Ⅲ期非小细胞肺癌纵隔淋巴结跳跃式转移的临床意义

目的探讨Ⅲ期非小细胞肺癌(NSCLC)患者纵隔淋巴结跳跃式转移的临床意义。方法65例术后病理证实的NSCLC患者,分为纵隔淋巴结(pN2期)跳跃转移组(21例)及非跳跃转移组(44例),回顾分析两组患者的临床、手术及病理资料。结果两组患者的性别、年龄及肿瘤的病理类型、大小、部位和术后转移情况差异无统计学意义(P均>0·05);非跳跃转移组发生多组淋巴结转移的概率为36.4%(16/44)显著高于跳跃转移组的9.5%(2/21;χ2=8·571,P=0·036)。跳跃转移组患者术后平均生存时间为44个月,5年生存率为41%;非跳跃转移组术后平均生存时间为26个月,5年生存率为21%,两者差异有统计学意义(χ2=9·325,P<0·05)。纵隔淋巴结跳跃式转移可以作为肺癌术后一个独立的预后因素(P=0·003,RR=0·347)。结论纵隔淋巴结跳跃式转移的临床Ⅲ期NSCLC患者生存期较无跳跃式转移的患者长,纵隔淋巴结跳跃式转移可以作为一个独立的生存预后因素;跳跃式转移可能是pN期肺癌中的一个亚群。     

A Proposal for Combination of Total Number and Anatomical Location of Involved Lymph Nodes for Nodal Classification in Non-small Cell Lung Cancer

BackgroundWe previously reported the prognostic impact of the number of involved lymph nodes (LNs) on survival in non-small cell lung cancer (NSCLC). However, it remains unknown whether the total number or anatomic location of involved LNs is a superior prognostic factor.MethodsA total of 689 patients with NSCLC who underwent complete resection involving dissection of the hilar and mediastinal LNs with curative intent of ≥ 10 LNs were enrolled. The association between the total number of LNs (nN) involved and survival was assessed by comparison with the anatomic location of LN involvement (pathologic lymph node [pN]), the present nodal category.ResultsWe classified the patients into five categories according to the combined pN and nN status as follows: pN0-nN0, pN1-nN1-3, pN1-nN4?, pN2-nN1-3, and pN2-nN4. Although there was no statistically significant difference between the pN1-nN4? and pN2-nN1-3 categories, pN2-nN1-3 had better prognoses than pN1-nN4?. On multivariate analysis, the nN category was an independent prognostic factor for overall survival and disease-free survival (vs nN4?; the hazard ratios of nN0 and nN1-3 for overall survival were 0.223 and 0.369, respectively, P < .0001 for all), similar to the pN category. We propose a new classification based on a combination of the pN and nN categories: namely, N0 becomes pN0-nN0, the N1 category becomes pN1-nN1-3, the N2a category becomes pN2-nN1-3 + pN1-nN4?, and the N2b category becomes pN2-nN4. Each survival curve was proportional and was well distributed among the curves.ConclusionsA combined anatomically based pN stage classification and numerically based nN stage classification is a more accurate prognostic determinant in patients with NSCLC, especially in the prognostically heterogeneous pN1 and pN2 cases. Further large-scale international cohort validation analyses are warranted.     

