Loss of membranous E-cadherin expression in pancreatic cancer: Correlation with lymph node metastasis,high grade,and advanced stage

Epithelial cadherin (E-cadherin) is a Ca²⁺-dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss of downregulation is associated with an invasive and poorly differentiated phenotype in colon and other tumours. We have used an avidin-biotin immunoperoxidase technique to localize E-cadherin in microwave-treated, paraffin-embedded sections from 36 patients with pancreatic adenocarcinomas. E-cadherin was expressed by normal ductal and acinar cells with typical membranous staining at the intercellular junctions. Loss of normal surface E-cadherin expression was found in 19/36 (53 per cent) tumours compared to the adjacent normal ductal cells. Abnormal E-cadherin expression was found more frequently in poorly differentiated (grade III) (6/7, 86 per cent) than in well-differentiated tumours (grade I) (4/14, 28 per cent) (P=0·012). Membranous E-cadherin expression was also lost more frequently in primary tumours with lymph node (stage III) (14/23, 61 per cent) and distant metastasis (stage IV) (2/2, 100 per cent) compared with 3/11 (27 per cent) lymph node-negative tumours (stage I) (P=0·043). In conclusions, our data indicate that loss of membranous E-cadherin expression is associated with high grade and advanced stage in pancreatic cancer.     

Increased expression of IRS-1 is associated with lymph node metastasis in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China, which is with characteristics of early cervical lymph node metastasis and high incidence rate of distant metastasis. Insulin receptor substrate 1 (IRS-1) is a signaling adapter protein that is encoded by the IRS-1 gene in humans, plays an important role in the development, progression, invasion and metastasis of tumors. The aim of the present study was to investigate the association between the expression of IRS-1 protein and clinicopathological characteristics in NPC by immunohistochemistry. The results showed that the expression level of IRS-1 was significant higher in NPC than that in the control nasopharyngeal epithelia (P = 0.042). The positive percentage of IRS-1 expression in NPC with lymph node metastasis was also significantly higher than those without lymph node metastasis (P = 0.008). Positive expression of IRS-1 was proved to be the independent predicted factor for lymph node metastasis of NPC (P = 0.025) regardless of age, gender, histological type and clinical stages by multivariate logistic regression analysis. In addition, results showed higher sensitivity and agreement rate of IRS-1 for predicting lymph node metastasis of NPC patients. Taken together, high expression of IRS-1 might be closely correlated with lymph node metastasis in NPC and positive expression of IRS-1 could be used as an independent biomarker for predicting lymph node metastasis of NPC.     

基于机器学习的鼻咽癌转移淋巴结鉴别模型

目的:研究使用机器学习与影像组学建立用于鼻咽癌CT图像中鉴别转移淋巴结的模型。方法:选择50例鼻咽癌患者初诊CT平扫及静脉灌注增强图像及18F-FGD-PET图像,患者均经病理及PET检查证实为鼻咽癌伴局部淋巴结转移。手动勾画患者CT图像中体积＞1 cm3的淋巴结,由18F-FGD-PET图像中对应区域SUVmax＞2.5及现行影像学标准作为转移与否的分类标准。研究中共获得143枚淋巴结,其中转移淋巴结103枚。使用机器学习方法对上述分类结果进行训练,其中列入训练组淋巴结100枚,验证组43枚,分组方式为随机分组以避免特定的分组方式造成的系统误差。结果:机器学习过程中获得由淋巴结体积、最大横截面短轴及数个影像组学特征构建模型,模型对转移淋巴结的鉴别准确率可达86%。特征选择结果得出:最大横截面直径、平均宽度、灰度强度能量、像素数量、频度、形态密实度等可作为诊断转移淋巴结的重要特征。结论:研究中建立的鉴别模型可在CT图像中实现辅助诊断转移淋巴结,为影像检查中快速判定鼻咽癌患者淋巴结是否转移提供一种新思路,有利于个体化放疗中靶区的精准勾画。     

