Level II lateral neck dissection for papillary thyroid carcinoma: A retrospective cohort study.

BACKGROUND: For N1b papillary thyroid carcinoma (PTC) patients, lateral neck dissection encompassing levels Ⅱ-Ⅴ is generally recommended. However, routine level Ⅱ dissection is controversial given the low incidence of metastasis, and potential complications such as increased shoulder syndrome. METHODS: Retrospective analysis of consecutive patients with papillary thyroid carcinoma who underwent lateral neck dissection at a single institution from January 2019 to April 2021 was performed. Clinicopathological features such as age, gender, tumor location, tumor size, TgAb and TPOAb levels, capsular invasion, multifocality and lymph node metastases were examined to evaluate the occurrence of metastatic Level Ⅱ lymph nodes. RESULTS: Overall and occult level Ⅱ metastases were observed in 51.83% and 34.84% of cN1b PTC patients. Multivariant analysis showed that primary tumor, location of primary tumor and positive level Ⅴ can serve as independent risk factors of metastasis in level Ⅱ. For cN1b PTC patients not suspected of level Ⅱ lymph nodes preoperatively, independent risk factors for predicting occult level Ⅱ metastases may include the location of primary tumor, positive level Ⅲ and positive level Ⅴ. CONCLUSION: A significant number of patients with PTC and lateral neck disease experienced Level Ⅱ metastasis, with the location of primary tumor and multilevel lymph node involvement being the independent risk factors. If the tumor is less than 1 cm and located at lower 2/3 lobe, there is minimal possibility of level Ⅱ lymph node metastasis.

Comparison of Proteomics Profiles Between Xenografts Derived from Cell Lines and Primary Tumors of Thyroid Carcinoma.

Patient-consistent xenograft model is a challenge for all cancers but particularly for thyroid cancer, which shows some of the greatest genetic divergence between human tumors and cell lines. In this study, proteomic profiles of tumor tissues from patients, included anaplastic thyroid carcinoma (ATC) and papillary thyroid carcinoma, and xenografts (8305C, 8505C, FRO, BAPAP and IHH4) were obtained using HPLC-tandem mass spectrometry and compared based on all proteins detected (3,961), cancer-related proteins and druggable proteins using pairwise Pearson's correlation analysis. The human tissue showed low proteomic similarity to the ATC cell lines (8305C, r = 0.344-0.416; 8505C, 0.47-0.579; FRO, 0.267-0.307) and to PTC cell lines (BCPAP, 0.303-0.468; IHH4, 0.262-0.509). Human tissue showed the following similarity to cell lines at the level of 135 cancer-related pathways. The ATC cell lines contained 47.4% of the cancer-related pathways (19.26%-33.33%), while the PTC cell lines contained 40% (BCPAP, 25.93%; IHH4, 28.89%). In patient tumor tissues, 44-60 of 76 and 52-53 of 93 druggable proteins were identified in ATC and PTC tumors, respectively. Ten and 29 druggable proteins were not identified in any of the ATC and PTC xenografts, respectively. We provide a reference for CDX selecting in in vivo studies of thyroid cancer.

Predictive Risk-scoring Model For Central Lymph Node Metastasis and Predictors of Recurrence in Papillary Thyroid Carcinoma.

There are about half of papillary thyroid carcinoma (PTC) patients with the experience of central lymph node metastasis (CLNM), while the model to predict high-risk groups of CLNM from PTC patients is uncertain. The aim of this study was to evaluate candidate risk factors of CLNM and identify risk factors of recurrence to guide the postoperative therapeutic decision and follow-up for physicians and patients.A total of 4107 patients(4884 lesions) who underwent lymph node dissection in two hospitals from 2005 to 2014 were evaluated. CLNM risk was stratified and a risk-scoring model was developed on the basis of the identified independent risk factors for CLNM. Cox's proportional hazards regression model was used to investigate the risk factors for recurrence.CLNM was proved in 37.96% (1559/4107) of patients and 33.96% (1659/4884) of lesions. In the multivariate analysis, Male, Age ≤35 years, Tumor size >0.5 cm,Lobe dissemination (+), Psammoma body (+), Multifocality and Capsule invasion (+) were independent risk predictors of CLNM (P < 0.01). A 14-point risk-scoring model was built to predict the stratified CLNM in PTC patients and the area under receiver operating characteristic curve of the model for the prediction of CLNM was 0.672 (95% CI: 0.656-0.688) (P < 0.01). COX regression model showed that Tumor size >0.5 cm, Lobe dissemination (+), Multifocality and CLNM were significant risk factors associated with poor outcomes. The research suggested that prophylactic CLN dissection could be performed in patients with total score ≥4 according to the risk-scoring model, and more aggressive treatment and more frequent follow-up should be considered for patients with Tumor size >0.5 cm, Lobe dissemination (+), Multifocality and CLNM.

