Occurrence Of Lymph Node Metastasis Research Articles

Evaluation of Risk Factors for Distant and Lymph Node Metastasis of Pancreatic Neuroendocrine Tumors.

PurposeMetastases of pancreatic neuroendocrine tumors (pNETs) can be found at the time of diagnosis in 20–50% of cases. Small asymptomatic tumors may be left for observation; however, they can metastasize. The aim of the study was to evaluate risk factors for distant and lymph node metastases of pNETs.Patients and methodsOne hundred and fourteen patients with postoperatively confirmed pNET were analyzed retrospectively in a single ENETS Center of Excellence. The relationship between location, size, differentiation of the tumor, and occurrence of lymph node and distant metastases was analyzed.ResultspNETs’ location was pancreatic head – 38 (33.3%), body or tail – 68 (59.7%), and 8 (7.0%) involved the entire organ. Fifty-six (49.1%) tumors were graded G1, 50 (43.9%) G2, and 8 (7.0%) G3. Seventy-two (63.2%) tumors were ≥2 cm in diameter, and 42 (36.8%) <2 cm. Twenty-two (19.3%) patients had distant metastases and 47 (41.2%) had lymph node metastases. In ≥2 cm tumors distant and lymph node metastases were more frequent (p < 0.05). Distant metastases incidence was significantly higher in distally located tumors (p = 0.01) and in G2 and G3 tumors (p < 0.01). In 9.5% of <2cm tumors, distant metastases were present at diagnosis.ConclusionDistant metastases are more often found in larger, distally located pNETs grade G2 and G3, while a higher occurrence of lymph node metastases seems to be associated only with larger tumor size. A considerable number of tumors <2 cm in size have distant metastases already at the diagnosis, which might indicate the need for careful qualification of smaller lesions for observation.

SENP1 Aberrance and Its Linkage to Clinical Features, Adjuvant Regimen, and Prognosis in Patients With Surgical Non-small Cell Lung Cancer Receiving Adjuvant Chemotherapy.

BackgroundSmall ubiquitin-like modifier-specific protease 1 (SENP1) plays vital roles in cancer progression and chemoresistance, but its prognostic value in non-small cell lung cancer (NSCLC) is vague. This study aimed to explore the correlation of SENP1 with clinical features, adjuvant chemotherapy regimen, and prognosis in patients with surgical NSCLC receiving adjuvant chemotherapy.MethodsTumor and adjacent tissues were collected from 157 patients with surgical NSCLC receiving adjuvant chemotherapy. Meanwhile, tumor tissue and paired adjacent tissue specimens were obtained to evaluate SENP1 protein expression by immunohistochemistry (IHC) assay; among which, 102 pairs were used to detect SENP1 messenger RNA (mRNA) by reverse transcription quantitative PCR.ResultsSENP1 IHC score and SENP1 mRNA expression were increased in tumor tissue than adjacent tissue (p < 0.001). Besides, elevated SENP1 IHC score was correlated with > 5 cm tumor size (p = 0.045), lymph node metastasis occurrence (p = 0.003), and advanced tumor-node-metastasis (TNM) stage (p = 0.012); meanwhile, increased SENP1 mRNA expression was associated with histopathological subtype (p = 0.011), lymph node metastasis occurrence (p = 0.008), and higher TNM stage (p = 0.015). Besides, no correlation was found in SENP1 IHC score (p = 0.424) or mRNA expression (p = 0.927) with specific adjuvant chemotherapy regimen. Additionally, both the SENP1 protein (high) (p = 0.003) and mRNA high (p = 0.028) were correlated with poor disease-free survival (DFS), while SENP1 protein high was also associated with shorter overall survival (OS) (p = 0.029). Furthermore, SENP1 protein (high vs. low) was independently associated with unsatisfying DFS [p = 0.009, hazard ratio (HR) = 1.798] and OS (p = 0.049, HR = 1.735).ConclusionSENP1 may serve as a potential biomarker to improve the management of patients with surgical NSCLC receiving adjuvant chemotherapy.

The Role of the Adipokine Resistin in the Pathogenesis and Progression of Epithelial Ovarian Cancer.