Tenascin-C expression in Merkel cell carcinoma lymph node metastasis

Expression of tenascin-C (Tn-C) has been shown to correlate with invasion and metastasis in Merkel cell carcinoma (MCC). Cytokeratin-20 (CK-20) is used in differential diagnostics of the primary tumour. The aim of this study was to demonstrate the expression of Tn-C in MCC lymph node metastases. Immunohistochemical staining was performed for five metastatic lymph nodes using a monoclonal antibody against Tn-C and CK-20. All five metastatic lymph nodes expressed Tn-C. The expression concentrated around the vascular structures, invasion borders and fibrotic septae. One of the metastatic lymph nodes was strongly positive for CK-20 while the others showed a focal or negative pattern. The normal lymphoid tissue was negative for Tn-C. Tn-C detected metastatic MCC tissue within the lymph nodes undisputedly. There was a clear distinction between the metastatic and normal lymphatic tissue. Furthermore, invasion to the surrounding tissue was easily demonstrated. Contrary to previous studies, CK-20 expression seemed to fluctuate.     

Gastric carcinoma with invasive micropapillary pattern and its association with lymph node metastasis

Ushiku T, Matsusaka K, Iwasaki Y, Tateishi Y, Funata N, Seto Y & Fukayama M
(2011) Histopathology  59 , 1081–1089
Gastric carcinoma with invasive micropapillary pattern and its association with lymph node metastasis Aims: This study aimed to characterize the clinicopathological features of invasive micropapillary carcinoma (IMPC) of the stomach. Methods and results: Seventeen cases of gastric IMPC were identified from histological reviews of 1178 consecutive cases. IMPC components occupied 10–90% of the entire tumours. Fifteen tumours showed invasion into the muscularis propria or deeper, whereas two tumours were limited to the submucosa. All 17 cases were associated with tubular or papillary adenocarcinoma. Lymphatic and venous invasion were identified more frequently in cases with IMPC components than in those without (P = 0.0023 and P = 0.0009, respectively). Nodal metastases were identified in 14 of 17 (82%) cases with IMPC components, whereas they were detected in 540 of 1161 (47%) cases with no IMPC components (P = 0.0053). Multivariate analysis demonstrated that the presence of IMPC was an independent predictor of nodal metastasis. Conclusions: Conservative treatments, such as endoscopic resection, should not be used for gastric carcinoma with IMPC components, as these cases are associated with a high propensity for lymphovascular invasion and nodal metastasis.     

Lower and reduced expression of EphA4 is associated with advanced TNM stage,lymph node metastasis,and poor survival in breast carcinoma

The expression of EphA4 has been well documented in the development of nerve and in certain types of human cancer. Few studies of EphA4, however, have focused on breast carcinoma. In this study, a set of breast carcinomas was subjected to immunohistochemical staining. In normal luminal cells, EphA4 was weakly detected in 11 (14.3 %), moderately detected in 15 (19.5 %) and highly detected in 51 out of 77 (66.2 %) samples, while in breast carcinoma cells, EphA4 was weakly detected in 42 (54.5 %), moderately detected in 19 (24.7 %) and highly detected in 16 out of 77 (20.8 %) samples (P < 0.001). The expression of EphA4 protein was significantly reduced in 68.8 % of breast carcinoma samples comparing with normal cells. The expression of EphA4 was significantly associated with tumor grade (P = 0.003), TNM stage (P = 0.034), lymph node metastasis (P = 0.034) and Ki‐67 (P < 0.001). No significant relationship was found between the expression of EphA4 and age, molecular subtypes, and HER2 status. Survival analysis showed that significant association of low expression of EphA4 in tumor cells with short overall survival (P = 0.048) and disease‐free survival (P = 0.051). Our data show that EphA4 was reduced in breast carcinoma, which is associated with high grade, advanced TNM stage, lymph node metastasis, and poor outcome of patients.     

