Identification of Biological Properties of Intralymphatic Tumor Related to the Development of Lymph Node Metastasis in Lung Adenocarcinoma

Background

Intralymphatic tumors in the extratumoral area are considered to represent the preceding phase of lymph node metastasis. The aim of this study was to clarify the biological properties of intralymphatic tumors susceptible to the development of lymph node metastasis, with special reference to the expression of cancer initiating/stem cell (CIC/CSC) related markers in cancer cells and the number of infiltrating stromal cells.

Material and Methods

Primary lung adenocarcinomas with lymphatic permeation in the extratumoral area were retrospectively examined (n = 107). We examined the expression levels of CIC/CSC related markers including ALDH1, OCT4, NANOG, SOX2 and Caveolin-1 in the intralymphatic cancer cells to evaluate their relationship to lymph node metastasis. Moreover, the number of infiltrating stromal cells expressing CD34, α-smooth muscle actin, and CD204 were also evaluated.

Results

Among the intralymphatic tissues, low ALDH1 expression in cancer cells, high SOX2 expression in cancer cells, and a high number of CD204(+) macrophages were independent predictive factors for lymph node metastasis (P = 0.004, P = 0.008, and P = 0.028, respectively). Among these factors, only low ALDH1 expression in cancer cells was significantly correlated with the farther spreading of lymph node metastasis (mediastinal lymph node, pathological N2) (P = 0.046) and the metastatic lymph node ratio (metastatic/resected) (P = 0.028). On the other hand, in the primary tumors, ALDH1 expression in the cancer cells was not associated with lymph node metastasis. Intralymphatic cancer cells expressing low ALDH1 levels exhibited lower E-cadherin expression levels than cancer cells with high levels of ALDH1 expression (P = 0.015).

Conclusions

Intralymphatic cancer cells expressing low levels of ALDH1 and infiltrating macrophages expressing CD204 have a critical impact on lymph node metastasis. Our study also highlighted the significance of evaluating the biological properties of intralymphatic tumors for tumor metastasis.     

经支气管针吸活检术对肺癌伴纵隔淋巴结转移的临床诊断价值

目的评价经支气管针吸活检术（transbronchial needle aspiration,TBNA）对伴有纵膈淋巴结转移的肺癌临床诊断价值。方法对肺部CT检查疑诊为伴有淋巴结转移的肺癌53例患者,在常规支气管镜行刷检和活检后,对转移肿大的纵隔淋巴结行经支气管针吸活检术（TBNA）,对获取的标本实行相应的病理学检查。结果 53例患者经三种结合的纤支镜检查明确诊断46例,其中组织活检、刷检和TBNA的阳性率分别是64.2%、60.4%、58.5%,常规组织刷检及活检的阳性率为69.8%,结合TBNA术的阳性率增加至86.8%。参检者术中及术后均未发现严重的并发症。结论 TBNA术对于伴有纵膈淋巴结转移的肺癌患者具有较高的临床诊断价值。     

Lymph Node Metastases and Prognosis in Left Upper Division Non-Small Cell Lung Cancers: The Impact of Interlobar Lymph Node Metastasis

Background

Left upper division segmentectomy is one of the major pulmonary procedures; however, it is sometimes difficult to completely dissect interlobar lymph nodes. We attempted to clarify the prognostic importance of hilar and mediastinal nodes, especially of interlobar lymph nodes, in patients with primary non-small cell lung cancer (NSCLC) located in the left upper division.

Methods

We retrospectively studied patients with primary left upper lobe NSCLC undergoing surgical pulmonary resection (at least lobectomy) with radical lymphadenectomy. The representative evaluation of therapeutic value from the lymph node dissection was determined using Sasako’s method. This analysis was calculated by multiplying the frequency of metastasis to the station and the 5-year survival rate of the patients with metastasis to the station.

