VEGF-C表达与胰腺癌淋巴结转移及预后的关系

目的 观察血管内皮生长因子(VEGF)-C在胰腺癌组织内的表达情况,分析VEGF-C的表达与胰腺癌淋巴结转移和预后之间的关系。方法 取胰腺癌病例52例,其中,伴淋巴结转移组36例,无淋巴结转移组16例。应用免疫组化法和Western blot技术观察VEGF-C在胰腺癌组织内的表达。以D2-40作为淋巴管内皮特异性标记物,观察胰腺癌组织内淋巴管生成的情况。采用Kaplan-Meier法绘制生存曲线判断VEGF-C的表达对胰腺癌预后的影响。结果 Western blot和免疫组化法检测结果表明,VEGF-C主要表达于胰腺癌细胞浆内,淋巴结转移组阳性表达量明显高于无淋巴结转移组(p<0.05)。D2-40表达于胰腺癌组织内淋巴管内皮细胞,VEGF-C阳性组淋巴管数密度明显高于VEGF-C阴性组(p<0.05),表明VEGF-C的表达与胰腺癌淋巴管生成密切相关。Kaplan-Meier生存分析表明VEGF-C表达阴性患者的生存率均高于VEGF-C表达阳性患者,VEGF-C的表达影响患者的预后。结论 VEGF-C在胰腺癌的淋巴管生成和淋巴结转移过程中发挥重要作用,VEGF-C的表达是影响胰腺癌患者预后的主要因素之一。     

Protease‐activated receptor 2 signalling promotes dendritic cell antigen transport and T‐cell activation in vivo

Deficiency of protease-activated receptor-2 (PAR2) modulates inflammation in several models of inflammatory and autoimmune disease, although the underlying mechanism(s) are not understood. PAR2 is expressed on endothelial and immune cells, and is implicated in dendritic cell (DC) differentiation. We investigated in vivo the impact of PAR2 activation on DCs and T cells in PAR2 wild-type (WT) and knockout (KO) mice using a specific PAR2 agonist peptide (AP2). PAR2 activation significantly increased the frequency of mature CD11c^high DCs in draining lymph nodes 24 hr after AP2 administration. Furthermore, these DCs exhibited increased expression of major histocompatibility complex (MHC) class II and CD86. A significant increase in activated (CD44⁺ CD62⁻) CD4⁺ and CD8⁺ T-cell frequencies was also observed in draining lymph nodes 48 hr after AP2 injection. No detectable change in DC or T-cell activation profiles was observed in the spleen. The influence of PAR2 signalling on antigen transport to draining lymph nodes was assessed in the context of delayed-type hypersensitivity. PAR2 WT mice that were sensitized by skin-painting with fluorescein isothiocyanate (FITC) to induce delayed-type hypersensitivity possessed elevated proportion of FITC⁺ DCs in draining lymph nodes 24 hr after FITC painting when compared with PAR2 KO mice (0·95% versus 0·47% of total lymph node cells). Collectively, these results demonstrate that PAR2 signalling promotes DC trafficking to the lymph nodes and subsequent T-cell activation, and thus provides an explanation for the pro-inflammatory effect of PAR2 in animal models of inflammation.     

Correlation between microsatellite instability‐high phenotype and occult lymph node metastasis in gastric carcinoma

The aim of this study is to investigate the association of microsatellite instability (MSI) status with nodal status in gastric carcinoma (GC). MSI status was investigated in 623 consecutively resected GCs. To detect occult lymph node (LN) metastasis, immunohistochemistry (IHC) using antibodies against pan‐cytokeratin was performed in 391 node‐negative cases by initial histologic examination. MSI‐high (MSI‐H) phenotype was found in 68 GC cases (10.9%) and was significantly associated with increased patient age, antral location, intestinal type, absence of venous/perineural invasion, and expanding growth type (p < 0.05). When the nodal status was evaluated, the number of metastatic LNs of MSI‐H tumors tended to be lower than that of microsatellite stable/MSI‐low (MSS/L) tumors (1.49 ± 3.15 vs 4.37 ± 9.81; p = 0.052), but the MSI‐H phenotype was associated with the presence of lymphatic invasion (p = 0.036) and IHC‐positive occult LN metastasis (p = 0.007). By multivariate analysis, MSI‐H phenotype was significantly associated with IHC‐positive occult LN metastasis (Odds ratio, 2.654; p = 0.044). MSI status and occult LN metastasis were not prognostic factors by survival analysis. Our findings suggest that the relationship between MSI status and regional LN metastasis may have some clinical and biologic implications to be elucidated.     