Obesity is a civilization disease associated with an increased risk of developing cardiovascular diseases, diabetes, and some malignancies. The results concerning the relationship between obesity and epithelial ovarian cancer (EOC) are inconclusive. The higher incidence of neoplasms in obese subjects has led to the development of the adipokine hypothesis. Omental adipocyte cells interact with cancer cells, promoting their migration and metastasis via the secretion of adipokines, growth factors, and hormones. One of the adipokines is resistin. It was shown in vitro that resistin stimulates the growth and differentiation of ovarian cancer cells. Moreover, it increases the level of angiogenesis factors, e.g., matrix metalloproteinase 2 (MMP-2) and vascular epithelial growth factor (VEGF). Additionally, resistin induces epithelial–mesenchymal transition (EMT) and stemness in EOC cell lines. A positive correlation has been shown between a higher level of resistin expression and the stage of histological differentiation of EOC or the occurrence of lymph node metastases. In addition, the overexpression of resistin has been found to act as an independent factor determining disease-free survival as well as overall survival in EOC patients. Growing evidence supports the finding that resistin plays an important role in some mechanisms leading to the progression of EOC, though this issue still requires further research.

The Construction and Development of a Clinical Prediction Model to Assess Lymph Node Metastases in Osteosarcoma.

Background: This study aimed to construct a clinical prediction model for osteosarcoma patients to evaluate the influence factors for the occurrence of lymph node metastasis (LNM).Methods: In our retrospective study, a total of 1,256 patients diagnosed with chondrosarcoma were enrolled from the SEER (Surveillance, Epidemiology, and End Results) database (training cohort, n = 1,144) and multicenter dataset (validation cohort, n = 112). Both the univariate and multivariable logistic regression analysis were performed to identify the potential risk factors of LNM in osteosarcoma patients. According to the results of multivariable logistic regression analysis, A nomogram were established and the predictive ability was assessed by calibration plots, receiver operating characteristics (ROCs) curve, and decision curve analysis (DCA). Moreover, Kaplan-Meier plot of overall survival (OS) was plot and a web calculator visualized the nomogram.Results: Five independent risk factors [chemotherapy, surgery, lung metastases, lymphatic metastases (M-stage) and tumor size (T-stage)] were identified by multivariable logistic regression analysis. What's more, calibration plots displayed great power both in training and validation group. DCA presented great clinical utility. ROCs curve provided the predictive ability in the training cohort (AUC = 0.805) and the validation cohort (AUC = 0.808). Moreover, patients in LNN group had significantly better survival than that in LNP group both in training and validation group.Conclusion: In this study, we constructed and developed a nomogram with risk factors, which performed well in predicting risk factors of LNM in osteosarcoma patients. It may give a guide for surgeons and oncologists to optimize individual treatment and make a better clinical decision.

Correlation between Pre-Operative 25-Hydroxyvitamin D Levels and Poor Prognostic Factors for Papillary Thyroid Cancer

Purpose To evaluate the relationship between pre-operative 25-hydroxyvitamin D (25 (OH) D) levels and poor prognostic factors for papillary thyroid cancer (PTC). Methods A total of 1161 patients diagnosed with PTC were analyzed retrospectively. The patients were categorized .based on their pre-operative 25 (OH) D levels into three groups: the severe vitamin D deficiency (VDD) group (25 (OH) D < 10 ng/mL), moderate VDD group (20 ng/mL > 25 (OH) D ≥ 10 ng/mL), and control group (25(OH)D ≥ 20 ng/mL) Differences in the demographic and clinicopathological characteristics among the three groups were analyzed. Linear and logistic regression analyses were also performed to determine the effect of 25 (OH) D levels on the established poor prognostic factors for PTC. Results We observed a negative correlation between 25 (OH) D levels and tumor size (r = −0.067, P = 0.049). Severe VDD and moderate VDD were independently associated with lymph node metastasis and distant metastasis diagnosed during surgery (P = 0.00, odds ratio (OR) = 4.11; P = 0.00, OR = 3.33, respectively). After adjusting parameters such as sex, age, body mass index, and thyroid-stimulating hormone (TSH) levels, severe VDD and moderate VDD were found to be closely associated with advanced cancer stage (stage III or IV) (P = 0.018, OR = 3.02; P = 0.041, OR = 3.60, respectively). Additionally, a significant correlation (P = 0.007) was observed between the pre-operative 25 (OH) D and TSH levels. Conclusion 25 (OH) D levels were significantly associated with certain poor prognostic factors for PTC, including larger tumor diameter and the occurrence of lymph node metastasis. More prospective studies are needed to evaluate whether the assessment and supplementation of vitamin D contributes to the pre-operative management of patients with PTC.