Results

We enrolled 417 patients (237 men, 180 women). Tumors were located in the lingular lobe and at the upper division of left upper lobe in 69 and 348 patients, respectively. The pathological nodal statuses were pN0 in 263 patients, pN1 in 70 patients, and pN2 in 84 patients. Lymph nodes #11 and #7 were significantly correlated with differences in node involvement in patients with left upper lobe NSCLC. Among those with left upper division NSCLC, the 5-year overall survival in pN1 was 31.5% for #10, 39.3% for #11, and 50.4% for #12U. The involvement of node #11 was 1.89-fold higher in the anterior segment than that in the apicoposterior segment. The therapeutic index of estimated benefit from lymph node dissection for #11 was 3.38, #4L was 1.93, and the aortopulmonary window was 4.86 in primary left upper division NSCLC.

Conclusions

Interlobar node involvement is not rare in left upper division NSCLC, occurring in >20% cases. Furthermore, dissection of interlobar nodes was found to be beneficial in patients with left upper division NSCLC.     

Increased Expression of Flotillin-2 Protein as a Novel Biomarker for 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. Flotillin-2 (Flot-2) is not only an important component of cellular membrane, but also involves in various cellular processes such as membrane trafficking, T cell and B cell activation, regulation of several signaling pathways associated with cell growth and malignant transformation, keeping structure and junction of epidermal cells and formation of filopodia. Although such molecular effects of Flot-2 have been reported, whether the expression of Flot-2 protein is associated with clinicopathologic implication for NPC has not been reported. The purpose of this research is to investigate the expression of Flot-2 protein in NPC and control nasopharyngeal epithelial tissues by immunohistochemistry and elucidate the association between the expression of Flot-2 protein and clinicopathological characteristics of NPC. The results showed that the positive percentage of Flot-2 expression in the NPC, nasopharyngeal epithelia with atypical hyperplasia and in the control nasopharyngeal mucosa epithelia was 88.8% (119/134), 76.9% (10/13) and 5.7% (5/88), respectively. There was significantly higher expression of Flot-2 protein in NPC and nasopharyngeal epithelia with atypical hyperplasia compared to the control nasopharyngeal mucosa epithelia (P<0.001, respectively). The positive percentage of Flot-2 protein expression in NPC patients with lymph node metastasis was significantly higher than those without lymph node metastasis. Increasing of Flot-2 expression was obviously correlated with clinical stages of NPC patients. The expression of Flot-2 was proved to be the independent predicted factor for lymph node metastasis by multivariate analysis. The sensitivity of Flot-2 for predicting lymph node metastasis of NPC patients was 93%. Taken together, our results suggest that the increased expression of Flot-2 protein is a novel higher sensitivity biomarker that can predict lymph node metastases in NPC.     

Lymph Node Ratio for Postoperative Staging of Laryngeal Squamous Cell Carcinoma with Lymph Node Metastasis

Background

Lymph node metastasis has a significant impact on laryngeal cancer prognosis. The role of lymph node ratio (LNR, ratio of metastatic to examined nodes) in the staging of laryngeal cancer was not reported.

Patients and Methods

Records of laryngeal cancer patients with lymph node involvement from Surveillance, Epidemiology, and End Results database (SEER, training set, N = 1963) and Fudan University Shanghai Cancer Center (FDSCC, validating set, N = 27) were analyzed for the prognostic value of LNR. Kaplan–Meier survival estimates, the Log-rank χ² test and Cox proportional hazards model were used for univariate and multivariate analysis. Optimal LNR cutoff points were identified by X-tile.

Results

Optimal LNR cutoff points classified patients into three risk groups R1 (≤0.09), R2 (0.09–0.20) and R3 (>0.20), corresponding to 5-year cause-specific survival and overall survival in SEER patients of 55.1%, 40.2%, 28.8% and 43.1%, 31.5%, 21.8%, 2-year disease free survival and disease specific survival in FDSCC patients of 74.1%, 62.5%, 50.0%, and 67.7%, 43.2%, 25.0%, respectively. R3 stratified more high risk patients than N3 with the same survival rate, and R classification clearly separated N2 patients to 3 risk groups and N1 patients to 2 risk groups (R1–2 and R3).