非小细胞肺癌淋巴结转移预测模型研究

在非小细胞肺癌的治疗过程中,淋巴结转移状态是决定治疗方案的重要因素。为了辅助临床医生制定更精确的治疗方案,开发并验证了一种基于CT影像组学非小细胞肺癌淋巴结转移的预测模型。从TCIA数据库的NSCLCRadiogenomics公共数据集中选取了134例符合试验要求的患者数据,然后从每例患者的CT影像数据中提取了1 648个特征,并用特征优化方法进行特征降维和选择,然后用朴素贝叶斯、线性判别分析、支持向量机和高斯过程5种机器学习方法建立预测模型,最后使用上海市胸科医院收集的44例患者数据进行外部验证。其中,最优淋巴结转移预测模型在训练集和测试集上准确率分别为0.802和0.795,AUC值分别为0.852和0.810。试验结果表明,所提出的预测模型分类性能良好,可以辅助医生更准确地评估淋巴结转移状态,从而制定出更精准的个性化治疗方案。     

Periprostatic lymph node metastasis in prostate cancer and its clinical significance

Deng F‐M, Mendrinos S E, Das K & Melamed J
(2012) Histopathology  60, 1004–1008
Periprostatic lymph node metastasis in prostate cancer and its clinical significance Aims: To evaluate the potential of periprostatic lymph node (LN) as a staging indicator, particularly with the use of methods for enhanced detection of micrometastasis. Methods and results: We retrieved cases with periprostatic LN from radical prostatectomy specimens accrued between 1997 and 2007 at our institution. Twenty‐one (0.8%) of 2663 radical prostatectomy specimens had periprostatic LNs (total number of LNs = 22). LN size ranged from 0.8 to 4.7 mm. Most of the periprostatic LNs were located close to the posterior base. Seven (32%) of 22 LNs were involved by metastatic prostate cancer (PCa), including five detected on routine haematoxylin and ceosin slides and an additional two detected only by immunohistochemistry. Cases with periprostatic LNs had a significantly higher metastatic rate (29%; six of 21) compared to those with pelvic LNs sampled at radical prostectatomy in our institution (1.9%). When compared to cases with negative periprostatic LNs (n = 15), the tumour characteristics of cases with metastatic periprostatic LNs (n = 6) included higher tumour volume, Gleason score, stage and a greater propensity for prostate‐specific antigen (PSA) recurrence. Conclusions: Despite their infrequent identification, periprostatic LNs if detected in the radical prostatectomy specimen should be evaluated with greater scrutiny (step sections and/or immunohistochemical studies) to evaluate their prognostic potential.     

乳腺癌前哨淋巴结活检术中不同染色淋巴结与肿瘤转移的关系

目的探讨乳腺癌前哨淋巴结活检术(SLNB)中不同染色情况的淋巴结与肿瘤转移的关系。方法选择我院2014年1月至2018年1月行前哨淋巴结活检的乳腺癌患者92例,以亚甲蓝为示踪剂,根据92例乳腺癌患者SLNB中淋巴结染色情况的不同分为无染色组、完全染色组和染色不均组,病理检测3组患者淋巴结的肿瘤转移情况并作比较。结果92例乳腺癌SLNB共取得淋巴结256枚,平均每例患者2.8枚,无染色组(80枚)肿瘤转移率为13.8%,完全染色组(112枚)肿瘤转移率为43.8%,染色不均组(64枚)肿瘤转移率为62.5%,3组间肿瘤转移率差异有统计学意义(P<0.05)。结论乳腺癌SLNB中染色不均的淋巴结最易出现肿瘤转移,其次为完全染色的淋巴结,染色淋巴结附近看到的未染色淋巴结也有肿瘤转移的可能,宜一并切除送检,有利于降低假阴性率。     

超声对乳腺癌腋下淋巴结转移状态评估价值的研究进展

超声技术作为术前评估乳腺癌腋下淋巴结转移(axillary lymph node metastasis,ALNM)状态最常用的方法,可通过二维灰阶图像、血流表现、弹性成像、超声造影等手段根据淋巴结的形态、纵横比、皮质状态、淋巴门表现、血流情况等指标预测淋巴结转移与否.但超声技术受众多影响因素如腋下淋巴结的大小、位置、腋窝深度、医师经验、超声仪器分辨率不同等的限制,其检出率及准确率仍未达到令人满意的水平.因此,如何提高超声对乳腺癌ALNM的评估效能成为亟需解决的问题.     

