Clinicopathological significance of vascular endothelial growth factor-C and cyclooxygenase-2 in esophageal squamous cell carcinoma

BACKGROUND: Vascular endothelial growth factor-C (VEGF-C) is a specific growth factor of lymphatics, which is known to play some role in tumor growth and metastasis to lymph nodes and distant organs in various malignancies. The purpose of the present study was to investigate the expression of VEGF-C in human esophageal squamous cell carcinomas (ESCC) to elucidate its role in tumor progression and lymph node metastasis. Another aim of the study was to investigate the relation between VEGF-C and cyclooxygenase-2 (COX-2) in ESCC. METHODS: The expression of VEGF-C and COX-2 in ESCC was evaluated in 13 endoscopic mucosal resection specimens and in 21 surgical specimens by immunohistochemical staining. Clinical data were obtained from medical records. RESULTS: The degree of VEGF-C expression increased as the depth of primary tumor progressed (r = 0.521, P = 0.002), the stage progressed (r = 0.572, P < 0.001), and the degree of COX-2 expression increased (r = 0.387, P = 0.024). The VEGF-C positive rate was different between early cancers in which regional lymph node metastasis was thought to be absent and advanced cancers in which regional lymph node metastases were confirmed after surgery (20.0% vs 100.0%; P < 0.001). CONCLUSIONS: The VEGF-C expression in ESCC is related to COX-2 expression, and VEGF-C is also associated with the depth of primary tumor, the stage, and probably lymph node metastasis. Thus the investigation of VEGF-C expression in ESCC may assist in management planning.     

胃癌组织血小板衍化内皮细胞生长因子的表达与血管生成和凋亡的关系

目的探讨血小板衍化内皮细胞生长因子（PD．ECGF）在胃癌组织中的表达及与血管生成和凋亡的关系。方法应用免疫组化技术对67例胃癌组织进行PD－ECGF表达、肿瘤组织微血管密度（MVD）检测，流式细胞技术检测胃癌组织细胞凋亡指数（川，凋亡百分率八结果＊r＊＊＊F的表达与胃癌淋巴结转移（P＜0．oj）。分化程度（P＜0．05）及组织分型（P＜0．05）显著相关，与＊V则尸＜001）和胃癌细胞凋亡指数（P＜001）显著相关。＊＊D和＊1与淋巳结转移（P＜001）显著相关。结论胃癌组织中P＊。 ECGF可促进血管生成，抑制胃癌细胞凋亡，促进胃癌的增殖与转移。     

Expression of vascular endothelial growth factor C and chemokine receptor CCR7 in gastric carcinoma and their values in predicting lymph node metastasis

AIM: To study the expression of vascular endothelial growth factor C (VEGF-C) and chemokine receptor CCR7 in gastric carcinoma and to investigate their associations with lymph node metastasis of gastric carcinoma and their values in predicting lymph node metastasis. METHODS: The expression of VEGF-C and CCR7 in gastric carcinoma tissues obtained from 118 patients who underwent curative gastrectomy was examined by immunohistochemistry. Among these patients, 39 patients underwent multi-slice spiral CT (MSCT) examination. RESULTS: VEGF-C and CCR7 were positively expressed in 52.5 and 53.4% of patients. VEGF-C expression was more frequently found in tumors with lymph node metastasis than those without it (P<0.001). VEGF-C expression was also closely related to lymphatic invasion (P<0.001), vascular invasion (P<0.01), and TNM stage (P<0.001). However, there was no significant correlation between VEGF-C expression and age at surgery, gender, tumor size, tumor location, Lauren classification, and depth of invasion. CCR7 expression was significantly higher in patients with lymph node metastasis compared with those without lymph node metastasis (P<0.001) and was also associated with tumor size (P<0.01), depth of invasion (P<0.001), lymphatic invasion (P<0.001), and TNM stage (P<0.001). However, the presence of CCR7 had no correlation to age at surgery, gender, tumor location, Lauren classification, and vascular invasion. Among the 39 patients who underwent MSCT examination, only CCR7 expression was related to lymph node metastasis determined by MSCT (P<0.05). In the current retrospective study, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of VEGF-C and CCR7 expression in the diagnosis of lymph node metastasis for patients with gastric carcinoma were 73.8%, 70.2%, 72.6%, 71.4% and 72.0%, and 82.0%, 77.2%, 79.4%, 80.0% and 79.7%, respectively. After subdivision according to the combination of VEGF-C and CCR7 expression, receiver operating characteristic (ROC) analysis showed that the accuracy of the combined examination of VEGF-C and CCR7 expression in predicting lymph node metastasis was relatively high (area under ROC curve [Az]=0.83). CONCLUSION: The expression of VEGF-C and CCR7 is related to lymph node metastasis of gastric carcinoma and both of them may become new targets for the treatment of gastric carcinoma. Furthermore, the combined examination of VEGF-C and CCR7 expression in endoscopic biopsy specimens may be useful in predicting lymph node metastasis of gastric carcinoma and deciding the extent of surgical lymph node resection.     