14-3-3ζ promoted invasion and lymph node metastasis of breast invasive ductal carcinoma with HER2 overexpression

BackgroundHER2 was a recognized oncogene that promoted the development and metastasis of breast cancer, but its positive expression rate in invasive ductal carcinoma (IDC) was much lower than that in ductal carcinoma in situ (DCIS). The correlation between the occurrence and development of breast cancer and the amplification and overexpression of HER2 gene alone was still controversial. 14–3–3ζ had a strong protein binding ability and a variety of functions, mainly through the interaction with other proteins to exert its unique biological activities. However, influence and interaction relationship of the two proteins on the development of IDC was not clear. Furthermore, the mutual effect mechanism of synergy effect on lymph node metastasis of IDC was not known well too. MethodsImmunohistochemistry experiment was performed to detect expression status of 14–3–3ζ, HER2, TGF-β, p53 and Gli2 in paraffin-embedded samples respectively, including 30 cases of normal breast tissue, 30 cases of usual ductal hyperplasia (UDH), 30 cases of atypical ductal hyperplasia (ADH), 30 cases of DCIS and 120 cases of IDC. ResultsThe positive expression rates of 14–3–3ζ/HER2 in Normal group, UDH group, ADH group, DCIS group and IDC group were 30%/0.00%, 26.7%/0.00%, 53.3%/33.3%, 46.7%/53.3% and 50%/24.2%, respectively. Compared with Normal group or UDH group, the expression of 14–3–3ζ was significantly increased in ADH, DCIS and IDC groups. 14–3–3ζ was overexpressed in only 4 of the 16 DCIS cases with HER2 overexpression (25.0%, 4/16), but it was overexpressed in 7 of the 9 IDC cases with DCIS (77.8%, 7/9). Among HER2 overexpression cases, 14–3–3ζ overexpression was significantly different between DCIS group and IDC with DCIS group (P = 0.017). In 18 IDC cases with lymph node metastasis and HER2 overexpression, 14–3–3ζ was overexpressed in 15 cases (83.3%, 15/18), while in the 11 IDC cases without lymph node metastasis, 14–3–3ζ and HER2 were overexpressed in only 5 cases (45.5%, 5/11). Co-overexpression of 14–3–3ζ and HER2 was positively correlated with occurrence of lymph node metastasis (P = 0.048). TGF-β was overexpressed in both precancerous lesion group and IDC group compared with normal group. Compared with the IDC group without lymph node metastasis, TGF-β expression was significantly increased in the IDC group with lymph node metastasis (P = 0.015). In IDC cases with 14–3–3ζ and HER2 co-overexpression, the expression of p53 in IDC with lymph node metastasis was significantly decreased (P = 0.010), while the expression of Gli2 was significantly increased compared with IDC cases without lymph node metastasis (P = 0.038). The co-overexpression of 14–3–3ζ and HER2 was positively correlated with ER negative expression (P < 0.001) and PR negative expression (P = 0.038), respectively. Conclusion14–3–3ζ synergistic with HER2 could promote the occurrence and development of breast IDC and induce the lymph node metastasis of IDC, suggesting that combined overexpression of 14–3–3ζ and HER2 would lead to higher invasion and metastasis risk of breast cancer. It was speculated that the combined detection of 14–3–3ζ and HER2 would be one of the key factors affecting the clinical treatment decision and prognosis.

Fatty Acid Receptor CD36 Functions as a Surrogate Parameter for Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Simple SummaryThe frequent occurrence of occult cervical lymph node metastasis is still a therapeutic challenge in oral squamous cell carcinoma (OSCC) and represents a limiting factor in terms of survival. The common staging of malignancy is not precise enough to predict the development of lymph node metastases and additional prognostic factors are needed. In this study we show that CD36, a protein related to fatty acid metabolism, is expressed in OSCC and correlates with the occurrence of lymph node metastasis. CD36 may be useful as a specific parameter for lymph node metastasis and as a progression parameter for survival. Therefore, CD36 could be useful for risk stratification regarding lymph node metastasis in OSCC and, beyond that, CD36 could also be a possible therapeutic target in future.Purpose: To investigate the expression pattern of CD36 in a patient population with oral squamous cell carcinoma (OSCC) and to correlate CD36 expression with clinical and histopathological parameters. The hypothesis was that CD36 expression correlates with the occurrence of lymph node metastasis. Methods: To address the study objectives, a retrospective cohort study was conducted. Study variables included demographic, histopathological and survival data. CD36 expression patterns were assessed by immunohistochemistry on tissue microarrays (TMA). Logistic regression analysis, survival analysis and Cox proportional hazards model were performed. Results: High CD36 expression correlated significantly with a higher T-status, grading and occurrence of lymph node metastasis. The logistic regression with binary N status as a dependent variable showed that high CD36 expression increased the chance for lymph node metastasis 45-fold (OR = 44.7, 95% CI: 10.0–316). Patients with high CD36 expression had lower probabilities of progression-free survival. CD36 had a small and non-significant independent influence on progression-free survival. Conclusions: CD36 is expressed in OSCC and correlates with tumor grading, T-status, and especially the occurrence of lymph node metastasis. CD36 may be useful for risk stratification regarding lymph node metastasis in OSCC.