血管内皮生长因子C和趋化因子受体CCR7的表达与膀胱癌淋巴结转移之间的关系

目的观察血管内皮生长因子(VEGF)-C和趋化因子受体CCR7在膀胱移行细胞癌组织内的表达情况,分析VEGF-C和CCR7表达与癌淋巴结转移之间的关系。方法取膀胱癌病例60例,其中,淋巴结转移组36例,无淋巴结转移组24例。应用免疫组化法和Western blot技术观察VEGF-C和CCR7在膀胱癌组织内的表达。结果 VEGF-C和CCR7主要表达于膀胱癌细胞胞浆或/和胞膜内,二者在淋巴结转移组的表达率明显高于无淋巴结转移组。VEGF-C和CCR7蛋白同时表达在淋巴结转移组和非淋巴结转移组中的表达率分别为61.1%和33.3%,VEGF-C和CCR7的表达具有显著的相关性,联合检测VEGF-C和CCR7诊断膀胱癌淋巴结转移具有较高的准确度,ROC曲线下面积达0.708。结论 VEGF-C和CCR7在促进膀胱癌淋巴结转移中可能具有一定的协同作用,二者联合检测有助于膀胱癌淋巴结转移的早期诊断     

Establishment of lymph node metastatic model for human gastric cancer in nude mice and analysis of factors associated with metastasis

The actual mechanisms responsible for lymph node metastasis in gastric cancer are still unclear. To investigate the mechanisms of lymph node metastasis in gastric cancer, we established a lymph node metastatic model for human scirrhous gastric carcinoma. Lymph node metastasis had frequently developed after orthotopic implantation of OCUM-2M LN derived from a scirrhous gastric cancer cell line, OCUM-2M, which had low capacity for lymph node metastasis. We elucidated the different characteristics including binding ability, migratory capacity and immunoresponses induced by the cell surface molecules of these two cell lines. The binding ability to Matrigel and migratory capacity of OCUM-2M LN cells were significantly greater than those of OCUM-2M cells. On flow cytometric analysis, both OCUM-2M and OCUM-2M LN cells strongly expressed HLA-I (99.5 and 97.1%) and LFA-3 (76.6 and 99.2%) in level of expression between the two cell lines, but neither cell line expressed HLA-II (0.0 and 0 .0%), B7-1 (0.0 and 0.0%) or B7-2 (0.4 and 0.3%). ICAM-1 expression in OCUM-2M LN cells was weaker (0.7%) than that in OCUM-2M cells (36.8%). Strong adhesiveness and cytotoxicity of mononuclear lymphocytes for OCUM-2M cells were observed in adhesion and cytotoxic assays, both of which were significantly decreased by the addition of anti-ICAM-1 antibodies. On the other hand, the adhesiveness and cytotoxicity of OCUM-2M LN cells were significantly less than those of OCUM-2M cells, and were not affected by the addition of anti-ICAM-1 antibodies. These findings suggest that decreased ICAM-1 expression in a new gastric cancer cell line with a high rate of lymph node metasta-sis may in turn decrease immune responses mediated through LFA-1-dependent effector cell adhesion, and that this escape from the immunosurveillance system may be one of the factors inducing lymph node metas-tasis. In conclusion, we established a gastric cancer cell line, OCUM-2M LN, with a high rate of lymph node metasta sis. An in vivo lymph node-metastatic model with this cell line should be useful for analysing the mech-anism and therapeutic approach of lymph node metastasis. © Rapid Science Ltd.     