血管内皮生长因子与血小板衍化内皮细胞生长因子在老年人胃癌组织中的表达

目的　探讨老年人胃癌术前活检标本血管内皮生长因子 (VEGF)和血小板衍化内皮细胞生长因子 (PD ECGF)的表达及其与老年胃癌患者预后的关系。　方法　采用免疫组化法检测 92例老年胃癌VEGF、PD ECGF表达情况 ,并分析它们与胃癌临床病理特征关系及对预后的影响。　结果　VEGF、PD ECGF在胃癌组织的表达明显高于慢性萎缩性胃炎 ,进展期癌的表达又高于早期癌(P <0 0 1) ,VEGF、PD ECGF表达呈显著正相关 (相关系数R =0 4 0 5 4 )。VEGF、PD ECGF的阳性表达随着肿瘤大小、浸润深度、TNM分期的递增而呈上调表达 ,有淋巴结转移、血管癌栓的患者表达也明显高于无淋巴结转移、血管癌栓者 (P <0 0 1)。VEGF、PD ECGF阳性表达者总体生存率明显低于VEGF、PD ECGF阴性表达者 (P <0 0 1) ,VEGF、PD ECGF共同表达者生存率更低 (P <0 0 1)。多因素分析表明 ,淋巴结转移、TNM分期、VEGF的表达是老年人胃癌独立的预后因素。　结论　VEGF与PD ECGF表达呈正相关 ,均与胃癌生长、浸润转移关系密切 ,可作为估计老年人胃癌预后的重要因素。     

结肠癌血管生成相关因子的表达及其意义的研究

目的研究VEGF配体及其受体在结肠癌发生、发展、转移中的作用,探讨VEGF家族与结肠癌各个时期病理特征的关系。方法在肿瘤标本,癌旁及正常组织标本中,用半定量RT-PCR方法,测定各种标本中VEGF各配体及VEGF受体表达,以研究它们在结肠癌进程中的作用。同时用免疫组化方法,对上述因子进行研究。结果 (1)与正常组织相比,VEGF-A、VEGF-C在肿瘤组织中显著升高(P<0．01);VEGF-B在肿瘤和正常组织中表达相近,而VEGF-D在肿瘤组织中显著降低;(2)VEGF-A、VEGF-B、VEGF-C在有淋巴结转移的肿瘤中明显升高(P<0．01);VEGF-D在有淋巴结转移的肿瘤中下降,但没有统计学差异。(3)VEGFR-1与Duke's分期,淋巴结转移显著相关(P<0．01);VEGFR-2与淋巴结转移显著相关(P<0．01);VEGFR-3与临床病理特征均不相关;VEGFR-1在肿瘤组织比正常组织升高(P<0．01),但VEGFR-2和VEGFR-3表达在肿瘤进程中没有显著升高。结论 VEGF-A、VEGF-B与结肠癌早期发展过程相关,VEGF-C、VEGFR-1与结肠癌进展过程相关,并和VEGF-D、VEGFR-2共同参与转移过程。     