Conclusions

R classification is a significant prognostic factor of laryngeal cancer and should be used as a complementary staging system of N classification.     

直肠癌的淋巴结转移的危险因素

目的:本研究主要目的为确定直肠癌的淋巴结转移的危险因素。方法:通过对1250例于2004年-2008年行直肠癌根治性切除的患者进行单因素和多因素分析,以确定淋巴结转移相关的危险因素,同时对PT分期和肿瘤大小之间的关系进行了相关性分析。结果:直肠癌患者淋巴结转移发生率为41%。在单因素分析中,患者年龄(P=0.008)、肿瘤大小(P=0.003)、PT分期(P<0.0019)以及分化程度(P<0.001)和淋巴结转移相关。在多因素分析中,年龄(P=0.017,OR=0.988,95%可信区间:0.978-0.998)、PT分期(P<0.001,OR=1.952,95%可信区间:1.656-2.302)和分化程度(P<0.001,OR=3.697,95%可信区间:2.112-6.472)是淋巴结转移的独立因素。结论:在直肠癌相关分析中,肿瘤的大小和PT分期呈正相关。年龄、PT分期和肿瘤分化程度是淋巴结转移的独立因素。在直肠癌中,肿瘤的大小和PT分期呈正相关。     

Reduced Expression of ZDHHC2 Is Associated with Lymph Node Metastasis and Poor Prognosis in Gastric Adenocarcinoma

Background

Zinc finger, DHHC-type containing 2 (ZDHHC2), originally named as reduced expression associated with metastasis protein (REAM), has been proposed as a putative tumor/metastasis suppressor gene and is often aberrantly decreased in human cancers. However ZDHHC2 expression pattern and its clinical significance have not yet been investigated in gastric adenocarcinoma.

Methodology/Principal Findings

Quantitative Real-Time PCR (qRT-PCR) and immunostaining were performed to detect ZDHHC2 expression in gastric adenocarcinoma, and then the correlation between ZDHHC2 expression and clinicpathologic parameters, and patient survival was analyzed. Compared to the adjacent normal tissues, ZDHHC2 expression was significantly reduced in gastric tumor tissues as shown by qRT-PCR and immunostaining. Low expression of ZDHHC2 was observed in 44.7% (211/472) of gastric adenocarcinoma patients, and was associated significantly with lymph node metastasis (p<0.001) and histological grade (p<0.001). Multivariate Cox regression analysis indicated that ZDHHC2 expression had a significant, independent predictive value for survival of gastric cancer patients (HR = 0.627, p = 0.001).

Conclusions/Significance

Our data suggest that reduced ZDHHC2 expression is associated with lymph node metastasis and independently predicts an unfavorable prognosis in gastric adenocarcinoma patients.     

卵巢癌中结缔组织生长因子的表达及其临床病理意义

目的:探讨卵巢癌中结缔组织生长因子(CTGF)的表达及其与卵巢癌临床病理特征的关系。方法:采用免疫组化法检测116例卵巢癌和25例正常卵巢组织中CTGF表达,并分析其与卵巢癌临床病理参数的关系。结果:正常卵巢组织及卵巢癌中CTGF的阳性表达率分别96%(24/25)、65%(75/116),卵巢癌中CTGF的阳性表达率显著低于正常卵巢组织(P0.05)。CTGF的表达降低与卵巢癌患者的淋巴结转移、腹膜内转移及对化疗的敏感性显著相关(P0.05);进一步的多因素Logistic回归分析显示CTGF的表达与卵巢癌腹膜转移(P=0.006,OR=4.185,95%CI=1.447-11.352)和淋巴结转移(P0.001,OR=6.336,95%CI=2.563-15.972)均显著相关。结论:卵巢癌中CTGF的表达缺失,是卵巢癌腹膜转移和淋巴结转移的独立影响因素,可能作为预测卵巢癌转移的参考指标。     