缺氧诱导因子-1α和血管内皮生长因子与非小细胞肺癌中临床病理特征和预后关系的研究

目的探讨缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)在非小细胞肺癌(NSCLC)术后双重表达的临床和预后意义,并研究HIF-1α抑制剂LW6和贝伐单抗(Avastin)对非小细胞肺癌细胞HIF-1α和VEGF表达的影响,初步探索HIF-1α与VEGF潜在的调控机制。方法采用免疫组化方法测定非小细胞肺癌组织中HIF-1α和VEGF的表达情况。用HIF-1α的抑制剂LW6和VEGF的抑制剂Avastin分别处理培养的非小细胞肺癌细胞系,采用western blotting检测HIF-1α和VEGF的表达。结合HIF-1α和VEGF的免疫组化结果和患者的临床病理资料进行统计分析。结果HIF-1α和VEGF双阳性表达与pT(P<0.05)、pN(P<0.01)和pTNM分期(P<0.01)及5年生存率(P<0.01)显著相关。在非小细胞肺癌细胞系中,用LW6处理缺氧细胞可以显著抑制HIF-1α的表达(P<0.01);用Avastin处理缺氧细胞对HIF-1α的表达无显著影响(P>0.05)。在缺氧细胞中,采用LW6或Avastin处理细胞均可抑制VEGF的表达。结论HIF-1α和VEGF双重表达能使我们更准确地预测非小细胞肺癌患者的预后,进一步验证在非小细胞肺癌中,HIF-1α是VEGF重要的上游调控者,参与VEGF表达调控。     

Effect of 3A lymph node resection on survival in patients with right-sided NSCLC: a retrospective,multicentre, propensity-score matching study

BackgroundWe aimed to assess the clinical significance and impact on survival of prevascular mediastinal lymph nodes (3A) in patients with right-sided lung cancer.MethodsProspective data of 6,348 patients, who underwent lung resection from 2005 to 2015, were retrospectively analysed. There were 221 patients who underwent 3A dissection (3ALN+), while 6,127 did not (3ALN−). We performed propensity score matching (PSM) to decrease selection bias (221 vs. 221).ResultsThe incidence of 3A metastasis was 8%, and it elevated with pT stage. Between pT1c and pT2a, there was a significant increase in the 3A metastasis incidence, which doubled from 4% to 9%. For pT4, the incidence was 15%. The highest incidence was found among patients undergoing pneumonectomy (10%) and in the N2b1 and N2b2 subgroups (33% and 64%). In univariable analysis, we found no differences in 5-year survival between 3ALN+ and 3ALN− (51% vs. 51%, P=0.74). But, non-metastatic 3ALN+, 3ALN−, and metastatic 3ALN+ differed significantly (P<0.0001). pN2 subgroups (pN2a1, pN2a2, pN2b1, pN2b2) within PSM analysis did not differ significantly in terms of survival. 3A metastasis failed to be an independent prognostic factor in the multivariable analysis of matched pN2 subgroups.ConclusionsRegardless of 3A lymph nodes failing to be an independent prognostic factor in our cohort, the incidence of metastases in lymph nodes increases notably in advanced stages. 3A metastasis rate is comparable to other lymph node stations. Therefore, superior mediastinal lymphadenectomy in advanced cancers may improve from resections of the 3A lymph node station.     

血管内皮生长因子表达与肺癌预后的相关性研究

目的　研究血管内皮生长因子（ 以下简称 Ｖ Ｅ Ｇ Ｆ） 表达与肺癌的预后相关性。方法　应用 Ｓ Ｐ 免疫组化方法研究 Ｖ Ｅ Ｇ Ｆ 在６０ 例肺癌患者组织中的表达。结果　 Ｖ Ｅ Ｇ Ｆ 阳性表达率为６０ ％ , Ｖ Ｅ Ｇ Ｆ阳性表达主要出现在肺癌组织中癌细胞胞浆内, Ｖ Ｅ Ｇ Ｆ 表达与肺癌的淋巴结转移、复发有关：其中 Ｎ１ 、 Ｎ２（ ＋ ） 组 Ｖ Ｅ Ｇ Ｆ 阳性率分别为５３ ％ 、８０ ％ ,高于 Ｎ０ 组（２３ ％ , Ｐ＜ ００１） , Ｖ Ｅ Ｇ Ｆ 阳性表达率在肺癌复发组（８０ ％ ） 高于无复发组（５３ ％ , Ｐ＜ ００５） ;３ 、５ 年生存率 Ｖ Ｅ Ｇ Ｆ（ ＋ ） 与 Ｖ Ｅ Ｇ Ｆ（ － ） 组分别为３１ ％ 、１１ ％ 和８８ ％ 、５０ ％ ;术后生存时间 Ｖ Ｅ Ｇ Ｆ 表达（ ＋ ） 组远低于 Ｖ Ｅ Ｇ Ｆ 表达（ － ） 组（ 分别为３１ ±７ 月,６４ ±７月, Ｐ＜ ００５） 。结论　 Ｖ Ｅ Ｇ Ｆ是促进肺癌组织血管生成的关键因素,是预测肺癌患者预后的重要指标。     