Preliminary screening and analysis of metastasis-related lncRNA and co-expressed papillary thyroid carcinoma mRNA.

The objective of the present study was to investigate the long non-coding RNA (lncRNA) and mRNA expression profiles that are associated with the invasion and metastasis of papillary thyroid carcinoma (PTC). Transwell invasion assays were used to screen three highly invasive sub-strains of the human PTC IHH4 cell line: IHH4-M1, IHH4-M2 and IHH4-M3. In addition, tumor-bearing nude mice were used to identify the invasive and metastatic capacity of the three sub-strains. Agilent lncRNA microarray chips were used to screen 795 differentially expressed lncRNAs and 788 differentially expressed mRNAs. A total of 10 lncRNAs and 10 mRNAs were randomly selected for RT-qPCR validation to confirm that the results were consistent with the microarray chips, suggesting that the results of the microarray chip analysis were relatively accurate. Gene ontology enrichment-based cluster analysis revealed that the differentially expressed genes were mainly associated with steroid biosynthesis, bioadhesion, intercellular adhesion and other metastasis-associated biological processes. The results of the pathway cluster analysis identified that the differentially expressed genes were associated with tumor metastasis-associated signaling pathways, including the cholesterol metabolic signaling pathway, the sterol regulatory element-binding protein signaling pathway and the integrin signaling pathway, suggesting that lncRNA may regulate PTC metastasis through various signaling pathways. The present study screened and constructed PTC metastasis-associated lncRNA and mRNA expression profiles, and it provides a molecular basis for the future study of high-risk molecular markers of PTC.

Expression and prognostic significance of MCM-3 and MCM-7 in salivary adenoid cystic carcinoma.

This study sought to investigate minichromosome maintenance protein 3 (MCM3) and minichromosome maintenance protein 7 (MCM7) expression in salivary adenoid cystic carcinoma (SACC) samples, and to evaluate the relationship between clinicopathological characteristics and prognosis. The expressions of MCM3 and MCM7 were evaluated using immunohistochemistry of tissue sections from SACC patients, and statistical analyses were performed to evaluate the associations between MCM expression and clinicopathological variables and to analyze the disease-free survival (DFS) and prognostic factors. The positive expression rates of MCM3 and MCM7 in SACC were 98.8% and 96.6%, respectively. MCM3 expression correlated with T-stage and nerve invasion. MCM7 expression correlated with T-stage, adjacent tissue invasion, nerve invasion, and prognosis, and was negatively associated with DFS. However, there was no significant correlation between MCM3 expression and DFS. A kappa analysis demonstrated that MCM3 was closely associated with MCM7. MCM7 may be a favorable prognosis indicator in SACC.

The significance of Delphian lymph node in papillary thyroid cancer.

AIM: To investigate the clinical significance of the DLN metastasis in papillary thyroid cancer (PTC). METHODS: A total of 231 PTC patients who underwent first surgical treatment in the Department of Hand and Neck Surgery of Zhejiang Cancer Hospital from January 2013 to June 2014 were enrolled. The relationship between Delphian lymph node (DLN) metastasis and patient age, gender, tumor size, tumor number, unilateral or bilateral, capsular invasion, pretracheal and paratracheal node metastasis, and lateral node metastasis was analyzed. RESULTS: Within 231 cases, 69 showed DLN, but only 19 (8.23%) were found with metastasis. In the univariate analysis, DLN metastasis was significantly associated with tumor size (P = 0.023), capsular invasion (P = 0.001), pretracheal or paratracheal node metastasis (P = 0.003) and lateral node metastasis (P = 0.001), while there were no significant correlation between DLN metastasis and gender (P = 0.976), age (P = 0.976), tumor number (P = 0.234) and unilateral or bilateral (P = 0.724). In the multivariate analysis, capsular invasion was an independent risk factor of DLN metastasis (P < 0.05, odds ratio = 10.15). CONCLUSION: Capsular invasion is an independent risk factor of DLN metastasis and DLN metastasis could be used as a predictor of lateral node metastasis. The dissection of DLN in PTC patients is recommended and lateral lymph node should be evaluated for patients with DLN positive.

miR-21 regulates tumor progression through the miR-21-PDCD4-Stat3 pathway in human salivary adenoid cystic carcinoma.