SDF-1/CXCR4及VEGF-C 在喉癌淋巴结转移中的作用机制

目的:探讨SDF-1/CXCR4及VEGF-C在喉癌淋巴结转移中的作用机制。方法:随机选取2012年8月至2015年8月我院收治的90例喉癌患者,将这些患者作为研究组,另选取20例具有相应正常粘膜组织的患者为对照组,运用免疫组化SP法对CXCR4及VEGF-C及SDF-1进行检测,分析SDF-1/CXCR4及VEGF-C在喉癌淋巴结组织中的表达及其与临床病理特征的关系。结果:喉癌组织中CXCR4、VEGF-C、SDF-1的阳性表达率均显著高于正常组织(P0.05);Ⅲ+Ⅳ患者CXCR4、VEGF-C、SDF-1的阳性表达率均显著高于Ⅰ+Ⅱ患者(P0.05);低分化患者CXCR4、VEGF-C的阳性表达率均显著高于高中分化患者(P0.05),但SDF-1阳性表达率之间比较,差异均不具有统计学意义(P0.05);淋巴结转移患者CXCR4、VEGF-C、SDF-1的阳性表达率均显著高于未发生淋巴结转移的患者,差异具有统计学意义(P0.05);不同年龄、病变部位患者CXCR4、VEGF-C、SDF-1阳性表达率之间比较,差异均不具有统计学意义(P0.05);喉癌组织中CXCR4及VEGF-C阳性表达均呈显著的正相关关系(P0.05);阴性表达也均呈显著的正相关关系(P0.05)。结论:SDF-1/CXCR4及VEGF-C在喉癌淋巴结转移中高表达,可能共同促进喉癌淋巴结转移。     

Follistatin Is a Novel Biomarker for Lung Adenocarcinoma in Humans

Background

Follistatin (FST), a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.

Methods and Results

The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80), which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40) using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.

Conclusions

These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.     

VEGF—C、CD24在肺癌组织的表达及其与淋巴结转移及预后的关系

目的：探讨内皮生长因子一C（vascularendothelialgrowthfactor-C,VEGF-C）、黏附分子CD24在肺癌组织中的表达及其临床意义。方法：采用RT-PCR和免疫组化方法检测138例原发性肺癌患者肿瘤组织及癌旁组织中VEGF-C、CD24的表达水平。结果：肺癌组织中VEGF-C、CD24mRNA及蛋白的表达均高于癌旁组织（P〈0．05）,两者在肺癌组织中的表达明显正相关（P〈O．05）;有淋巴结转移组中vEGF-C、CD24mRNA及蛋白的阳性表达量均高于无淋巴结转移组（P〈0．05）;VEGF—C、CD24表达与淋巴结转移、肿瘤TNM分期等临床病理特征间有明显相关性（P〈0．05）;VEGF—C、CD24蛋白表达与IIIA期患者的短期预后有关,两者的mRNA水平与无病生存时间呈负相关。结论：VEGF-C、CD24在肺癌组织中均异常表达,可作为肺癌诊断的辅助标志物。     

Non-Sentinel Lymph Node Metastasis Prediction in Breast Cancer with Metastatic Sentinel Lymph Node: Impact of Molecular Subtypes Classification

Introduction

To decipher the interaction between the molecular subtype classification and the probability of a non-sentinel node metastasis in breast cancer patients with a metastatic sentinel lymph-node, we applied two validated predictors (Tenon Score and MSKCC Nomogram) on two large independent datasets.