Peripheral Versus Intraparenchymal Papillary Thyroid Microcarcinoma: Different Morphologies and PD-L1 Expression.

Peripheral localisation of papillary thyroid microcarcinoma (PTMC), in comparison with intraparenchymal PTMC (i-PTMC) is related to some clinicopathological features related with biological aggressiveness, including lymph node metastasis (LNM). The expression of PD-L1 in tumour cell has been associated with increased tumour survival, progression, and potentially an aggressive clinical course. This study evaluates the relation between clinicopathological features of PTMC, including tumour localisation, with PD-L1 immunoexpression. The study included 99 patients with the histological diagnosis of PTMC (≥ 5mm). PD-L1 protein expression was assessed by immunohistochemistry. PTMCs were divided into the four following groups: G1- peripherally localised PTMC (p-PTMC) with PD-L1 expression; G2-p-PTMC without PD-L1 expression; G3-i-PTMC with PD-L1 expression and G4-i-PTMC without PD-L1 expression. G1 was the most frequent (n = 46; 46.5%), followed by G4 (n = 25; 25.3%) and similar distribution of G3 (n = 15; 15.2%) and G2 (n = 13; 13.1%). In comparison with other groups, G1 was significantly associated with classical morphology, invasive growth, lymphatic invasion (LI), vascular invasion (VI), psammoma bodies, intratumoral fibrosis, PD-L1 positive tumour-infiltrating lymphocytes, and multinuclear giant cells (MGCs). G4 more commonly exhibited follicular morphology, expansive/circumscribed growth, and absence of the following: intratumoural fibrosis, LI, VI, psammoma bodies, PD-L1 positive tumour-infiltrating lymphocytes, and MGCs. LNMs were significantly more frequent in G1 in comparison with the other groups (p = 0.000). In conclusion, morphology and tumour microenvironment of p-PTMC with PD-L1 expression is different from i-PTMC without PD-L1 expression. The differences between these two groups of PTMC include clinicopathological features related with biological aggressiveness such as the occurrence of LNM.

Endoscopic resection of Barrett's adenocarcinoma: Intramucosal and low-risk tumours are not associated with lymph node metastases.

BackgroundSuperficial oesophageal adenocarcinoma can be resected endoscopically, but data to define a curative endoscopic resection are scarce.ObjectiveOur study aimed to assess the risk of lymph node metastasis depending on the depth of invasion and histological features of oesophageal adenocarcinoma.MethodsWe retrospectively included all patients undergoing an endoscopic resection for T1 oesophageal adenocarcinoma among seven expert centres in France in 2004–2016. Mural invasion was defined as either intramucosal or submucosal tumours; the latter were further divided into superficial submucosal (<1000 mm) and deep submucosal (>1000 mm). Absence or presence of lymphovascular invasion and/or poorly differentiated cancer (G3) defined a low‐risk or a high‐risk tumour, respectively. For submucosal tumours, invasion depth and histological features were systematically confirmed after a second dedicated histological assessment (new 2‐mm thick slices) performed by a second pathologist. Occurrence of lymph node metastasis was recorded during the follow‐up from histological or PET CT reports when an invasive procedure was not possible.ResultsIn total, 188 superficial oesophageal adenocarcinomas were included with a median follow‐up of 34 months. No lymph node metastases occurred for intramucosal oesophageal adenocarcinomas (n = 135) even with high‐risk histological features. Among submucosal oesophageal adenocarcinomas, only tumours with lymphovascular invasion or poorly differentiated cancer or with a depth of invasion >1000 μm developed lymph node metastasis tumours (n = 10/53%; 18.9%; hazard ratio 12.04). No metastatic evolution occurred under a 1000‐mm threshold for all low‐risk tumours (0/25), nor under 1200 mm (0/1) and three over this threshold (3/13%, 23.1%).ConclusionIntramucosal and low‐risk tumours with shallow submucosal invasion up to 1200 mm were not associated with lymph node metastasis during follow‐up. In case of high‐risk features and/or deep submucosal invasion, endoscopic resections are not sufficient to eliminate the risk of lymph node metastasis, and surgical oesophagectomy should be carried out. These results must be confirmed by larger prospective series.