miR-21, which is a putative tumor onco-miR and frequently overexpressed microRNA in various tumors, has been linked to tumor progression through targeting of tumor-suppressor genes. In this study, we sought to determine whether miR-21 has any role on tumor progression of salivary adenoid cystic carcinoma (SACC) and the possible mechanisms. We found that the level of miR-21 expression was significantly higher in SACC than that in normal salivary tissues, and it is also higher in tumors with metastasis than that without metastasis. Using an anti-miR-21 inhibitor in an in vitro model, downregulation of miR-21 significantly decreased the capacity of invasion and migration of SACC cells, whereas a pre-miR-21 increased the capacity of invasion and migration of SACC cells. To explore the potential mechanisms by which miR-21 regulate invasion and migration, we identified one direct miR-21 target gene, programmed cell death 4 (PDCD4), which has been implicated in invasion and metastasis. The suppression of miR-21 in metastatic SACC-LM cells significantly increased the report activity of PDCD4 promoter and the expression of PDCD4 protein. This subsequently resulted in downregulation of the p-STAT3 protein. The level of miR-21 expression positively related to the expression of PDCD4 protein and negatively related to the expression of p-STAT3 protein in SACC specimens, respectively, indicating the potential role of the STAT3-miR-21-PDCD4 pathway in these tumors. Dysregulation of miR-21 has an important role in tumor growth and invasion by targeting PDCD4. Therefore, suppression of miR-21 may provide a potential approach for the treatment of advanced SACC patients.

Circulating miRNAs is a potential marker for gefitinib sensitivity and correlation with EGFR mutational status in human lung cancers.

miRNA expression is deregulated in non-small cell lung cancer (NSCLC), and some miRNAs are associated with gefitinib sensitivity. Here, we investigated if circulating miRNAs could be a useful biomarker for the prediction of EGFR mutation and the patient's prognosis. The differential miRNAs related to gefitinib sensitivity were screened and identified by microRNA array. Using Taqman-based real-time RT-PCR, we analyzed the expression of selected miRNAs in tumor tissues and plasma of 150 NSCLC patients. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to determine the association between miRNAs expression and survival. Receiver operating characteristic curve analysis was also performed. Compared with PC9 cell line, 41 microRNAs detected by microarray were significantly differentially expressed in A549 and H1299 cells. The 5 selected hsa-miRNAs were all found differently expressed between wild and mutant EGFR carriers (all P<0.01). Down-regulation of 5 selected miRNAs were independently associated with lymphatic invasion (all P<0.01) and clinical stage (all P<0.01), respectively. Both down-regulation of has-miR-195 (P=0.012) and has-miR-21 (P=0.004) were associated with poor differentiation. All up-regulation of 5 has-miRNAs were associated with smoking (All P<0.05). 5 hsa-miRNAs were up-regulated both in plasma and tissue samples. A model including 4 hsa-miRNAs may predict EGFR mutational status and gefitinib-sensitivity (both AUC: 0.869). Plasma levels of has-miR-125b expression were associated with disease-free survival (P=0.033) and overall survival in the patients (P=0.028). In a word, Circulating 5 selected miRNAs may especially be useful in predicting EGFR mutation, and circulating hsa-miR-125b may have prognostic values in NSCLC patients.

Abnormal Expression of DNA Double-Strand Breaks Related Genes, ATM and GammaH2AX, in Thyroid Carcinoma.

ATM and γH2AX play a vital role in the detection of DNA double-strand breaks (DSB) and DNA damage response (DDR). This study aims to investigate ATM and γH2AX expression in thyroid cancer and discuss possible relationship between thyroid function tests and DNA damage. The expression of ATM and γH2AX was detected by immunohistochemistry in 30 cases of benign nodular goiter, 110 cases of well differentiated thyroid cancer, 22 cases of poorly differentiated thyroid cancer, and 21 cases of anaplastic thyroid cancer. Clinicopathological features, including differentiation stages, distant metastasis, lymph node metastasis, T classification, TNM stage, and tests of thyroid functions (TPOAb, Tg Ab, T3, FT3, T4, FT4, TSH, and Tg), were reviewed and their associations with γH2AX and ATM were analyzed. γH2AX and ATM expressed higher in thyroid cancer tissues than in benign nodular goiter and normal adjacent tissues. γH2AX was correlated with ATM in thyroid cancer. Both γH2AX and ATM expression were associated with FT3. γH2AX was also associated with T classification, TNM stage, FT4, TSH, and differentiation status. Therefore both of ATM and γH2AX seem to correlate with thyroid hormones and γH2AX plays a role in the differentiation status of thyroid cancer.

Topo2A as a prognostic biomarker for patients with resectable esophageal squamous cell carcinomas.