Materials and Methods

Our datasets consisted of 656 and 574 early-stage breast cancer patients with a metastatic sentinel lymph-node biopsy treated at first by surgery. We applied both predictors on the whole dataset and on each molecular immune-phenotype subgroups. The performances of the two predictors were analyzed in terms of discrimination and calibration. Probability of non-sentinel lymph node metastasis was detailed for each molecular subtype.

Results

Similar results were obtained with both predictors. We showed that the performance in terms of discrimination was as expected in ER Positive HER2 negative subgroup in both datasets (MSKCC AUC Dataset 1 = 0.73 [0.69–0.78], MSKCC AUC Dataset 2 = 0.71 (0.65–0.76), Tenon Score AUC Dataset 1 = 0.7 (0.65–0.75), Tenon Score AUC Dataset 2 = 0.72 (0.66–0.76)). Probability of non-sentinel node metastatic involvement was slightly under-estimated. Contradictory results were obtained in other subgroups (ER negative HER2 negative, HER2 positive subgroups) in both datasets probably due to a small sample size issue. We showed that merging the two datasets shifted the performance close to the ER positive HER2 negative subgroup.

Discussion

We showed that validated predictors like the Tenon Score or the MSKCC nomogram built on heterogeneous population of breast cancer performed equally on the different subgroups analyzed. Our present study re-enforce the idea that performing subgroup analysis of such predictors within less than 200 samples subgroup is at major risk of misleading conclusions.     

肾细胞癌淋巴结转移预测指标的Logistic 回归分析

目的:研究肾细胞癌淋巴结转移的危险因素,并建立Logistic回归模型。方法:2002年2月～2010年10月我院手术治疗的肾细胞癌163例,对其临床病理资料进行单因素和多因素的Logistic回归分析。结果:淋巴结转移的发生率为20.9%(34/163)。单因素分析显示:肿瘤大小、临床分期、Fuhrman核分级和贫血与肾细胞癌淋巴结转移的风险有关(P<0.05);多因素分析显示:肿瘤大小、临床分期和Fuhrman核分级是RCC淋巴结转移独立的风险因素。结论:肾细胞癌淋巴结转移的风险与肿瘤大小、临床分期和Fuhrman核分级有关,Logistic回归模型对于判断预后、指导术后治疗及随访方案的制订具有重要作用。     

肾细胞癌淋巴结转移预测指标的Logistic回归分析

目的：研究肾细胞癌淋巴结转移的危险因素,并建立Logistic回归模型。方法：2002年2月-2010年10月我院手术治疗的肾细胞癌163例,对其临床病理资料进行单因素和多因素的Logistic回归分析。结果：淋巴结转移的发生率为20．9％（34／163）。单因素分析显示：肿瘤大小、临床分期、Fuhrman核分级和贫血与肾细胞癌淋巴结转移的风险有关（P〈0．05）;多因素分析显示：肿瘤大小、临床分期和Fuhrman核分级是RCC淋巴结转移独立的风险因素。结论：肾细胞癌淋巴结转移的风险与肿瘤大小、临床分期和Fuhrman核分级有关,Logistic回归模型对于判断预后、指导术后治疗及随访方案的制订具有重要作用。     