Caveolin-1在结直肠癌组织间质中的表达及临床意义

目的探讨小凹蛋白（Caveolin-1,Cav-1）在结直肠癌组织中的表达及临床意义。 方法收集在我院手术的结直肠癌患者110例,用免疫组化的方法检测Cav-1蛋白的表达。 结果Cav-1阳性表达于肿瘤细胞的胞浆或胞膜上,低表达样本51例,高表达样本59例。Cav-1蛋白的表达与肿瘤N分期（P=0.011）及TNM分期密切相关（P=0.031）。Cav-1低表达患者的总体生存率及无进展生存率明显优于Cav-1高表达患者（P均小于0.001）。 结论Cav-1或可以作为估计结直肠癌患者预后的指标之一,这也可能为结直肠癌患者的治疗提高新的方向。     

Measurement of circulating levels of VEGF-A, -C, and -D and their receptors, VEGFR-1 and -2 in gastric adenocarcinoma

AIM： TO analyze the serum levels and prognostic significance of vascular endothelial growth factor （VEGF） -A, -C, and -D, and their receptors, VEGFR-1 and -2 in gastric adenocarcinomas. METHODS： The serum levels of VEGF family members were measured in 76 control subjects and 76 patients with gastric adenocarcinoma using an enzyme-linked immunosorbent assay （ELISA）. These measurements were correlated with clinco-pathological features and survival rates. RESULTS： The serum levels of VEGF-A and its receptor, VEGFR-1, were significantly higher in patients with gastric cancer than in healthy donors （t = 2.3, P = 0.02 and t = 4.2, P 〈 0.0001, respectively）. In contrast, the serum levels of VEGF-D were significantly higher in control subjects than in patients （t = 2.9, P = 0.004）. There was no significant difference in serum levels of VEGF-C and VEGFR-2 between patients and controls. VEGF-C was associated with advanced tumor stage and presence of metastasis. VEGFR-1 was associated with metastasis, advanced overall stage,tumor differentiation and survival. VEGFR-2 levels were associated with poor tumor differentiation. There was no significant prognostic value for any of the VEGF family members or their receptors except for VEGFR-1 where high levels were associated with a poor overall survival. CONCLUSION： Serum VEGF levels vary significantly in the same cohort of patients with variable clinicopathological features and prognostic values. The simultaneous measurement of VEGF receptors levels in sera may overcome the limitations of a single biomarker assay.     

VEGF和MVD可作为判断胃癌患者预后和上消化道出血风险的指标

背景:血管内皮生长因子(VEGF)是主要血管生成调控因子之一,与肿瘤血管发生密切相关,微血管密度(MVD)是评价肿瘤血管发生的重要指标。有研究发现VEGF表达和MVD与胃癌患者的上消化道出血(UGIB)风险相关。目的:探讨VEGF和MVD与胃癌患者临床病理特征、预后和UGIB风险的关系。方法:收集60例伴或不伴UGIB胃癌患者的胃癌手术标本石蜡包埋组织,以免疫组化方法检测VEGF表达和MVD(计数CD34阳性血管内皮细胞)。结果:胃癌组织VEGF阳性表达率为51.7%(31/60),MVD均值为35.18±19.72。伴UGIB的胃癌患者VEGF阳性表达率和MVD均值显著高于不伴UGIB者(VEGF:64.5%对37.9%,P<0.05;MVD:42.70±15.50对27.13±20.80,P<0.01)。VEGF表达和MVD均与胃癌T分期和pTNM分期呈正相关(P<0.01),VEGF表达与肿瘤组织分化呈负相关(P<0.05),MVD与N分期呈正相关(P<0.001)。COX多元回归分析显示MVD是影响胃癌患者术后生存时间的危险因素,而VEGF与术后生存时间无关。结论:VEGF表达和MVD与胃癌患者的临床病理进展和UGIB风险相关,MVD为胃癌患者术后生存时间的重要影响因素,两者可共同作为判断胃癌患者预后和UGIB风险的有效指标。     

