1.Research Advances of Pan-negative Type of Non-small Cell Lung Cancer.
Li SUN ; Zhicheng XIONG ; Chengbo HAN
Chinese Journal of Lung Cancer 2018;21(2):129-138
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
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diagnosis
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drug therapy
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genetics
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pathology
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Humans
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Lung Neoplasms
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diagnosis
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drug therapy
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genetics
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pathology
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Mutation
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Prognosis
2.Progress of Long Non-coding RNA in Non-small Cell Lung Cancer.
Yachen ZHANG ; Di LIANG ; Jing JIN ; Congmin LIU ; Yutong HE
Chinese Journal of Lung Cancer 2018;21(1):43-49
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
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genetics
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Carcinoma, Non-Small-Cell Lung
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diagnosis
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drug therapy
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genetics
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pathology
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Humans
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Molecular Targeted Therapy
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RNA, Long Noncoding
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genetics
3.Advances in Double Mutations of EGFR and ALK Gene in Non-small Cell Lung Cancer.
Chinese Journal of Lung Cancer 2018;21(9):686-691
Molecular target therapy is one of the most popular field of non-small cell lung cancer (NSCLC) treatmnet. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearragement are the most important two oncogenic drivers in NSCLC, early studies suggested that EGFR mutations and ALK rearrangements are mutually exclusive, but isolated cases or small sample research with concomitant EGFR and ALK alterations have been constantly reported. The co-occurrence of EGFR mutations and anaplastic lymphoma kinase (ALK) rearrangements constitutes a rare molecular, the frequency of EGFR/ALK co-alterations was about 1%, however, little has been known about clinicopathologic feature and treatment. This review summarized published case report, EGFR and ALK alterations are common in female, Asian origin, never smoker, IV stage, and denocarcinomas. First-line treatment can choose EGFR or ALK tyrosine kinase inhibitors (TKIs). However, studies about the origin and resistance mechanism in EGFR/ALK co-alterations are little, require more experimental and clinical research.
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Anaplastic Lymphoma Kinase
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Carcinoma, Non-Small-Cell Lung
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diagnosis
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enzymology
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genetics
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ErbB Receptors
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genetics
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Humans
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Lung Neoplasms
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diagnosis
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enzymology
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genetics
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Mutation
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Prognosis
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Receptor Protein-Tyrosine Kinases
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genetics
6.Progress in pulmonary enteric adenocarcinoma.
Ying ZUO ; Hua BAI ; Jian Ming YING ; Jie WANG
Chinese Journal of Oncology 2022;44(4):321-325
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*
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Adenocarcinoma of Lung/pathology*
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Biomarkers, Tumor
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Carcinoma, Non-Small-Cell Lung/diagnosis*
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Colonic Neoplasms/pathology*
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Diagnosis, Differential
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Humans
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Lung Neoplasms/genetics*
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Male
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Middle Aged
7.Endobronchial Ultrasound Guided Transbronchial Needle Aspiration for The Diagnosis and Genotyping of Lung Cancer.
Minjiang CHEN ; Chi SHAO ; Yan XU ; Xuefeng SUN ; Jing ZHAO ; Yong CHEN ; Yuanyuan ZHAO ; Wei ZHONG ; Mengzhao WANG
Chinese Journal of Lung Cancer 2018;21(9):670-676
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
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Carcinoma, Non-Small-Cell Lung
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diagnosis
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genetics
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pathology
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Endoscopic Ultrasound-Guided Fine Needle Aspiration
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Feasibility Studies
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Female
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Genotyping Techniques
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Humans
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Lung Neoplasms
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diagnosis
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genetics
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pathology
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Male
8.Significance of combined detection of plasma RASSF1A and p16 gene methylation in diagnosis of non-small cell lung cancers.
Gui-zhi LIU ; Yi-ming WU ; Ji-yao YANG
Chinese Journal of Oncology 2007;29(8):613-614
Adenocarcinoma
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diagnosis
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genetics
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Carcinoma, Non-Small-Cell Lung
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diagnosis
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genetics
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Carcinoma, Squamous Cell
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diagnosis
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genetics
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Cyclin-Dependent Kinase Inhibitor p16
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blood
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metabolism
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DNA Methylation
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Genes, p16
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Humans
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Lung Neoplasms
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diagnosis
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genetics
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Tumor Suppressor Proteins
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blood
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metabolism
9.Construction of a repeat-free dual color fluorescent in situ hybridization probe for ROS1 gene in non-small cell lung cancer diagnosis.