双能量增强CT扫描对非小细胞肺癌纵隔淋巴结转移的诊断价值分析

目的:探讨双能量增强CT扫描诊断非小细胞肺癌(NSCLC)纵隔淋巴结转移的应用价值。方法:回顾性分析我院2017年5月至2019年5月接诊的100例行肺部双能量增强CT扫描的NSCLC患者临床资料,根据术后病理诊断是否发生纵膈淋巴结转移将患者转移组(42例)和未转移组(58例)。比较组间能谱曲线斜率(λHU)、淋巴结与原发癌灶能谱曲线斜率比值(简称斜率比值)、碘浓度(IC)、水浓度(WC)、标准化碘浓度(NIC)、标准化水浓度(NWC)差异,Logistic回归分析双能CT参数与NSCLC发生纵膈淋巴结转移的相关性,受试者工作特征曲线(ROC)分析双能CT参数诊断NSCLC发生纵膈淋巴结转移的效能。结果:转移组λHU、斜率比值、IC、NIC均低于未转移组(P0.05),转移组λHU、IC、WC、NIC、NWC与原发病灶比较均无统计学差异(P0.05),未转移组λHU、IC、NIC高于原发病灶(P0.05)。Logistic回归分析结果显示λHU、斜率比值、IC、NIC均与纵膈淋巴结转移有关(P0.05)。ROC分析结果显示λHU、斜率比值、IC、NIC诊断NSCLC纵膈淋巴结转移的AUC分别为0.849、0.871、0.838、0.860,灵敏度分别为80.95%、85.71%、78.57%、83.33%,特异度分别为79.31%、84.48%、81.03%、82.76%。结论:双能量增强CT扫描检查有助于提高NSCLC淋巴结转移准确率。     

宫颈癌腹主动脉旁淋巴结转移相关危险因素的研究分析

摘要 目的：分析上海市第一人民医院2015年至2019年期间250例分期为IB～IIA期的宫颈癌患者腹主动脉旁淋巴结（para-aortic lymph node,PALN）转移的危险因素,并探讨在早期宫颈癌手术中PALN清扫的意义。方法：回顾性分析250例宫颈癌患者的临床及病理资料,这些患者均接受了腹腔镜或开腹根治性子宫切除术+双侧盆腔淋巴结（pelvic lymph node,PLN）及PALN清扫术,采用统计学方法,通过单因素分析及多因素分析来讨论影响PALN转移的危险因素。结果：在250例宫颈癌患者中,PLN的转移率为27.60 %（69/250）,PALN的转移率为6.40 %（16/250）,在PLN转移阳性中,有15例PALN转移阳性的患者,转移率为21.74 %（15/69）。单因素分析显示,肿瘤最大直径、分期、淋巴脉管间隙浸润（lymph vascular space invasion,LVSI）、PLN转移以及鳞状上皮细胞癌抗原(SCC-Ag)与PALN转移有关（P＜0.05）,而多因素分析显示,分期为IIA期、PLN转移阳性以及PLN转移的个数≥3个是PALN转移的独立危险因素。将这些危险因素代入回归方程以建立临床预测模型,Y=-5.691+1.497×IIA期+3.627×PLN转移（Y代表PALN转移率）,利用受试者工作特征（receiver operating characteristic,ROC)曲线评估这些独立危险因素对于判断PALN转移是否具备一定的诊断价值,此时截断值（cut-off value）为0.064,灵敏度为93.80 %,特异度为76.90 %,曲线下面积（AUC）为0.907（P＜0.001,95 % CI：0.859～0.955）,H-L检验（Hosmer-Lemeshow）发现该模型拟合优度效果较好（P＞0.05）。同时通过绘制ROC曲线发现,当PLN转移个数≥3个以及肿瘤最大直径≥3.4 cm时,对判断是否存在PALN转移也具有一定的临床价值。结论：通过分析表明IIA期、PLN转移阳性以及转移个数≥3个是PALN转移的独立危险因素,可以对这些因素展开进行充分的评估与诊断,从而更加优化宫颈癌患者的分期、手术方式、治疗方案,为患者提供个体化临床诊疗,以期提高宫颈癌患者的生存质量,减少术后的并发症,改善患者的预后等。     

