Breast Neoplasms/genetics* ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; MicroRNAs/genetics*

Pulmonary carcinoids are infrequent neoplasms of the lung that normally display a less aggressive biological behavior compared to small cell and non-small cell lung cancers. Approximately 15-25% of carcinoids, in particular atypical carcinoids, show lymph node metastasis and have a worse prognosis than their non-metastasized counterparts. To date, there is no morphological or molecular marker that may help to differentiate between carcinoids that metastasize and carcinoids of identical differentiation that show only local tumor growth. In this study, we analyzed 7 metastasized and 10 non-metastasized pulmonary carcinoids for chromosomal and microsatellite instability in order to determine whether microsatellite instability or chromosomal imbalances are associated with metastasis. Due to the rare occurrence of metastasized carcinoids we compared our results of chromosomal instability with the hitherto published comparative genomic hybridization (CGH) profiles of pulmonary carcinoids, for which information about the absence or presence of metastasis was available. While microsatellite instability was not detected we found chromosomal instability as a common event in pulmonary carcinoids with an increase of frequency and extent of chromosomal alterations in atypical and metastasized carcinoids. These findings are in accordance with the collected and herein compiled data of previous studies and indicate increasing numbers of chromosomal imbalances to play a role in the sequential process of tumor development and metastasis.
Carcinoid Tumor/*genetics/pathology/*secondary ; Chromosomal Instability/*genetics ; Comparative Genomic Hybridization ; Humans ; Lung Neoplasms/*genetics/pathology ; Lymphatic Metastasis ; Prognosis

Pulmonary carcinoids are infrequent neoplasms of the lung that normally display a less aggressive biological behavior compared to small cell and non-small cell lung cancers. Approximately 15-25% of carcinoids, in particular atypical carcinoids, show lymph node metastasis and have a worse prognosis than their non-metastasized counterparts. To date, there is no morphological or molecular marker that may help to differentiate between carcinoids that metastasize and carcinoids of identical differentiation that show only local tumor growth. In this study, we analyzed 7 metastasized and 10 non-metastasized pulmonary carcinoids for chromosomal and microsatellite instability in order to determine whether microsatellite instability or chromosomal imbalances are associated with metastasis. Due to the rare occurrence of metastasized carcinoids we compared our results of chromosomal instability with the hitherto published comparative genomic hybridization (CGH) profiles of pulmonary carcinoids, for which information about the absence or presence of metastasis was available. While microsatellite instability was not detected we found chromosomal instability as a common event in pulmonary carcinoids with an increase of frequency and extent of chromosomal alterations in atypical and metastasized carcinoids. These findings are in accordance with the collected and herein compiled data of previous studies and indicate increasing numbers of chromosomal imbalances to play a role in the sequential process of tumor development and metastasis.
Carcinoid Tumor/*genetics/pathology/*secondary ; Chromosomal Instability/*genetics ; Comparative Genomic Hybridization ; Humans ; Lung Neoplasms/*genetics/pathology ; Lymphatic Metastasis ; Prognosis

OBJECTIVETo investigate the correlation of microRNA-155 (miR-155) expression with clinicopathological features of patients with papillary thyroid carcinoma (PTC) and explore the value of miR-155 in prognostic assessment of PTC.

METHODSWe collected 86 pairs of fresh PTC and adjacent tissues to examine the expression of miR-155 using fluorescent quantitative PCR. miR-155 expressions in the tissues were analyzed in relation to the clinicopathological features of the patients.

RESULTSCompared with the paired adjacent tissues, 69.8% (60/86) of the PTC tissues showed up-regulated miR-155 expression by 2.63∓2.73 folds. Up-regulated miR-155 expressions were associated with a larger tumor size (1.66∓0.96 vs 1.19∓0.52 cm, P=0.021), a higher likeliness of extrathyroid invasion (56.7% vs 23.1%, P=0.004), a higher rate of lymph node metastasis (70% vs 46.2%, P=0.036), a more advanced TNM stage, and a higher rate of III-IV stage of the tumor (20% vs 0%, P=0.014). The expression level of miR-155 in PTC tissues was positively correlated with lymph node metastasis (r=0.531, P=0.001).

CONCLUSIONPTC patients with miR-155 over-expression tend to have a greater tumor size, a greater likeliness of extrathyroid involvement, a higher rate of cervical lymph node metastasis and a more advanced TNM stage. The high expression of miR-155 in the tumor may indicate a poor prognosis of PTC patients.