Decreased expression of E-cadherin and Yamamoto-Kohama's mode of invasion highly correlates with lymph node metastasis in esophageal squamous cell carcinoma.

OBJECTIVES: A reduction in cell-cell adhesion in cancer cells is an essential step in the progression from localized malignancy to metastatic disease. E-Cadherin is an important component of cell-cell adhesion molecules and may be a crucial determinant of tumor invasion and metastasis. E-Cadherin expression is reported to be correlated with lymph node metastasis in esophageal squamous cell carcinoma (SCC). The objective of this experiment is to examine the factors that are associated with invasion and metastasis of esophageal SCC. METHODS: Forty-six cases of esophageal SCC were examined by immunohistochemical staining for E-cadherin. The relationship between E-cadherin-staining patterns, conventional clinicopathological parameters and Yamamoto-Kohama's (Y-K's) mode of invasion were examined. RESULTS: The expression of E-cadherin on the cell membrane was reduced or lost in some of the esophageal SCC. Lymph node metastasis was highly correlated with the expression pattern of E-cadherin (p = 0.0002) and also highly correlated with Y-K's mode of invasion (p = 0.0078). However, lymph node metastasis was not correlated with any conventional clinicopathological parameters for invasion. CONCLUSIONS: These results indicate that E-cadherin plays a crucial role in invasion and metastasis in esophageal SCC, and that Y-K's mode of invasion highly reflects the invasiveness and metastatic potentials of esophageal SCC cells. Therefore, examination of the expression of E-cadherin and Y-K's mode of invasion would be helpful in predicting lymph node metastasis in esophageal SCC.     

鼻咽癌颈部淋巴结转移MR多b值DWI成像研究分析

目的：研究在鼻咽癌(nasopharyngeal carcinoma,NPC)颈部淋巴结转移的评价中1.5T MR多b值扩散加权成像(diffusion weighted imaging,DWI)的应用价值。方法：对良性淋巴结增大病人15例及鼻咽癌病人37例进行常规MR及多b值DWI检查,对不同b值的DWI图像质量进行比较。对不同b值下良、恶性淋巴结ADC值的ROC曲线进行记录。结果：b=800 s/mm2时鼻咽部变形小,图像背景抑制充分,伪影少,周围软组织与病灶具有较好的对比度,小淋巴结显示清楚;鼻咽癌、良性淋巴结及颈部转移性淋巴结的ADC值随着b值增大均呈下降趋势,8种b值下转移性淋巴结与鼻咽癌原发灶向比较,ADC值差异无统计学差异(P>0.05)。而良性淋巴结与转移性淋巴结相比较,ADC值差异均有统计学差异(P<0.05);b=800 s/mm2时对良恶性淋巴结的鉴定效果最好,灵敏度为100%,特异度为83.2%。结论：1.5T MR扩散加权成像(DWI)技术能有效鉴别淋巴结性质,b值取800 s/mm2时,DWI图像具有较好的质量,且对良恶性淋巴结的鉴定诊断效果最好,可在临床鼻咽癌颈部淋巴结转移的诊断中推广应用。     

E-cadherin与乳腺癌分化程度及其淋巴结转移的关系研究

目的 探讨E-cadherin基因表达在乳腺癌侵袭和转移中的作用。方法 采用原位杂交技术检测30例正常乳腺组织和48例乳腺癌原发肿瘤及其淋巴结转移灶中E-cadherinmRNA表达情况。结果 乳腺癌原发肿瘤组织和淋巴结转移灶中，E-cadherin mRNA阴性表达率（分别为31．3％，46．7％）与正常乳腺组织之间的差异非常显著（P＜0．001）。E-cadherin mRNA表达强度在乳腺癌Ⅰ-Ⅲ级之间及有无淋巴结转移的原发肿瘤之间有显著性差异（P＜0．05）。结论 肿瘤抑制基因E-cadherin是一种有价值的反映乳腺癌恶性程度和预测淋巴结转移的指标。     

