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

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

MicroRNAs (miRNAs) a class of non-coding RNAs about 22 nt in size that are found in a wide range of organisms from plants, viruses to humans. MicroRNA has a wide range of biological functions. It can recruit related RNA enzymes and lead to mRNA degradation after binding to mRNA specificity, thus blocking the expression of protein encoding genes and then affecting their biological functions. In recent years, microRNA has been found to be closely related to the biological behaviors, such as the occurrence, development, invasion and metastasis of multiple human malignant carcinomas, and play a regulatory role in the above biological phenotypes. Lung cancer is the highest incidence of malignancy. The exact molecular mechanism of its occurrence and development has not been fully elucidated. Previous studies have shown that microRNA plays an important role in lung tumor suppressor gene inactivation, oncogene activation and epigenetics. At the same time, there are also reports that there is a significant difference in the expression of microRNA in patients with lung cancer and benign lung diseases. This differential expression provides a basis for the feasibility of microRNA as a diagnostic and pre biological marker for lung cancer.
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Humans ; Lung Neoplasms ; diagnosis ; genetics ; pathology ; MicroRNAs ; genetics ; Neoplasm Invasiveness ; Neoplasm Metastasis

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

Pain perception is influenced by multiple factors. The single nucleotide polymorphisms (SNPs) of some genes were found associated with pain perception. This study aimed to examine the association of the genotypes of ABCB1 C3435T, OPRM1 A118G and COMT V108/158M (valine 108/158 methionine) with pain perception in cancer patients. We genotyped 146 cancer pain patients and 139 cancer patients without pain for ABCB1 C3435T (rs1045642), OPRM1 A118G (rs1799971) and COMT V108/158M (rs4680) by the fluorescent dye-terminator cycle sequencing method, and compared the genotype distribution between groups with different pain intensities by chi-square test and pain scores between groups with different genotypes by non-parametric test. The results showed that in these cancer patients, the frequency of variant T allele of ABCB1 C3435T was 40.5%; that of G allele of OPRM1 A118G was 38.5% and that of A allele of COMT V108/158M was 23.3%. No significant difference in the genotype distribution of ABCB1 C3435T (rs1045642) and OPRM1 A118G (rs1799971) was observed between cancer pain group and control group (P=0.364 and 0.578); however, significant difference occurred in the genotype distribution of COMT V108/158M (rs4680) between the two groups (P=0.001). And the difference could not be explained by any other confounding factors. Moreover, we found that the genotypes of COMT V108/158M and ABCB1 C3435T were associated with the intensities of pain in cancer patients. In conclusion, our results indicate that the SNPs of COMT V108/158M and ABCB1 C3435T significantly influence the pain perception in Chinese cancer patients.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Breast Neoplasms ; complications ; diagnosis ; genetics ; pathology ; Catechol O-Methyltransferase ; genetics ; Female ; Gastrointestinal Neoplasms ; complications ; diagnosis ; genetics ; pathology ; Gene Expression ; Gene Frequency ; Genital Neoplasms, Female ; complications ; diagnosis ; genetics ; pathology ; Genital Neoplasms, Male ; complications ; diagnosis ; genetics ; pathology ; Genotype ; Humans ; Lung Neoplasms ; complications ; diagnosis ; genetics ; pathology ; Male ; Middle Aged ; Pain ; complications ; diagnosis ; genetics ; pathology ; Pain Measurement ; Pain Perception ; Polymorphism, Single Nucleotide ; Receptors, Opioid, mu ; genetics

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

Extraskeletal Ewing's sarcoma (EES) is a branch of neuroectodermal tumor (PNET), which is very rare soft tissue sarcoma. We report a case of EES/PNET arising is the lung of a 67-yr-old man. Computed tomography, bone scintigraphy, and positron emission tomography confirmed the mass to have a primary pulmonary origin. The mass showed positive reactivity in the Periodic Acid Schiff (PAS) stain and MIC-2 immunoreactivity in immunohistochemical stain. Fluorescence in situ hybridization (FISH) was performed, which revealed an EWSR1 (Ewing sarcoma breakpoint region 1) 22q12 rearrangement. The diagnosis was confirmed both pathologically and genetically. The mass lesion was resected, and the patient is currently undergoing chemotherapy.
Aged ; Calmodulin-Binding Proteins/genetics ; Chromosome Breakage ; Chromosomes, Human, Pair 22/genetics ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*diagnosis/genetics/metabolism/pathology ; Male ; Neuroectodermal Tumors, Primitive, ; RNA-Binding Proteins/genetics ; Sarcoma, Ewing's/*diagnosis/genetics/metabolism/pathology

Adenocarcinoma ; pathology ; Carcinoma, Small Cell ; pathology ; Carcinoma, Squamous Cell ; pathology ; Diagnosis, Differential ; Humans ; Lung Neoplasms ; classification ; genetics ; pathology ; World Health Organization

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