Collagen type 1 alpha 1 chain is a novel predictive biomarker of poor progression-free survival and chemoresistance in metastatic lung cancer.

Background: Collagen type 1 alpha 1 chain (COL1A1) is an extracellular matrix protein comprising two alpha 1 chains and one alpha 2 chain. Our previous study identified that COL1A1 is the key gene during the development and progression of lung adenocarcinoma by multi-omics analysis. However, the clinical significance of COL1A1 expression in lung cancer samples remains largely unknown. Here, we aimed to evaluate the level of COL1A1 in lung cancer samples and correlate its level with the clinical outcome.Methods:COL1A1 gene expression in lung cancer samples was analyzed using the Oncomine database (www.oncomine.org). A total of 308 lung cancer samples (208 formalin-fixed paraffin-embedded tissues and 100 blood samples) were assessed for protein expression of COL1A1. Immunohistochemistry staining and enzyme-linked immunosorbent assay were used to detect COL1A1 expression in tissues and serum, respectively.Results: We identified an elevation of COL1A1 in mRNA level and gene amplification in lung cancer tissues compared with normal lung tissues. High COL1A1 expression was observed in lung cancer tissues and serum (P < 0.05), it was significantly correlated with the peripheral type tumor, the larger diameter of the tumor, the occurrence of lymph node metastases and distant metastases, a higher TNM stage, and smoking (P < 0.05). High COL1A1 expression was associated with poor progression-free survival (PFS) and chemoresistance in lung cancer patients (P < 0.05). Multivariable Cox-regression analysis showed that COL1A1 expression was an independent prognostic factor (P < 0.05). Furthermore, the area under the receiver operating characteristic (AUC) curve was 0.909 for the combined COL1A1 and carcinoembryonic antigen (CEA) measurement.Conclusion: Our findings revealed that COL1A1 could be used as a novel diagnostic, prognostic, and chemoresistance biomarker of human lung cancer, and these results provide a potential therapeutic strategy for lung cancer patients.

Survival advantage of upfront cytoreductive nephrectomy in patients with primary metastatic renal cell carcinoma compared with systemic and palliative treatments in a real-world setting

Background Recently, the CARMENA and SURTIME studies, suggested that upfront cytoreductive nephrectomy (CN) should be abandoned for patients with intermediate and high-risk metastatic renal cell carcinoma (mRCC). However, CN remains an indication in low-risk and when immediate systemic treatment is not required. The aim was to evaluate the long-term overall survival (OS) in patients with primary mRCC, based on the first line treatment. Methods There were 1483 patients with primary mRCC in the National Kidney Cancer Registry from 2005 to 2013. Data on primary treatment, TNM stage, RCC type, tumor size, patient age and sex were extracted. Survival time was calculated from time of diagnosis to time of death or until July 2019. Mann-Whitney U and Chi-square tests, the Kaplan-Meyer method and Cox regression analyses were used. Results Patients primary treated with CN had a significantly longer OS (p < .001) than patients primary treated with systemic therapy or palliation. In a Cox regression multivariate analysis, the hazard ratio for CN compared with no CN was 1.600, 95%Ci (1.492 − 1.691), p < .001. Also occurrence of lymph node metastases, T-stage, patients age and year of diagnosis, remained as independent predictors of OS. Conclusion Patients primary treated with CN survived significantly longer than patients primary treated with systemic therapy or palliation, in all age groups. CN was an important first-line treatment option in mRCC patients.

