needle passes were 2.07. Lung cancer was diagnosed in 213 patients. The diagnosis accuracy for malignancy was 92%. Epidermal growth factor receptor (EGFR) mutations, anaplasticlymphoma kinase (ALK) fusion genes and double genes analysis were successfully preformed in 84 (90%), 105 (95%) and 79 (90%) patients. The number of needle passes and the diameters of lymph node were not associated with the efficacy of gene testing in univariate analysis. However, samples of adenocarcinoma sub type showed a tendency associated with higher genotyping efficacy. CONCLUSIONS Tissue samples obtained through EBUS-TBNA are sufficient for pathological diagnosis and genetic analysis of lung cancer. The pathology type of sample affected genotyping efficacy.
Adult ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; pathology ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Feasibility Studies ; Female ; Genotyping Techniques ; Humans ; Lung Neoplasms ; diagnosis ; genetics ; pathology ; Male

Hypoxia-inducible factor-1 alpha (HIF-1α) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer (NSCLC) patients had higher HIF-1α expression than small cell lung cancer (SCLC) patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.
Adenocarcinoma ; diagnosis ; genetics ; mortality ; pathology ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; mortality ; pathology ; Carcinoma, Squamous Cell ; diagnosis ; genetics ; mortality ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Lung Neoplasms ; diagnosis ; genetics ; mortality ; pathology ; Lymphatic Metastasis ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Prognosis ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Survival Analysis ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo investigate gene diagnosis of occult micrometastasis in the mediastinal lymph node in patients with non-small cell lung carcinoma (NSCLC) and to evaluate its prognostic significance.

METHODSWith mRNA expression of mucoid1 (MUC1) gene examined by RT-PCR, 168 mediastinal lymph nodes taken from 37 pN(0) (negative lymph nodes) NSCLC patients (stage Ia approximately IIb) made up the experiment group. Thrity negative lymph nodes from 14 benign lesions and 30 positive lymph nodes from 15 NSCLC patients served as control. The survival difference between MUC1 mRNA-negative and MUC1 mRNA-positive groups was compared by the chi(2) test.

RESULTSUC1 mRNA was not identified in the negative-control group (specificity = 100%), but it was identified in 26 of 30 positive-control samples (sensitivity = 86.7%). MUC1 mRNA was identified in 16 (9.5%) of the experiment group from 12 patients whose TNM stage was up-regulated to stage IIIa. The 3-year survival rate (58.3%) of MUC1 mRNA positive group patients with occult micrometastasis in mediastinal lymph node was lower than the 88.0% of MUC1 mRNA negative group (P < 0.05).

CONCLUSIONOccult micrometastasis in the mediastinal lymph node in NSCLC patients can be diagnosed by MUC1 mRNA expression through RT-PCR. Poor prognosis in some pN(0) NSCLC patients may be associated with nodal occult micrometastasis.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; secondary ; Female ; Genetic Markers ; genetics ; Humans ; Lung Neoplasms ; diagnosis ; pathology ; Lymphatic Metastasis ; diagnosis ; Male ; Middle Aged ; Mucin-1 ; analysis ; genetics ; Prognosis ; RNA, Messenger ; analysis

Due to the advanced diagnostic technique and better understanding for multiple primary lung cancers (MPLC), the increasing incidence of MPLC has been reported. Very often, MPLC are misdiagnosed as metastasis because of lacking efficient molecular biomarkers for prediction and diagnosis. Studies on the molecular mechanism for tumorgenesis and progression of MPLC may therefore facilitate the discovery of biomarkers for disease diagnosis and prognosis, so that an individual and rational treatment can be achieved. We tried to further our understanding and improve the diagnostic skill for MPLC by reviewing the current status and the latest advancement of molecular markers related to MPLC.
Adenocarcinoma ; pathology ; Biomarkers, Tumor ; analysis ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; radiotherapy ; Carcinoma, Small Cell ; pathology ; Carcinoma, Squamous Cell ; pathology ; Chromosome Deletion ; DNA Damage ; Genes, Tumor Suppressor ; Humans ; Incidence ; Lung Neoplasms ; diagnosis ; epidemiology ; etiology ; genetics ; Neoplasms, Multiple Primary ; diagnosis ; epidemiology ; etiology ; genetics ; Smoking ; adverse effects

No abstract available.
Antineoplastic Agents/therapeutic use ; Ascitic Fluid/*cytology ; Carcinoma, Non-Small-Cell Lung/*diagnosis/drug therapy/pathology ; Humans ; Lung Neoplasms/*diagnosis/drug therapy/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Quinazolines/therapeutic use ; Receptor, Epidermal Growth Factor/genetics ; Small Cell Lung Carcinoma/*diagnosis/pathology ; Tomography, X-Ray Computed

Detection of genetic alterations could provide a tool as an adjuvant for the diagnosis of non-small cell lung cancer (NSCLC) and to define patients at risk for early relapse. In this study, a multi-target fluorescence in situ hybridization (FISH) assay was conducted to investigate the correlation between the alterations of chromosomes, including 5p15.2, 6p11.1-q11, 7p12, and 8q24.12-q24.13 (LaVysion Test), and clinicopathological variables, and to clarify the potential of the multi-target FISH assay in 37 NSCLC. The most notable finding was the higher frequency of a gain in chromosome 5p15.2 in early-stage (I+IIa) lung cancers. The frequency of the gain was 81.3% (16/22) in stage I tumors. The frequencies of gains in 6p11.1-q11 and 8q24.12-q24.13 were 61.5% (8/13) and 84.6% (11/13) in stage IIIa cancers, as compared with lower frequencies in stage I tumors at 25.0% and 31.3%, respectively. There was also a significant difference in the histological type. Our results suggest that a gain in 6p11.1-q11 and 8q24.12-q24.13 plays an important role in tumor progression and is associated with histological differentiation. On the other hand, gene amplification in the 5p region was one of the most consistent alterations in early-stage lung cancer, and thus a series of genes in the critical 5p15.2 region might potentially associated with the development of lung cancer.
Aged ; Carcinoma, Non-Small-Cell Lung/diagnosis/*genetics/pathology ; *Chromosome Aberrations ; Chromosomes, Human, Pair 5/genetics ; Chromosomes, Human, Pair 6/genetics ; Chromosomes, Human, Pair 8/genetics ; Female ; Gene Amplification ; Humans ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/diagnosis/*genetics/pathology ; Male ; Middle Aged ; Neoplasm Staging ; Tumor Markers, Biological/genetics