Clinicopathological and prognostic significance of galectin-1 and vascular endothelial growth factor expression in gastric cancer

AIM: To evaluate the expression of galectin-1 and vascular endothelial growth factor (VEGF) in gastric cancer and investigate their relationships with clinicopathologic factors and prognostic significance. METHODS: Galectin-1 and VEGF were immunohistochemically investigated in tumor samples obtained from 214 gastric cancer patients with all tumor stages. Immunohistochemical analyses for galectin-1 and VEGF expression were performed on formalin-fixed, paraffin-embedded sections of surgical specimens. The relationship between the expression and staining intensity of galectin-1 and VEGF, clinicopathologic variables, and patient survival were analyzed. All patients underwent follow-up until cancer-related death or more than five years after tumor resection. P values < 0.05 were considered statistically significant.RESULTS: Immunohistochemical staining demonstrated that 138 of 214 gastric cancer samples (64.5%) were positive for galectin-1, and 116 out of 214 gastric cancer samples (54.2%) were positive for VEGF. There was a significant association between galectin-1 and VEGF expression; VEGF was detected in 60.1% of galectin-1-positive samples and 43.4% of galectin-1-negative samples (P < 0.05). Galectin-1 expression was associated with tumor size, tumor location, stage, lymph node metastases, and VEGF expression (all P < 0.05). VEGF expression was related to tumor size, stage, and lymph node metastases (all P < 0.05). The 5-year survival rate was 56.6% for galectin-1-positive patients and 69.2% for galectin-1-negative patients, and the prognosis for galectin-1-positive patients was significantly poorer compared with galectin-1-negative patients (χ 2 = 13.880, P = 0.000). The 5-year survival rates for VEGF-positive and VEGF-negative patients were 53.4% and 70.5%, respectively (χ2 = 4.619, P = 0.032). The overall survival rate of patients with both galectin-1 and VEGF overexpression in gastric cancer tissue samples was significantly poorer than other groups (both P < 0.05).CONCLUSION: Galectin-1 expr     

Correlation between survivin expression and prognosis in non-small cell lung cancer

AIMS AND BACKGROUND: Survivin is a recently identified protein as an inhibitor of apoptosis, which supresses programmed cell death and regulates cell division. In this study, we investigated the prognostic significance of both nuclear and cytoplasmic survivin expression in non-small cell lung cancer (NSCLC) and examined the association with clinicopathological parameters. METHODS: The study comprised 58 male patients diagnosed NSCLC with a mean age of 57.29+/-8.82 years; range 40-76 years. Patients underwent lobectomy (64%) or pneumonectomy (36%) with hilar and mediastinal lymph node sampling. Paraffin embedded tumor sections were retrieved for evaluation of nuclear and cytoplasmic staining of survivin. Clinicopathological data, stage and survival of patients were all determined. RESULTS: Cytoplasmic staining was found significantly increased in squamous cell carcinoma (P=0.003), whereas there was no association between nuclear staining and histopathological type (P=0.837). Also, both nuclear and cytoplasmic staining did not show any association with tumor stage (P>0.05). In univariate analysis there was significant correlation between nuclear survivin and short survival (P=0.0002). In multivariate survival analysis using Cox regression, only nuclear staining of survivin was determined as an independent prognostic factor (P=0.004). CONCLUSIONS: Localization of survivin expression might have an important regulatory mechanism in carcinogenesis and tumor progression. Nuclear survivin expression in tumor tissues might predict the prognosis in NSCLC, whereas cytoplasmic survivin has no prognostic significance.     