Machine Learning Predicts Lymph Node Metastasis in Early-Stage Oral Tongue Squamous Cell Carcinoma

Early-stage oral tongue squamous cell cancer (OTSCC) has a rate of metastasis to the cervical lymph nodes of 20 to 50%. This study aimed to build and validate 4 machine learning (ML) models to predict the occurrence of lymph node metastasis before and after surgery for early-stage (cT1N0 to cT2N0) OTSCC. We designed a retrospective cross-sectional study and reviewed the clinical and pathologic records of patients with early-stage OTSCC. The sample was composed of 2 groups with different node status (positive or negative) and was randomly split into training (70%) and testing (30%) sets. Four common ML algorithms-logistic regression, random forest, support vector machine, and naive Bayes-were used to predict pathologic nodal metastasis of early-stage OTSCC. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to assess the performance of these models and conventional methods including depth of invasion (DOI), neutrophil-to-lymphocyte ratio (NLR), and tumor budding. A total of 145 patients (56 with positive and 89 with negative lymph nodes) were included in this study. The performance of ML models was significantly superior to that of conventional prediction methods. The random forest model performed best (AUC, 0.786; sensitivity, 85%; specificity, 75%) and exceeded the performance of NLR (AUC, 0.539; sensitivity, 53.6%; specificity, 53.9%; P=.003).When DOI, worst pattern of invasion, lymphocytic host response, and tumor budding were added to model analysis according to patients' postoperative pathologic records, the support vector machine model performed best (AUC, 0.956; sensitivity, 100%; specificity, 87.5%) and was superior to univariate assessment of tumor budding (AUC, 0.830; sensitivity, 80.9%; specificity, 87.5%, P=.002), DOI (AUC, 0.613; sensitivity, 91.1%; specificity, 31.5%; P<.001), and NLR. ML shows a better performance in predicting lymph node metastasis of early-stage OTSCC than conventional prediction methods of DOI, NLR, or tumor budding.

Regional Lymph Node Metastasis of Scalp Angiosarcoma: A Detailed Clinical Observation Study of 40 Cases.

The incidence of lymph node metastasis (LNM) of angiosarcomas is reported to be less than 15%, and elective neck management has not been indicated. This study evaluated the incidence and pattern of regional LNM in patients with scalp angiosarcomas using the clinical data of its full course to understand time-event sequences of scalp angiosarcomas. This retrospective study included all consecutive cases of pathology-confirmed angiosarcomas and analyzed 40 cases of scalp angiosarcomas. The survival plots were estimated using the Kaplan-Meier method, and the results are presented mainly in a descriptive manner. The overall survival rate for the patients was 35.8% at 2years. In contrast to previous reports, regional LNM was observed in more than half of the patients (52.5%) with scalp angiosarcoma. Meanwhile, a direct spread to distant organs occurred in only 27.5% of the patients. Regional LNM could predict clinical manifestation of systemic disease within 3 to 6months. No differences in survival rates between patients with and without LNM were observed in this series. Occurrence of LNM seemed to be correlated with a high mitotic rate of primary tumors, but not with tumor grade or tumor dimension. The first-echelon lymph nodes from scalp angiosarcoma were peri-parotid, post-auricular, and level 2 lymph nodes. For a localized scalp angiosarcoma, it seems reasonable for initial curative surgery to include prophylactic evaluation of regional lymph nodes for pathologic nodal staging, prognosis estimation, and the decision for systemic treatments.

Profiling of serum metabolites in advanced colon cancer using liquid chromatography-mass spectrometry.

Lymph node metastasis remains a key factor that affects the prognosis of patients with colon cancer. The aim of the present study was to identify and evaluate serum metabolites as biomarkers for the detection of tumor lymph node metastasis and the prediction of patient survival. The present study analyzed the metabolites in the serum of patients with advanced colon cancer both with and without lymph node metastasis. Blood samples from 104 patients with stage T3 colon cancer were collected and analyzed using liquid chromatography-mass spectrometry. The metabolites were structurally confirmed with data from the Human Metabolome Database. The association between the serum metabolites and the clinicopathological characteristics and survival time of patients from the present study was analyzed. Overall, 227 different metabolites were identified in the serum of patients with stage T3 colon cancer with or without lymph node metastasis. Furthermore, 17 of these metabolites may potentially distinguish those patients with lymph node metastasis from those patients without. In addition, five factors, including abscisic acid, calcitroic acid and glucosylsphingosine presence in the serum, age and sex, were identified as independent predictors for lymph node metastasis (P<0.05). Furthermore, three factors, including abscisic acid, calcitroic acid and glucosylsphingosine presence in the serum were independent predictors for patient survival (P<0.05). In conclusion, the serum levels of abscisic acid, calcitroic-acid and glucosylsphingosine may be considered as potential biomarkers to predict the occurrence of lymph node metastasis and the survival time of patients with colon cancer.