Topoisomerase 2α (Topo2A) is a key enzyme in replication. It functions as a cell proliferation and cell cycle-specific marker and it is identified mainly in the interphase nuclei of proliferating cells. Many studies have shown that Topo2A protein expression is up-regulated in various cancers including esophageal cancer. However, to date, no studies have adequately addressed the prognostic value of Topo2A in patients with resectable esophageal squamous cell carcinoma (ESCC). Therefore, we conducted a large-scale retrospective study investigating the expression of Topo2A and the clinicopathological characteristics or prognosis of ESCC patients. Eight hundred and twenty-nine specimens of ESCC from patients who underwent complete esophageal cancer resection were evaluated using an immunohistochemical assay. Among them, 404 (48.7 %) cases with a score >2 were determined to be positive for Topo2A expression. Topo2A overexpression was significantly associated with poorer differentiation (P = 0.007) and perineural invasion (P = 0.046). The median progression-free survival (PFS) of 319 patients with Topo2A-positive expression and 336 patients with Topo2A-negative expression was 19.5 and 26.5 months, respectively (P = 0.000). The overall survival (OS) in patients with and without Topo2A expression was 34.0 and 44.5 months, respectively (P = 0.002). In the multivariate analysis, Topo2A overexpression was identified as an independent prognostic factor for PFS (P = 0.001) and OS (P = 0.009). We determined that Topo2A overexpression was not only associated with poorer differentiation and perineural invasion, but it could also act as an independent risk factor for ESCC.

Clinical Characteristics Related to Central Lymph Node Metastasis in cN0 Papillary Thyroid Carcinoma: A Retrospective Study of 916 Patients.

Background. Papillary thyroid carcinoma (PTC) is a form of thyroid cancer with high risk of cervical lymph node metastasis. Aim. The aim of this study was to investigate the incidence and the predictive factors for occult ipsilateral central lymph node (CLN) metastasis in the patients with papillary thyroid carcinoma. Methods. A total of 916 PTC patients (1017 lesions) undergoing central lymph node dissection in our hospital from 2005 to 2011 were enrolled. The relationship between CLN metastasis and clinical factors such as gender, age, tumor size, tumor number, capsule invasion, and tumor location was analyzed. Results. Occult CLN metastasis was observed in 52.41% (533/1017) of PTC lesions, respectively. Multivariate analysis showed that age ≤ 35 years, tumor size > 1.5 cm, present capsule invasion/extracapsular invasion, and tumor located in upper/middle pole/whole lobe were risk factors of CLN metastasis. Conclusions. Tumor located in upper/middle pole/whole lobe, less than 35 years old, tumor size > 1.5 cm, and present capsule invasion/extracapsular invasion were risk factors of CLN metastasis. We recommend performing ipsilateral prophylactic CLN dissection in cN0 PTC patients.

Pim-1 acts as an oncogene in human salivary gland adenoid cystic carcinoma.

BACKGROUND: Pim-1 (Provirus integration site for Moloney murine leukemia virus 1) belongs to the Ser/Thr kinase family and plays a pivotal role in occurrence and development of oncogenesis. Recent studies have demonstrated that Pim-1 phosphorylates RUNX3 and alters its subcellular localization. However, few studies have concerned the implications of Pim-1 in the salivary gland adenoid cystic carcinoma (ACC). In this study, we aimed to clarify the function of Pim-1 in ACC in vitro. Meanwhile, we measured the levels of Pim-1 and RUNX3 in the ACC tissues. The correlations between Pim-1/RUNX3 levels and clinical parameters were also analyzed. METHODS: SACC-83 and SACC-LM cells were transfected with the Pim-1 siRNA. Pim-1 mRNA and protein expression were measured using real-time PCR and immnuoblot, respectively. Cell proliferation was analyzed by CCK-8 assay. Cell cycle, apoptosis, and mitochondrial membrane potential were detected by flow cytometry. Effects of Pim-1 on cells' invasion were evaluated by transwell migration assay. Pim-1 and RUNX3 levels in ACC tissues were examined by immunohistochemistry. RESULTS: Pim-1 siRNA reduces cell proliferation, induces apoptosis, causes cell cycle arrest through cell cycle related proteins (Cyclin D1 and CDK4), mitochondrial depolarization, and decreases invasive ability in SACC-83 and SACC-LM cells. Pim-1 and RUNX3 levels are significantly relevant and associated with T-stage and nerve invasion in the ACC tissues. CONCLUSIONS: This study demonstrates the oncogenic role of Pim-1 in ACC. The findings also suggest that Pim-1 may serve as a neoteric therapeutic target and potential prognostic marker for ACC cancer.