Prognostic significance of VEGF immunohistochemical expression and tumor angiogenesis in head and neck squamous cell carcinoma

PURPOSE: Tumor angiogenesis is crucial for both the growth of the primary tumor and the development of metastases. Among the factors causing tumor angiogenesis, vascular endothelial growth factor (VEGF) is considered as a leading candidate. We aimed to assess the prognostic significance of VEGF and tumor angiogenesis in head and neck squamous cell carcinoma (HNSCC). METHODS: We performed a retrospective study of 69 patients with HNSCC, in order to investigate whether VEGF immunohistochemical expression and tumor angiogenesis correlate with clinicopathological parameters and outcome. Tumor angiogenesis was estimated by determining microvessel density (MVD), and VEGF expression was assessed quantitatively. RESULTS: Vascular endothelial growth factor and MVD correlated statistically significant with the clinical stage, but not with the presence of lymph node metastasis at the time of diagnosis. Tumors located in the oral cavity and larynx more often expressed high VEGF immunostaining compared with tumors located in the lower lip. High VEGF expression was associated with higher clinical stage and worse overall survival in this cohort of patients. CONCLUSIONS: Vascular endothelial growth factor expression may have prognostic significance for patients with HNSCC.     

Angiogenesis and cathepsin expression are prognostic factors in pancreatic adenocarcinoma after curative resection.

BACKGROUND: Curative resection of pancreatic adenocarcinoma is the only clinical parameter related to a favorable prognosis while other clinicopathological parameters fail. To evaluate whether angiogenesis, vascular endothelial growth factor (VEGF) or certain tumor proteases, e.g., cathepsin B (CTSB) and L (CTSL), are factors of prognostic relevance, we investigated their expression in patients with long- and short-term survival after curative resection (RO) because of pancreatic adenocarcinoma. METHODS: Twenty-nine tissue samples from patients with adenocarcinoma of the pancreas were examined. The patients were selected in a long-term survival group with a survival > or = 24 mo (n = 18) and a shortterm survival group of patients, who died within 8 mo after surgery because of their malignancy (n = 11). The microvessel quantification was performed immunohistochemically using a monoclonal anti-CD34 antibody. VEGF, CTSB, and CTSL expressions was studied using polyclonal antibodies (PAbs). RESULTS: The median microvessel density (MVD) was 75 (range 39-182). MVD correlated significantly with the survival time after surgery (p = 0.0132) but not with clinicopathological parameters. In cancer cells, VEGF was positive in 82.8% and showed significant correlation with the MVD (p = 0.0002) and survival time (p = 0.0395). Positive immunoreactivity could be obtained for 96.5% for CTSB and 84.2% for CTSL. Expression of both proteases correlated significantly with the survival time after surgery (CTSB p = 0.0002, CTSL p = 0.0001). Furthermore, CTSB expression correlated with invasion of the perineural space. Thus, a short postoperative survival correlated with a high MVD, and highly expressed VEGF, CTSB, and CTSL. No significant correlation between MVD, VEGF, as well as CTSL and clinicopathological parameters was found. For routinely assessed markers (e.g., TNM-stage, UICC-stage, and so on) no significant correlation with survival time was found in this small group of patients. CONCLUSION: These findings indicate that the MVD, VEGF, CTSB, and CTSL are prognostic factors after curative resection, whereas other parameters (TNM, UICC, and so on) failed to show prognostic relevance in our group of patients. Furthermore, the correlation between MVD and VEGF underlines the importance of this growth factor for angiogenesis and tumor growth. The correlation between CTSB and perineural invasion demonstrates the involvement of cathepsins in local tumor invasion.     