17q allele loss is associated with lymph node metastasis in locally aggressive human colorectal cancer

A consecutive series of 87 colorectal tumours were studied for loss of a polymorphic probe on chromosome 17q and of the 64 informative cases, 13 (20 per cent) showed loss of heterozygosity (LOH). Examples of LOH were found in carcinomas of all stages and in a large non-invasive adenoma. There was no correlation between 17q LOH and patient age, sex, standard clinicopathological variables (differentiation and nature of tumour margin), DNA ploidy, or tumour site, nor was 17q LOH associated with 17p LOH defined at four loci adjacent to p53. However, comparison of Dukes' B and C carcinomas revealed that tumours which had metastasized to regional lymph nodes at the time of primary surgery were significantly more likely to have lost this 17q allele. Clinical follow-up of this cohort of patients showed no significant difference in survival between patients whose tumours had lost or retained 17q. Thus, we conclude that 17q allele loss is associated with lymph node metastasis in locally aggressive colorectal tumours but probably not with blood-borne metastasis.     

MELF invasion in endometrial cancer as a risk factor for lymph node metastasis

Pavlakis K, Messini I, Vrekoussis T, Panoskaltsis T, Chrysanthakis D, Yiannou P & Voulgaris Z
(2011) Histopathology  58 , 966–973
MELF invasion in endometrial cancer as a risk factor for lymph node metastasis Aim: To investigate whether the microcystic, elongated and fragmented (MELF) pattern of myometrial invasion encountered in certain endometrioid endometrial carcinomas can be considered as a risk factor for lymph node metastasis. Methods and results: A total of 351 cases of total abdominal hysterectomy and bilateral salpingo‐oophorectomy with/without lymphadenectomy or lymph node sampling, performed for endometrioid endometrial adenocarcinoma, were included in this study. The existence of MELF invasion, vascular invasion, fibromyxoid stromal reaction and lymph node metastasis were recorded. Immunohistochemistry for endothelial and epithelial markers was performed on selected cases. MELF invasion was identified in 20 (10.81%) and 13 cases (13.13%) treated without and with lymphadenectomy, respectively. All these cases were either well or moderately differentiated carcinomas, stages IA–II (without considering lymph node status). Positive lymph nodes were detected in seven of 13 MELF‐positive (53.84%) and six of 86 MELF‐negative cases (6.97%) This observation was statistically significant. Of the seven MELF‐positive tumours with lymph node metastasis, three cases exhibited intravascular tumour emboli while four showed a fibromyxoid stromal reaction. Conclusion: MELF pattern invasion was found to be related statistically to lymph node metastasis. Nevertheless, further studies are needed in order to evaluate the clinical significance of this observation.     

IMP3 expression in biopsy specimens of colorectal cancer predicts lymph node metastasis and TNM stage

IMP3 is associated with lymph node metastasis and TNM stage and is a good independent prognostic biomarker for colorectal cancer (CRC). However, the expression status and clinical implication of IMP3 in biopsy specimens have not yet been studied. We aim to address whether the presence of IMP3 expression in preoperative biopsies of CRC could predict lymph node metastasis and TNM stage. In this study, we examined IMP3 expression in paired biopsy and resection specimens of 71 CRC and analyzed the correlation of IMP3 expression with clinicopathological parameters. In the biopsy specimens, IMP3 positive expression was observed in 56 of 71 cases (78.9%) whereas negative expression was observed in 15 of 71 cases (21.1%). In the resection specimens, IMP3 positive expression was detected in 83.1% cases (59/71) whereas negative expression was detected in 16.9% cases (12/71). The absolute concordance rate between biopsy and resection specimens was 90.1% (64/71). The Spearman correlation test documented the existence of a strong linear correlation between the percentage of IMP3-positive cells in the biopsy and resection specimen (r = 0.629; P < 0.001). IMP3 expression in resection specimens was significantly related to histological grade (P = 0.043), T classification (P = 0.035), lymph node metastasis (P = 0.023), TNM stage (P = 0.007), tumor border (P = 0.049) and tumor budding (P = 0.012). IMP3 expression in biopsy specimens was significantly related to lymph node metastasis (P = 0.004), TNM stage (P = 0.005) and tumor budding (P = 0.001). In conclusion, IMP3 expression in biopsy specimens could be used to predict lymph node metastasis and TNM stage in CRC patients.     