Carcinoma, Papillary ; genetics ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; MicroRNAs ; genetics ; Neck ; Prognosis ; Thyroid Neoplasms ; genetics ; Up-Regulation

OBJECTIVE: To analyze the correlation of methylation status of dachshund homolog 1 (DACH1) gene in tumor tissues with clinicopathological characteristics and prognosis of patients of esophageal cancer. METHODS: Tumor tissue, paracancerous tissue and normal esophageal mucosal specimens of 104 patients with esophageal cancer were collected. Methylation-specific PCR was used to determine the methylation status of the DACH1 gene. Univariate analysis and multivariate Logistic regression model were used to analyze the correlation between DACH1 methylation status and clinical pathological characteristics of the patients. Kaplan-Meier survival curve was used to analyze the relationship between DACH1 methylation status and prognostic survival of patients. RESULTS: The methylation rate of the DACH1 gene in esophageal cancer tumor tissue was 30.77% (32/104), which was higher than those in adjacent tissues (1.92%) and normal esophageal mucosa (0%) (P< 0.05). The methylation status of the DACH1gene in tumor tissues of patients did not correlate with the patient's age, gender, and pathological type (P> 0.05) but tumor differentiation, TNM staging, and lymph node metastasis(P< 0.05). The degree of tumor differentiation, TNM stage, and lymph node metastasis of patients are independent risk factors for the methylation status of the DACH1 gene. By March 2020, 89 of the 104 patients had died. Among them, the median survival foresophageal cancer patients with DACH1 gene methylation was 22 months, which was lower than 34 months of those without DACH1 methylation (P< 0.05). CONCLUSION Methylation of the DACH1 gene may be involved in the occurrence and progress of esophageal cancer. The degree of tumor differentiation, TNM stage, and lymph node metastasis of patients are independent risk factors for the methylation status of the DACH1 gene. Patients with esophageal cancer but unmethylated DACH1 gene have a longer prognostic survival.
Esophageal Neoplasms/pathology* ; Eye Proteins/genetics* ; Humans ; Lymphatic Metastasis ; Methylation ; Neoplasm Staging ; Prognosis ; Transcription Factors

Metastasis is the leading cause of mortality for cancer patients, and lymphatic metastasis is one of the main ways of tumor metastasis. The role of CCL21 and its receptor CCR7 in lymphatic metastasis has been increasingly concerned in recent years. CCR7 is mainly expressed by both dendritic cells and T cells for immune responses. CCL21, the chemokine ligand for CCR7, secreted from lymphatic endothelial cells binds CCR7 and recruits immune cells toward lymphatic vessels and lymphatic nodes. CCR7 expressed tumor cells can also metastasize to lymphatic system by the similar way as immune cells. Targeting CCL21/CCR7 axis to inhibit lymphatic metastasis but remain potent anti-tumor immune response has increasingly become a spot light of tumor immunotherapy. In this review, we summarize the role of CCL21/CCR7 axis in lymphatic metastasis, as well as preclinical trials and clinical trials in targeting CCL21/CCR7 axis for tumor metastasis therapy, hoping to accelerate the progress on tumor metastasis therapy by targeting CCL21/CCR7 axis.
Cell Line, Tumor ; Chemokine CCL21 ; Endothelial Cells ; Humans ; Lymphatic Metastasis ; Neoplasms/therapy* ; Receptors, CCR7/genetics*

Objective: To analyze poly-guanine (poly-G) genotypes and construct the phylogenetic tree of colorectal cancer (CRC) and provide an efficient and convenient method for the study of intra-tumor heterogeneity and tumor metastasis pathway. Methods: The clinicopathological information of patients with primary colorectal cancer resection with regional lymph node metastases were retrospectively collected in the Department of General Surgery, General Hospital of Tianjin Medical University from January 2017 to December 2017. The paraffin sections of the paired tumor samples were performed consecutively, and multi-region microdissection was performed after histogene staining. The phenol-chloroform extraction and ethanol precipitation scheme was used to obtain DNA, and Poly-G multiplex PCR amplification and capillary electrophoresis detection were performed. The correlation between Poly-G mutation frequency and clinicopathological parameters was analyzed. Based on the difference of Poly-G genotypes between paired samples, the distance matrix was calculated, and the phylogenetic tree was constructed to clarify the tumor metastasis pathway. Results: A total of 237 paired samples were collected from 20 patients including 134 primary lesions, 66 lymph node metastases, 37 normal tissues, and Poly-G mutation was detected in 20 patients (100%). The mutation frequency of Poly-G in low and undifferentiated patients was (74.10±23.11)%, higher than that in high and medium differentiated patients [(31.36±12.04)%, P<0.001]. In microsatellite instability patients, the mutation frequency of Poly-G was (68.19±24.80)%, which was higher than that in microsatellite stable patients [(32.40±14.90)%, P=0.003]. The Poly-G mutation frequency was not correlated with age, gender, and pathological staging (all P>0.05). Based on Poly-G genotype difference of the paired samples, the phylogenetic trees of 20 patients were constructed, showing the evolution process of the tumor, especially the subclonal origins of lymph node metastasis. Conclusion: Poly-G mutations accumulate in the occurrence and development of CRC, and can be used as genetic markers to generate reliable maps of intratumor heterogeneity in large numbers of patients with minimal time and cost expenditure.
Humans ; Lymphatic Metastasis ; Retrospective Studies ; Poly G ; Phylogeny ; Mutation ; Colorectal Neoplasms/pathology* ; Biomarkers, Tumor/genetics*