长链非编码RNA ZNF667-AS1在非小细胞肺癌组织中表达上调

目的:探讨非小细胞肺癌（NSCLC）组织中长链非编码RNA（lncRNA） 锌指蛋白667反义RNA1（ZNF667-AS1）的表达水平。方法： 97例NSCLC患者被纳入本研究，术中留取新鲜的癌组织及对应癌旁组织，采用实时定量聚合酶链式反应（PCR）法检测lncRNA ZNF667-AS1和血管内皮生长因子（VEGF）的表达，分析lncRNA ZNF667-AS1的表达与NSCLC患者临床病理特征的关系，绘制受试者工作特征（ROC）曲线，评估lncRNA ZNF667-AS1用于诊断NSCLC的价值，分析癌组织中VEGF的表达与lncRNA ZNF667-AS1表达的相关性。结果：PCR检测结果显示，97例NSCLC患者癌组织中lncRNA ZNF667-AS1的平均相对表达量明显高于癌旁组织（P<0.05）。不同性别、年龄、肿瘤直径及病理组织类型的NSCLC患者癌组织中lncRNA ZNF667-AS1相对表达量比较，差异无统计学意义（P均＞0.05），但不同组织分化程度、临床分期、浸润程度及有无淋巴结转移的患者癌组织中lncRNA ZNF667-AS1相对表达量比较，差异有统计学意义（P均<0.05）。实时荧光定量PCR检测结果显示，NSCLC癌组织中VEGF的相对表达量明显高于癌旁组织（P<0.01），NSCLC癌组织中lncRNA ZNF667-AS1的相对表达量与VEGF的表达呈正相关（P<0.05）。由ROC曲线可知，lncRNA ZNF667-AS1诊断NSCLC的AUC为0.792（95%CI：0.683-0.911，P﹤0.05），特异性为81.23%，敏感度为86.12%。结论： lncRNA ZNF667-AS1在NSCLC组织中表达上调，其可能作为一种促癌因子参与NSCLC的发生发展过程。     

Loss of stromal caveolin-1 expression in colorectal cancer predicts poor survival

AIM: To investigate the clinicopathological significance and prognostic value of caveolin-1(CAV-1) in both tumor and stromal cells in colorectal cancer(CRC).METHODS: A total of 178 patients with CRC were included in this study. The correlation between CAV-1expression and clinicopathologic features and survival was studied.RESULTS: CAV-1 expression was detected in tumor and stromal cells. The expression of stromal CAV-1 was closely associated with histological type(P = 0.022), pathologic tumor-node-metastasis stage(P = 0.047), pathologic N stage(P = 0.035) and recurrence(P = 0.000). However, tumor cell CAV-1 did not show any correlation with clinical parameters. Additionally, the loss of stromal CAV-1 expression was associated with shorter disease-free survival(P = 0.000) and overall survival(P = 0.000). Multivariate analysis revealed that the loss of stromal CAV-1 expression was an independent prognostic factor for both overall survival(P = 0.014) and disease-free survival(P = 0.006).CONCLUSION: The loss of stromal CAV-1 expression in CRC was associated with poor prognosis and could be a prognostic factor for CRC patients.     

EphA2, vascular endothelial growth factor,and vascular endothelial growth factor correlate with adverse outcomes and poor survival in patients with glioma

Purpose:To assess expression levels of Ephrin type-A receptor 2 (EphA2), vascular endothelial growth factor (VEGF), and von Willebrand factor (vWF), and assess their potentials as prognostic biomarkers to predict the risk of poor survival in patients with primary lower grade glioma.Method:The study included75 patients with histopathologically confirmed primary glioma (World Health Organization Grade IV). All patients underwent combined surgery and postoperative radiotherapy for the management of primary glioma. Immuno-histochemical analysis was performed to evaluate expression levels ofEphA2 and VEGF. Evaluation of tumor microvessel density was also performed at angiogenesis hot spots due to tumor growth. Main outcomes of the study were the prognostic efficiencies of EphA2, VEGF, and vWF in primary low-grade glioma, as well as whether their expression levels were associated with cancer progression.Results:Of the patients with glioma, 67% had very strong expression of EphA2. Overall survival was inversely correlated with the expression of EphA2. Regarding VEGF expression, 38 patients (51%) had strong expression, 29 patients (39%) had weak expression, and 8 patients (11%) had no expression. Strong VEGF expression was associated with poor prognosis and poor survival.Conclusion:EphA2, VEGF, and vWF could be considered prognostic markers for assessment of primary glioma.     