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。     

HLA antigens are candidate markers for prediction of lymph node metastasis in gastric cancer

We investigated the association between human leucocyte antigen (HLA) antigens and lymph node metastasis in 724 gastric cancer patients. Among patients who had poorly differentiated adenocarcinoma with or without HLA-DR4 antigen, lymph node metastasis was detected in 80.8 and 54.9%, respectively (relative risk (RR)=3.5, P = 0.0005, corrected P = 0.0285). It was more common in patients with a family history of cancer death (RR = 7.7). Among signet ring cell carcinoma patients with or without HLA-1152 antigen, lymph node metastasis was detected in 57.7 and 19.7%, respectively (RR =5.6, P=0.0001, corrected P=0.0086). It was more common in patients who were smokers (RR = 8.3). Our findings suggest that HLA-DR4 and HLA-1152 antigens are associated with lymph node metastasis in gastric cancer.     

Tumour stroma‐derived lipocalin‐2 promotes breast cancer metastasis

Tumour cell‐secreted factors skew infiltrating immune cells towards a tumour‐supporting phenotype, expressing pro‐tumourigenic mediators. However, the influence of lipocalin‐2 (Lcn2) on the metastatic cascade in the tumour micro‐environment is still not clearly defined. Here, we explored the role of stroma‐derived, especially macrophage‐released, Lcn2 in breast cancer progression. Knockdown studies and neutralizing antibody approaches showed that Lcn2 contributes to the early events of metastasis in vitro. The release of Lcn2 from macrophages induced an epithelial–mesenchymal transition programme in MCF‐7 breast cancer cells and enhanced local migration as well as invasion into the extracellular matrix, using a three‐dimensioanl (3D) spheroid model. Moreover, a global Lcn2 deficiency attenuated breast cancer metastasis in both the MMTV–PyMT breast cancer model and a xenograft model inoculating MCF‐7 cells pretreated with supernatants from wild‐type and Lcn2‐knockdown macrophages. To dissect the role of stroma‐derived Lcn2, we employed an orthotopic mammary tumour mouse model. Implantation of wild‐type PyMT tumour cells into Lcn2‐deficient mice left primary mammary tumour formation unaltered, but specifically reduced tumour cell dissemination into the lung. We conclude that stroma‐secreted Lcn2 promotes metastasis in vitro and in vivo, thereby contributing to tumour progression. Our study highlights the tumourigenic potential of stroma‐released Lcn2 and suggests Lcn2 as a putative therapeutic target. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

中性粒细胞—淋巴细胞比预测早期胃癌淋巴结转移的临床价值

目的分析中性粒细胞—淋巴细胞比(NLR)预测早期胃癌(EGC)淋巴结转移的临床价值,以期为EGC治疗方案的制订提供参考。方法回顾性分析在我院行胃癌根治术并经术后病理确诊为EGC的134例患者的临床资料,根据淋巴结是否转移分为阳性组和阴性组。收集EGC患者术前1周血液学指标并计算血小板—淋巴细胞比(PLR)和NLR;收集患者基本信息及术后病理信息,行单因素和多因素Logistic回归分析;通过受试者工作特征(ROC)曲线分析NLR预测EGC伴淋巴结转移阳性的诊断价值;分析术前NLR与患者一般资料及临床病理之间的相关性;Pearson相关性检验分析NLR与肿瘤大小的相关性;Kaplan-Meier(K-M)曲线及Log-rankχ2检验比较高NLR组和低NLR组患者术后生存状况。结果单因素分析结果显示,浸润深度、分化程度、肿瘤大小、PLR、NLR与淋巴结转移相关(P<0.05)。多因素Logistic回归分析结果显示,肿瘤大小≥2cm、浸润深度为黏膜下层、分化程度为低分化、NLR≥1.965是淋巴结转移的独立危险因素(P<0.05)。根据ROC曲线,NLR截断值为2.295,术前NLR预测淋巴结转移的灵敏性和特异性分别为82.6%和77.5%。根据截断值将所有患者分为低NLR组(NLR<2.295)90例和高NLR组(NLR≥2.295)44例,2组患者一般资料及临床病理相关因素分析结果显示,术前NLR与年龄、肿瘤大小、肿瘤大体类型显著相关(P<0.05)。术前NLR与肿瘤大小呈正相关(r=0.645,P<0.001)。术前高NLR组患者术后5年生存率明显低于低NLR组患者(P<0.05)。结论术前NLR对EGC患者发生淋巴结转移具有较高的预测价值,且对EGC患者预后的评估具有一定的临床参考价值。