Lung cancer ranks the first cancer-related morbidity and mortality in China. Tumor metastasis always predicts the poor prognosis for patients. Moreover, lymphatic metastasis is one of the most significant predictors of poor prognosis in patients with non-small cell lung cancer (NSCLC) and lymphangiogenesis represents the bridge that functionally facilitates tumor lymphatic metastasis. In this review, we first discussed the molecular mechanisms of tumor-associated lymphangiogenesis and the interaction between tumor microenvironment and lymphatic endothelial cells, then, summarized the role of non-coding RNA in regulating tumor-associated lymphangiogenesis in recent frontier studies, with the aim to provide some novel insights on NSCLC-related lymphangiogenesis research, diagnosis and treatment.
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Carcinoma, Non-Small-Cell Lung/genetics* ; Disease Progression ; Endothelial Cells ; Humans ; Lung Neoplasms/genetics* ; Lymphangiogenesis ; Lymphatic Metastasis ; Lymphatic Vessels ; Tumor Microenvironment ; Vascular Endothelial Growth Factor C

OBJECTIVETo identify the differentially expressed genes related to lymphatic metastasis of lung squamous cell carcinoma.

METHODSSpecimens of primary lung squamous cancer tissues and regional lymph nodes were obtained from 10 patients undergoing complete surgical resection of the tumor. The samples were classified into 3 groups, namely the primary tumor with lymphatic metastasis (TxN+, n=5), primary tumor without lymphatic metastasis (TxN-, n=5) and matched tumor cells from the metastatic lymph nodes (N+, n=5). The total RNA extracted from the laser microdissected primary tumor or metastatic nodes was labeled and hybridized with the microarray containing 6 000 known human genes or ESTs. Data analysis was performed using GeneSpring(TM) 6.2 software. Immunohistochemical staining was used to detect the expression of CCL20 in the specimens.

RESULTSA total of 37 genes showed differential expressions between TxN+ and TxN- tissues, among which 8 genes were upregulated and 29 were downregulated in TxN+ group. No genes, however, showed distinct differential expressions between N+ and TxN+ tissues. The expression of CCL20 was significantly higher in TxN- than in TxN+ tissues (P<0.05).

CONCLUSIONThe acquisition of the metastatic phenotype may occur early in the development of lung squamous cancer. The gene expression signature of lung squamous cell carcinoma is valuable to elucidate the molecular mechanisms regarding lymphatic metastasis of the malignancy, and may provide important clues for exploring novel therapeutic targets.

Carcinoma, Squamous Cell ; genetics ; pathology ; DNA Fingerprinting ; Gene Expression ; Gene Expression Profiling ; Humans ; Lung Neoplasms ; genetics ; pathology ; Lymphatic Metastasis

OBJECTIVETo investigate the clinical features of familial papillary thyroid carcinoma (FPTC) and the criteria for its diagnosis and surgical treatment.

METHODSOne hundred and forty-five patients with PTC were investigated randomly between January 1999 and November 2001, and 17 of them were from 7 families. Of the 17 patients, 14 were operated on at this hospital, and 3 were operated elsewhere. The specimens from the 17 patients were confirmed pathologically. They accounted for 9.3% (14/145) of all PTC patients.

RESULTSThe patients were aged from 30 to 74 years (mean 45 years). The diameter of original focuses ranged from 0.8 to 2.8 cm (mean diameter 1.7 cm). Of the 17 patients with PTC, 8 (47.5%) had bilateral carcinoma. In 3 families, 3 patients suffered from PTC (42.8%). In 4 families, other members suffered from benign thyroid tumor or non-tumorous thyroid disease. Among the 17 patients, 10 had nodular goiters. Thyroidectomy, unilateral thyroidectomy plus isthmusectomy, and combined radical operation were performed in 8, 9, 14 patients, respectively. Early metastatic spread to local regional lymph nodes was noted in 14 patients (82.3% or 14/17).

CONCLUSIONSIn this study, a FPTC rate of 10% was found. Almost 50% of FPTC patients had bilateral carcinoma. The frequency of metastatic spread to local-regional lymph nodes was high. Follow-up survey of family members should be performed in a long period of time.

Adult ; Aged ; Carcinoma, Papillary ; genetics ; pathology ; surgery ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Thyroid Neoplasms ; genetics ; pathology ; surgery ; Thyroidectomy