Serum proteome analysis for profiling protein markers associated with carcinogenesis and lymph node metastasis in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC), one of the most common cancers in population with Chinese or Asian progeny, poses a serious health problem for southern China. It is unfortunate that most NPC victims have had lymph node metastasis (LNM) when first diagnosed. We believe that the 2D based serum proteome analysis can be useful in discovering new biomarkers that may aid in the diagnosis and therapy of NPC patients. To filter the tumor specific antigen markers of NPC, sera from 42 healthy volunteers, 27 non-LNM NPC patients and 37 LNM NPC patients were selected for screening study using 2D combined with MS. Pretreatment strategy, including sonication, albumin and immunoglobulin G (IgG) depletion, was adopted for screening differentially expressed proteins of low abundance in serum. By 2D image analysis and MALDI-TOF-MS identification, twenty-three protein spots were differentially expressed. Three of them were further validated in the sera using enzyme-linked immunosorbent assay (ELISA). Our research demonstrates that HSP70, sICAM-1 and SAA, confirmed with ELISA at sera and immunohistochemistry, are potential NPC metastasis-specific serum biomarkers which may be of great underlying significance in clinical detection and management of NPC.     

E-cadherin, beta-catenin, invasion and lymph node metastases in canine malignant mammary tumours

Recent studies of canine malignant mammary tumours suggest that reduction of E-cadherin and/or beta-catenin correlates with invasive behaviour and lymph node metastasis. The aims of this study were to examine the interrelationships between the expression of E-cadherin and beta-catenin, and the relationship between the expression of E-cadherin and/or beta-catenin and the mode of growth and metastatic capacity of canine malignant mammary tumours. 90 spontaneous malignant tumours and local and regional lymph nodes were studied. A significant relationship was evidenced between membranous expression of E-cadherin and beta-catenin (p=0.0027), but not between E-cadherin and cytoplasmic beta-catenin. Only E-cadherin as a separate factor was significantly related to tumour invasion (p=0.0072) and lymph node metastasis (p=0.0001). Neither membranous nor cytoplasmic beta-catenin expression was significantly related to either of these phenomena.     

Overexpression of CD9 correlates with tumor stage and lymph node metastasis in esophageal squamous cell carcinoma

Objective: Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer deaths worldwide. CD9 has been reported to play a critical role in cell motility, growth and metastasis of multiple cancers. The present study investigated the clinicopathological features of CD9, and its biological characteristics in ESCC. Methods: Fifteen normal esophageal tissue specimens, fifty-three ESCC adjacent tissues and one hundred and four ESCC tissues were included in this study. Using immunohistochemistry (IHC), the expression levels of CD9 were evaluated among different samples. And its clinicopathological parameters and its prognostic factors were analyzed. Western blotting was used to measure CD9 expression and colony formation was performed to determine the effect of CD9 on cell growth in ESCC TE-1 cells. Results: Compared with normal esophageal tissues and tumor adjacent tissues, CD9 expression level is significantly higher in ESCC tissues. CD9 expression correlated with tumor stage (P = 0.022) and lymph node metastasis (P = 0.019) in ESCC patients. Furthermore, the small interfering RNA-mediated silencing of CD9 expression in TE-1 cells resulted in increased proliferation as evidenced by increased colony number and colony size. Conclusion: CD9 expression is upregulated in ESCC tissues and its expression is correlated with tumor stage and lymph node metastasis in ESCC patients. CD9 suppresses the proliferation of TE-1 cells. CD9 may present a potential in tumor progression in ESCC.     