Ki-67 labeling index as an independent prognostic factor in human esophageal squamous cell carcinoma

Background

Although the Ki-67 labeling index (LI) is frequently used to determine the proliferative activity of malignant tumors, no consensus has been reached about its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). In this study, we sought to determine an adequate Ki-67 LI cutoff value and investigated its prognostic significance in ESCC.

Methods

The Ki-67 LI was calculated by immunohistochemistry for 49 primary tumor samples obtained from ESCC patients who had undergone curative esophagectomy, and the correlations between the Ki-67 LI and various clinicopathological features or prognosis were analyzed.

Results

The Ki-67 LI of the tumors ranged from 5.3 to 55.9?%. The mean Ki-67 LI increased from 27.4?% in pN0 tumors to 40.3?% in pN3 tumors. The 5-year survival rate decreased as the Ki-67 LI increased. When the patients were divided into two groups using an Ki-67 LI cutoff value of 35?%, the 5-year survival rate of the patients with Ki-67 LI of <35?% was 82.9?%, which was significantly higher than that of the patients with Ki-67 LI of ??35?% (35.7?%). The percentage of pN-positive tumors was significantly higher among the patients with Ki-67 LI of ??35?% (85.7?%) than in patients with Ki-67 LI of <35 (48.6?%). Multivariate analysis demonstrated that pT and pN categories and the Ki-67 LI were independent prognostic factors.

Conclusions

These observations indicate that the Ki-67 LI is correlated with lymph node metastasis and can be used as an independent prognostic factor for ESCC patients by selecting an adequate cutoff value.     

A new classification system for liver metastases from colorectal cancer in Japanese multicenter analysis

BACKGROUND/AIMS: Although numerous authors have reported various prognostic factors for liver metastases from colorectal cancer, there is not yet a general classification. METHODOLOGY: A total of 478 colorectal cancer patients from 18 institutes were studied. Prognostic factors were investigated using univariate and multivariate analyses. RESULTS: Independent prognostic factors for colorectal liver metastases were number of liver metastases, size of the largest liver metastases, mesenteric lymph node metastases (pN0/1: < or =3 lesions, pN2: > or =4 lesions), and extrahepatic metastases (EM0: absence of extrahepatic metastasis, EM1: presence of extrahepatic metastases). We defined the following classification system; Stage A: HT1 (< or =4 lesions and < or =5cm) and pN0/1, Stage B: HT2 (> or =5 lesions or >5cm) and pN0/1, or HT1 and pN2, Stage C: HT2 and pN2, HT3 (> or =5 lesions and >5cm) with any pN, or any HT and any pN with EM1. Five-year survival rates were 53.5% for Stage A patients, 25.4% for Stage B patients, and 5.8% for Stage C patients. Median survival time was 70.4 months, 31.4 months, and 17.2 months, respectively. CONCLUSIONS: Our classification was advocated to evaluate prognoses for liver metastases from colorectal cancer. It can help guide decision making in terms of liver resection and assessing patient prognosis.     

Endocan-expressing microvessel density as a prognostic factor for survival in human gastric cancer

AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor (VEGF) and prognosis in gastric cancer.METHODS: This study included 142 patients with confirmed gastric cancer in a single cancer centre between 2008 and 2009. Clinicopathologic features were determined, and an immunohistochemical analysis of endocan-expressing microvessel density (MVD) (endocan-MVD), VEGF and vascular endothelial growth factor receptor 2 (VEGFR2) was performed. Potential relationships between endocan-MVD and clinicopathological variables were assessed using a Student’s t-test or an analysis of variance test. Spearman’s rank correlation was applied to evaluate the relationship between endocan-MVD and the expression of VEGF/VEGFR2. Long-term survival of these patients was analysed using univariate and multivariate analyses.RESULTS: Positive staining of endocan was observed in most of the gastric cancer tissues (108/142) and in fewer of the normal gastric tissues. Endocan-MVD was not associated with gender or histological type (P > 0.05), while endocan-MVD was associated with tumour size, Borrmann type, tumour differentiation, tumour invasion, lymph node metastasis and TNM stage (P < 0.05). According to the Spearman’s rank correlation analysis, endocan-MVD had a positive correlation with VEGF (r = 0.167, P = 0.047) and VEGFR2 (r = 0.410, P = 0.000). The univariate analysis with a log-rank test indicated that the patients with a high level of endocan-MVD had a significantly poorer overall survival rate than those with a low level of endocan-MVD (17.9% vs 64.0%, P = 0.000). The multivariate analysis showed that a high level of endocan-MVD was a valuable prognostic factor.CONCLUSION: Endocan-MVD significantly correlates with the expression of VEGF and VEGFR2 and is a valuable prognostic factor for survival in human gastric cancer.     

Increased Expression of CSF-1 Associates With Poor Prognosis of Patients With Gastric Cancer Undergoing Gastrectomy

Clinical significance of diametrically polarized tumor-associated macrophages in gastric cancer has been elucidated in our previous study, whereas the role of cytokines that orchestrate tumor-associated macrophages polarization in gastric cancer remains elusive. The study aims to evaluate the prognostic value of colony-stimulating factor-1 expression in patients with gastric cancer.We examined the colony-stimulating factor-1 expression in tumor tissues by immunohistochemical staining in retrospectively enrolled 365 patients with gastric cancer undergoing gastrectomy at Zhongshan Hospital during 2008. Kaplan–Meier analysis and Cox regression models were used to evaluate the prognostic value of colony-stimulating factor-1 expression and its association with clinicopathological factors. A predictive nomogram by integrating colony-stimulating factor-1 expression with the TNM staging system was generated for overall survival evaluation of the patients.High colony-stimulating factor-1 expression predicted an unfavorable outcome in gastric cancer. The colony-stimulating factor-1 expression in tumor tissue could give a further discrimination for the prognosis of gastric cancer patients. Cox multivariate analysis identified the colony-stimulating factor-1 expression as an independent prognostic factor. The generated nomogram performed well in predicting the 3- and 5-year overall survival of gastric cancer patients.The colony-stimulating factor-1 is a potential independent adverse prognosticator for gastric cancer patients, which could be integrated with the tumor-associated macrophages staging system to improve the predictive accuracy for overall survival, especially in advanced tumors.     

Cyclooxygenase-2 expression after preoperative chemoradiotherapy correlates with more frequent esophageal cancer recurrence

AIM: To investigate the relationship between cycloo- xygenase-2 (COX-2), and vascular endothelial growth factor (VEGF), and to determine the clinical significance of this relationship in esophageal cancer patients undergoing chemoradiotherapy (CRT). METHODS: Immunohistochemical staining was used to evaluate COX-2 and VEGF expression in 40 patients with histologically-confirmed esophageal squamous carcinoma (ESCC) who were undergoing preoperative CRT. RESULTS: Fourteen out of 40 ESCC patients showed a pathological complete response (CR) after CRT. COX-2 and VEGF protein expressions were observed in the cytoplasm of 17 and 13 tumors, respectively, with null expression in 9 and 13 tumors, respectively. COX-2 expression was strongly correlated with VEGF expression (P < 0.05). There were also significant associations between COX-2 expression, tumor recurrence, and lymph-node involvement (P = 0.0277 and P = 0.0095, respectively). COX-2 expression and VEGF expression had significant prognostic value for disease-free survival (log-rank test; P = 0.0073 and P = 0.0341, respectively), but not for overall survival, as assessed by univariate analysis. CONCLUSION: Our results suggest that COX-2 expression correlates with VEGF expression and might be a useful prognostic factor for more frequent tumor recurrence in ESCC patients undergoing neoadjuvant CRT. These findings support the use of anti-angiogenic COX-2 inhibitors in the treatment of ESCC.