The Effects of Ezh2 Mutation on Kras‐Driven Adenocarcinoma

Lung cancer is the deadliest form of cancer worldwide. Non‐small cell lung cancer (NSCLC) is the most common type of lung cancer, constituting an estimated 84% of diagnoses. Conducting research regarding the metastasis of lung adenocarcinomas is especially pertinent, as the 5‐year survival rate for localized NSCLC is an estimated 50% versus 6% in metastatic lung cancer. Here we investigate the activation effects of Polycomb Repressive Complex 2 (PRC2), an epigenetic regulator commonly found to be dysregulated in human lung cancer, as a driver of metastasis. We employed genetically engineered mouse models harboring activating point mutations in Kras and inactivating mutations in the p53 pathway (KP model) which develop lung adenocarcinomas but exhibit low penetrance and long latency for metastasis. As a resolution, our lab has generated a KPE mouse model which carries a mutation that induces Ezh2 activation, a core component of PRC2. We hypothesize that KPE is an effective and robust metastatic model which displays a shorter latency period than previously established lung adenocarcinoma models. In this project we used a histological approach to characterize morphological properties of primary tumors as well as distinct lymph node metastases in KPE mouse models. By visualizing cellular phenotypes through Hematoxylin &amp; Eosin staining, we intended to quantify tumor area and composition of lymphatic micrometastases. The results illustrated that mice with the Ezh2 mutation in addition to the Kras and p53 mutations experienced a shorter latency period as well as a higher occurrence of lymph node metastases as opposed to the KP model.Support or Funding InformationThis project is supported in part by National Science Foundation Grant 1758007.

Cervical lymph node metastasis in adenoid cystic carcinoma of the salivary glands: A clinicopathologic study

To investigate the incidence and clinicopathologic features of cervical lymph node metastasis in salivary gland adenoid cystic carcinoma (AdCC). Retrospective analysis was made in 798 AdCC patients who underwent tumor resection during January, 2001 to January, 2019 in Peking University School and Hospital of Stomatology, especially the clincopathologic characteristics of 82 cases with lymph node metastasis. In the study, 82 of the 798 patients were identified with cervical lymph node metastasis, which was confirmed by histopathological examination. The palate, the region of sublingual gland and mouth floor, and the parotid were the frequently involved primary sites for AdCCs. The general incidence rate of lymph node metastasis was approximately 10%. The submandibular gland, the region of sublingual gland and mouth floor, and the mobile tongue were the most frequent sites of lymph node metastasis with the incidence rates of 20.8%, 16.1%, and 15.1%, respectively; while lymph node metastasis was uncommon in the tumors which were the origin from the palate and parotid, with incidence rates of 6.1% and 3.4%, respectively. Most AdCC cases (70.7%) showed the classic "tunnel-style" metastatic pattern of occurrence, and the level I and II regions were the most frequently involved areas. The 5-year and 10-year overall survival rates of the patients with lymph node metastasis were 77.4% and 20.6% respectively, while the 5-year and 10-year overall survival rates of the patients with no lymph node metastasis were 83.5% and 57.6%, respectively. The univariate analysis demonstrated that statistically significant differences in the overall survival for the presence of lymph node metastasis (P<0.001). In the meantime, the 5-year disease-free survival rate of the patients with lymph node metastasis also showed statistically significant differences to that of the AdCC patients with no lymph node metastasis. In addition, the primary site and histological grade were significantly associated with lymph node metastasis, and the high-grade solid growth pattern was identified as a strong predictor for the occurrence of lymph node metastasis. Cervical lymph node metastasis has a high tendency of occurrence in submandibular gland and tongue-mouth floor complex, and the high-grade solid growth pattern could be taken as a strong predictor for the occurrence of lymph node metastasis, which correlates to poor prognosis of AdCC patients. A selective neck dissection should be considered as a management in such patients.

A Clinical Study on the Expression of miR-195 in Cardiac Carcinoma

Background: Recently, some studies have revealed that microRNAs (miRs; miRNAs) mainly regulate gene expression in the transcription of microRNAs. However, the role of microRNAs in cell development, differentiation, proliferation, and other physiological processes remains unclear. Objectives: The present study aimed to investigate the expression level of microRNA-195 in the pathological tissues of patients with cardiac carcinoma and its clinical effects. Methods: Patients with primary cardiac carcinoma were enrolled as the study subjects. The tumor and adjacent tissue samples for cancer pathology were obtained during the operation. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of microRNA-195 and its correlation with the clinicopathological features of cardiac carcinoma was analyzed. Results: A total of 64 patients were included in this study. Firstly, the expression rate of miR-195 in cardiac carcinoma tissues showed a significant decreasing trend (3.65 ± 0.42 vs. 2.05 ± 0.33) (P < 0.001) and the actual expression level of miR-195 in pathological tissues of cardiac carcinoma was negatively correlated with the malignant degree of pathological tissues (P = 0.028), invasion (P = 0.037), and lymph node metastasis of cardiac carcinoma (P = 0.023), but miR-195 was not correlated with age (P = 0.615) and gender (P = 0.465). Conclusions: The expression of microRNA-195 is closely correlated to the severity of cardiac carcinoma and the occurrence of lymph node metastasis.