SDF-1和VEGF-C在结肠癌中的表达及与淋巴结转移的关系

目的探讨结肠癌组织中基质细胞衍生因子SDF-1、血管内皮生长因子-C（VEGF-C）表达的相互关系及其在淋巴结转移过程中的作用和可能机制。方法应用免疫组化法检测70例结肠癌组织和12例癌旁组织中SDF-1及VEGF-C的表达水平。结果结肠癌组织中SDF-1、VEGF-C阳性表达率分别为71．4％、64．3％,显著高于癌旁非癌组织的16．7％和8．3％（P〈0．01）。SDF-1、VEGF-C的表达与结肠癌的浸润深度、淋巴结转移及TNM分期有关（P〈0、01或P〈0．05）,与结肠癌的分化程度、远处转移无关（P〉0．05）。SDF-1、VEGF-C之间表达呈正相关（r=0．608,P〈0．05）。结论结肠癌组织中SDF-1、VEGF-C表达均显著增高,两者在结肠癌淋巴结转移中可能具有协同效应,共同促进结肠癌的淋巴结转移。     

胃癌中微小干扰RNA-20a表达与TNM分期和淋巴结转移的关系

目的 分析微小干扰RNA(miRNA)-20a在胃癌中表达与胃癌TNM分期和淋巴结转移的关系.方法 选取本院普外科于2011年10月至2013年10月收治的145例胃癌患者作为临床观察对象,利用PCR检测并对比这些患者胃癌组织与癌周正常组织的miRNA-20a表达水平,分析其与TNM分期和淋巴结转移的关系.结果 胃癌组织中miRNA-20a的表达水平明显高于癌周正常组织(2.18±0.38比0.65±0.13,P＜0.05).高TNM分期(Ⅲ+Ⅳ期)组较低TNM分期(Ⅰ+Ⅱ期)组胃癌组织中miRNA-20a的表达上调(2.84±0.45比1.37±0.24,P＜0.05).淋巴结转移阳性的患者胃癌组织中miRNA-20a的表达要明显高于淋巴结转移阴性的患者(2.65±0.63比1.88±0.54,P＜0.05).结论 胃癌组织中miRNA-20a的表达升高,其表达与胃癌的TNM分期与淋巴结转移有关.     

Increased expression of integrin beta-4 in papillary thyroid carcinoma with gross lymph node metastasis

Although the prognosis is generally good for patients with papillary thyroid carcinoma, gross nodal metastasis of carcinoma has a poor prognosis. It is necessary to clarify how carcinoma progresses to gross nodal metastasis in order to establish a cure. The adhesion molecule integrin beta-4 is considered to be related to cell migration and metastasis in many carcinomas. In the present study, we examined integrin beta-4 expression in 65 cases of human papillary thyroid carcinoma using immunohistochemical methods. Expression of integrin beta-4 was found in all papillary carcinomas, but in few normal thyrocytes. Interestingly, integrin beta-4 expression in the carcinomas with gross (> or =3 cm) lymph node metastasis was significantly higher than that in carcinomas with small (<3 cm) or no lymph node metastasis. These results suggest that integrin beta-4 expression in thyroid carcinoma may play a role in the development of gross lymph node metastasis of papillary carcinomas.     

乳腺癌中Syk、VEGF-C表达与淋巴结转移的关系

目的研究乳腺癌组织中Syk、VEGF-C的表达与淋巴结转移的关系。方法分别采用免疫组织化学EnVision两步法及SP法检测55例乳腺癌组织中Syk、NFκB(p65)及VEGF-C的表达情况。结果55例乳腺癌组织中,Syk、VEGF-C及p65阳性率分别为50.9%,56.4%,81.8%。Syk在淋巴结转移组的表达低于无淋巴结转移组(P0.05);VEGF-C在淋巴结转移组的表达高于无淋巴结转移组(P0.05);p65在两组之间的表达差异无显著性(P0.75),p65胞核移位率在淋巴结转移组高于无淋巴结转移组(P0.025)。随着Syk表达增强VEGF-C的表达减弱,二者呈负相关(r=-0.620,P=0.000);p65胞核移位与Syk的表达强度降低有关(r=0.448,P=0.002),而与VEGF-C的表达强度增高有关(r=0.310,P=0.036)。结论乳腺癌中,Syk可能通过抑制NFκB的活性而下调VEGF-C的表达,从而抑制乳腺癌的淋巴结转移。