口腔癌中肿瘤出芽与VEGF—C表达及淋巴结转移的相关关系

目的：通过检测肿瘤出芽、淋巴结转移以及血管内皮生长因子-C（VEGF—C）表达水平,分析口腔癌中肿瘤出芽与VEGF—C表达及淋巴结转移的相关关系,为临床治疗提供理论参考。方法：选取2009年1月-2013年1月4年间在我院接受诊治且资料完整63例口腔癌患者作为研究对象,观察肿瘤出芽、VEGF-C表达和淋巴结转移情况,分析相互之间的相关关系。结果：本次纳入研究的患者中,检出肿瘤出芽患者40例,所占比例为63．5％,VEGF—C表达阳性患者39例,阳性率率为61．9％,淋巴结转移患者40例,转移率为63．5％;肿瘤出芽与淋巴结转移的符合率为84．1％,肿瘤出芽与VEGF—C的表达符合率为79．4％,VEGF-C的表达与淋巴结转移发生的符合率为76．2％。肿瘤出芽与淋巴结转移呈正相关,经Spear相关分析,r=0．932,P〈0．05,与VEGF-C的表达也呈正相关,经Spear相关分析,r=0．897,P〈0．05。结论：肿瘤出芽与VEGF—C的表达水平和淋巴结转移均呈正相关关系,可用于预测判断口腔癌淋巴结转移情况。     

MUC4 and MUC1 Expression in Adenocarcinoma of the Stomach Correlates with Vessel Invasion and Lymph Node Metastasis: An Immunohistochemical Study of Early Gastric Cancer

We have previously reported that MUC4 expression is a poor prognostic factor in various carcinomas. Our previous study also showed that MUC1 expression in gastric cancers, including the early and advanced stages is a poor prognostic factor. In the present study, the expression profiles of MUC4 and MUC1 were examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early gastric adenocarcinoma with submucosal invasion (pT1b2), including 197 histological subtype lesions. Before the IHC study of the human specimens, we evaluated the specificity of the two MAbs by Western blotting and IHC of two MUC4 mRNA expressing gastric cancer cell lines. MAb 8G7 reacted clearly, whereas MAb 1G8 did not show any reactivity, in either Western blotting or IHC. In the IHC of the gastric cancers, the expression rates of MUC4/8G7 detected by MAb 8G7, MUC4/1G8 detected by MAb 1G8 and MUC1/DF3 detected by MAb DF3 in well differentiated types (70%, 38/54; 67%, 36/54; 52%, 28/54) were significantly higher than those in poorly differentiated types (18%, 10/55; 36%, 20/55; 13%, 7/55) (P<0.0001; P = 0.0021; P<0.0001), respectively. The MUC4/8G7 expression was related with lymphatic invasion (r = 0.304, P = 0.033). On the other hand, the MUC4/1G8 expression was related with lymphatic invasion (r = 0.395, P = 0.001) and lymph node metastasis (r = 0.296, P = 0.045). The MUC1/DF3 expression was related with lymphatic invasion (r = 0.357, P = 0.032) and venous invasion (r = 0.377, P = 0.024). In conclusion, the expression of MUC4 as well as MUC1 in early gastric cancers is a useful marker to predict poor prognostic factors related with vessel invasion.     

RhoT1 and Smad4 Are Correlated with Lymph Node Metastasis and Overall Survival in Pancreatic Cancer

Cancer cell invasion and metastasis are the most important adverse prognostic factors for pancreatic cancer. Identification of biomarkers associated with outcome of pancreatic cancer may provide new approaches and targets for anticancer therapy. The aim of this study is to examine the relationship between the expression of RhoT1, Smad4 and p16 and metastasis and survival in patients with pancreatic cancer. The analysis showed that the high cytoplasmic expression levels of RhoT1, Smad4 and p16 in pancreatic cancer tissues had significantly negative correlation with lymph node metastasis (LNM) (P = 0.017, P = 0.032, P = 0.042, respectively). However, no significant association was observed between perineural invasion (PNI) and the expression of above three proteins (all P>0.05). Additionally, the survival analysis showed that the low expression levels of RhoT1 and Smad4 were significantly associated with worse survival (P = 0.034, P = 0.047, respectively). In conclusion, these results indicated that the low-expression levels of RhoT1 and Smad4 were significantly associated with LNM and shorter survival. RhoT1 may be considered as a potential novel marker for predicting the outcome in patients with pancreatic cancer.