Pattern of Nodal Metastasis in Laryngeal Carcinoma

Aims: To find out the occurrence of lymph node metastasis, level of neck node involvement and the pattern of clinical presentation of patients suffering from laryngeal carcinoma.&#x0D; Methods: A cross-sectional study on 90 cases of laryngeal carcinoma was carried out in the inpatient department of Otolaryngology- Head and neck surgery of Dhaka Medical College Hospital, Dhaka during a period of two years. Smoking and chewing betel leaf and tobacco are the most important predisposing factors.&#x0D; Results: Most of the cases presented with more than one symptom. Change of voice was the commonest symptom. Cervical lymphadenopathy are significantly associated with supraglottic carcinoma. Level IV and level III is the commonest level of the lymph node involvement in laryngeal carcinoma.&#x0D; Bangladesh J Otorhinolaryngol; October 2017; 23(2): 109-114

Lymph node metastasis in extremity chondrosarcomas: A series of four cases.

Background:Primary bone sarcomas mainly metastasize through haematogenous route and rarely through lymph nodes due to paucity of lymphatic channels in the bone (1). Nodal spread in chondrosarcoma is extremely rare and there are two reported cases in literature including one previously published by our institute (3, 5).Aims and Objectives:We present a series of chondrosarcoma cases (primary tumour located in the scapula, proximal femur, proximal humerus and pelvis), presenting with lymph node metastasis, treated at our institute. We assessed the oncological outcome of these cases and the impact of nodal metastasis on survival.Materials and Methods:Between January 2006 and December 2015, 243 patients of extremity and pelvic chondrosarcoma were operated at our institute. These cases were retrieved from a prospectively maintained database. Four (1.6%) of these patients developed lymph node metastasis. Clinical and radiological details of these cases were retrieved from electronic medical records and case files. Histopathology of the primary chondrosarcoma lesion and nodal metastasis was reconfirmed by a pathologist specializing in sarcomas.Conclusion:Lymph node metastasis though extremely rare in primary osseous chondrosarcoma, definitely affects their survival adversely. The rarity of the occurrence of lymph node metastasis in primary osseous tumors, especially chondrosarcoma highlights the need for multi institutional studies to pool knowledge and evaluate the prognostic significance and etiopathogenesis of lymph node metastasis in primary bone chondrosarcoma.

TSHR rs2288496 associated with thyroid hormone and predict the occurrence of lymph node metastasis of papillary thyroid cancer.

This study aimed to evaluate the association of potential functional tagging single nucleotide polymorphisms (tagSNPs) in BRAF and TSHR with papillary thyroid cancer (PTC). Two tagSNPs (rs6464149 and rs7810757) in BRAF and six tagSNPs (rs17630128, rs2075179, rs7144481, rs2371462, rs2268477, and rs2288496) in TSHR were genotyped in 300 cases of PTC and 252 healthy controls. There was no difference in the genotype frequencies of BRAF and TSHR between PTC patients and control subjects, suggesting no contribution of BRAF or TSHR polymorphisms to the susceptibility to PTC. We observed that a tagSNP located in the 3' untranslated region of TSHR, rs2288496, could affect the incidence of lymph node metastasis (LNM). The variant TC and TC + CC genotypes conferred an increased risk of LNM (for TC vs. TT: odds ratio (OR) = 2.01, 95% confidence interval (CI): 1.07-3.77; P= 0.030; for TC + CC vs. TT: OR = 1.87, 95% CI: 1.04-3.39, P= 0.038). Moreover, subjects carrying variant genotypes had higher TSH levels and lower thyroxine (T4) and Anti-TG levels compared with those in subjects carrying common genotypes. Our findings showed that PTC patients carrying the TSHR rs2288496 TC and CC variants were associated with higher TSH level and lower T4 and Anti-TG levels and were prone to developing LNM. To confirm these results, additional studies and functional experiments, especially in other ethnic populations, are needed.