Hongxia CHENG ; Lun YE ; Liquan XUE
Chinese Journal of Pathology 2014;43(6):399-402
OBJECTIVETo establish a repeat-free ROS1 gene fluorescence in situ hybridization (FISH) probe, and to compare its efficacy with those of commercial FISH probes in non-small cell lung cancer.
METHODSThe probe was constructed by combining human Cot-1 DNA genome into double-stranded sequence, and then digested by duples specific nuclease to establish a repeat-free sequence. The final repeat-free ROS1 FISH probe was labeled by red and green fluoresceins.
RESULTSCompared with the commercialized probe, repeat-free FISH probe exhibited excellent efficiency and low signal to noise ratio (SNR) in samples. There was statistical significance in the difference between the hybridization rate of these two probes (P < 0.05) , but there was no difference between the accuracy rate (P > 0.05).
CONCLUSIONThe repeat-free ROS1 FISH probe significantly improves the probe hybridization efficiency and SNR in non-small cell lung cancer (NSCLC), resulting in an increased accuracy of detection.
Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; Fluorescent Dyes ; Humans ; In Situ Hybridization, Fluorescence ; Protein-Tyrosine Kinases ; genetics ; Proto-Oncogene Proteins ; genetics
10.A standard protocol for detection of EGFR mutations in cytologic specimens.
Zheng WANG ; Xiaonan WU ; Yuankai SHI ; Xiaohong HAN ; Gang CHENG ; Lin LI ; Li ZHANG ; Yuhui ZHANG ; Xinlin MU ; Guangqing ZHU ; Zaiwen FAN ; Li YANG ; Jing DI ; Xinrui JIA ; Dongge LIU
Chinese Journal of Oncology 2014;36(7):516-521
OBJECTIVEThe aim of this study was to establish a standard protocol for detection of EGFR mutations in cytologic specimens.
METHODS287 cytologic samples were collected from the patients who were suspected of having lung cancer at six hospitals in Beijing. A detection protocol for EGFR mutations was designed. Two comparative experiments were carried out for the coincidence in EGFR mutation rates between direct sequencing (Seq) and amplification refractory mutation system (ARMS) methods, and between 40 matched cytologic samples with formaldehyde-fixed paraffin embedded (FFPE) cytologic blocks and cytospin slides.
RESULTSTumor cells were found in 236 out of 287 cases (82.2%, 236/287) . Among them, there were 31 cases (13.1%, 31/236) of low tumor cell content samples and 205 cases (86.9%, 205/236) of high tumor cell content samples. 180 cases in the high tumor cell content samples (87.8%, 180/205) were diagnosed to be consistent with NSCLC. 25 out of 194 cases were ruled out or indefinite to be diagnosed as NSCLC by immunohistochemistry. By direct sequencing, the mutation rate of EGFR was 27.8% (50/180) in NSCLC samples and 28.2% (50/177) in adenocarcinoma samples (high tumor content samples) . By ARMS, the mutation rate of EGFR was 45.6% (82/180) in NSCLC samples and 46.3% (82/177) in adenocarcinoma samples (high tumor content samples). The EGFR mutation rate in low tumor content samples was 38.7% (12/31) , there was no significant difference in EGFR mutation rates between the groups of low tumor cell content samples and high tumor cell content samples (P = 0.12). The concordance rate of EGFR mutation rates was 100% between scraping tumor cells from slides samples and from FFEP blocks in the 40 matched samples. Forty-eight out of 180 definitive NSCLC patients received Gefitinib therapy. The FPS was 12 months in the gefitinib-treated ARMS⁺ group and 2 months in the ARMS⁻ group (P < 0.001), and the OS was 19 months in the gefitinib-treated ARMS⁺ group and 7 months in the ARMS⁻ group (P = 0.003), but no significant differences were found in the efficacy (PFS and OS) of Gefitinib between Seq⁺ and Seq⁻ groups (P = 0.227, P = 0.510, respectively), and Seq⁺/ARMS⁺ and Seq⁻/ARMS⁺ groups (P = 0.354, P = 0.334, respectively).
CONCLUSIONSThe detection protocol for EGFR mutations in cytological specimens introduced in this study is tested to be reliable and feasible. Pathological evaluation and immunohistochemistry are important in the detection procedure of EGFR mutations in cytologic specimens. High sensitivity methods should be selected for detection of EGFR mutations in cytologic samples.
Adenocarcinoma ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; Humans ; Lung Neoplasms ; diagnosis ; epidemiology ; metabolism ; Mutation ; Mutation Rate ; Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; genetics ; metabolism