Angiogenesis and lymphangiogenesis in parathyroid proliferative lesions

Angiogenesis and lymphangiogenesis are involved in tumoral growth and metastatic spread. There is little information on angiogenesis and no available data on lymphangiogenesis in parathyroid glands (PTG). Using immunohistochemistry for CD34, LYVE-1 (specific markers for vascular and lymphatic endothelium, respectively), vascular endothelial growth factor (VEGF)-A, VEGF-C, and fibroblast growth factor (FGF)-2, this study analyzes microvascular density (MVD), lymphatic vascular density (LVD), and expression of angiogenic and lymphangiogenic growth factors in 13 normal PTG, 77 parathyroid adenomas (PTA), and 17 primary parathyroid hyperplasia (PPH). MVD was higher in PPH and PTA, compared with PTG (P < 0.001). There was no difference in VEGF-A expression among groups. In contrast, FGF-2 expression was higher in PPH, compared with PTA and PTG (P < 0.0001). FGF-2 scores and MVD were significantly correlated (r = 0.43). LVD did not differ among groups, and VEGF-C expression was unrelated to LVD. There was no relationship between MVD and tumor behavior (adenoma size, PTH, or calcium). In conclusion, this study shows increased angiogenesis in parathyroid proliferative lesions compared with normal glands and suggests that FGF-2 is proangiogenic in parathyroid tissue. In PTA, tumor behavior is not related to angiogenic phenotype. This is the first demonstration of lymphatic vessels in PTG, but the lack of correlation with VEGF-C expression suggests that VEGF-C is not the primary lymphangiogenic factor.     

Prognostic significance of erythropoietin and erythropoietin receptor in gastric adenocarcinoma

AIM: To investigate the expression of Erythropoietin (Epo) and its receptor (EpoR) in gastric adenocarcinoma (GAC) and the correlation with angiogenesis and clinicopathological features. METHODS: The expressions of Epo, EpoR and vascular endothelial growth factor (VEGF), as well as microvessel density were evaluated in 172 GAC biopsies by immunohistochemical staining. The correlations between these parameters and patient’s clinicopathological features were analyzed statistically. RESULTS: The proportion of ...     

Vascular endothelial growth factor C (VEGF-C) expression in pT2 gastric cancer

BACKGROUND/AIMS: The purpose of this study was to determine whether the vascular endothelial growth factor C (VEGF-C) protein expression was related to the clinicopathologic features of patients with pT2 (primary tumor invasion of muscularis propria or subserosa) gastric cancer. METHODOLOGY: The expression of VEGF-C protein was investigated retrospectively in 102 patients with pT2 gastric cancer. Immunohistochemical staining of the paraffin sections was performed using a polyclonal antibody to VEGF-C. RESULTS: Normal gastric mucosa was not immunoreactive with an anti-VEGF-C antibody. Among the 102 tumors examined, 27 (26.5%) showed high expression of VEGF-C protein. No staining was observed in the normal tissue surrounding the tumor. There were no significant differences in age, gender, or histological types. With regard to the clinicopathological characteristics, significant differences were observed in depth of tumor invasion (muscularis propria vs. subserosa; p<0.05), lymph node metastasis (p<0.001), and stage grouping (p<0.001). The prognosis for VEGF-C-positive patients was worse than that for VEGF-C-negative patients in terms of overall survival, and VEGF-C expression was an independent prognostic indicator (p=0.023) by multivariable analysis. CONCLUSIONS: Determination of VEGF-C expression is important in predicting nodal metastasis and poor clinical outcome in pT2 gastric cancer patients.     

Expression of vascular endothelial growth factor-C and angiogenesis in esophageal squamous cell carcinoma

AIM: To investigate the expression of vascular endothelial growth factor-c (VEGF-C) mRNA and microvessel density (MVD) in human esophageal squamous cell carcinoma (ESCC) and its relationship with clinical significance. METHODS: Specimens obtained from 43 patients undergoing surgical resection for ESCC were used in this study. The expression of VEGF-C mRNA was examined by in situ hybridization. Tumor MVD was determined immunohistochemically with anti-CD31 antibody and estimated by image analysis. Ten sections of adjacent normal mucosa were also examined. RESULTS: VEGF-C mRNA expression was detected in cytoplasm of carcinoma cells. Of the 43 ESCC patients studied, 18 cases (41.9%) were positive for VEGF-C mRNA. No VEGF-C mRNA expression was observed in normal esophageal mucosa. VEGF-C mRNA expression correlated significantly with lymph node metastasis, TNM stage and depth of invasion (P < 0.05). Furthermore, histological grade (differentiation) tended to correlate with VEGF-C mRNA expression, but was not statistically significant (P > 0.05). In tumor lesions, the MVD was significantly greater than that in normal esophageal mucosa. MVD correlated significantly with lymph node metastasis, TNM stage and depth of invasion (P < 0.05), but not with histological grade (differentiation) (P > 0.05). Lesions with VEGF-C mRNA expression had a significantly higher MVD than that of those without VEGF-C mRNA expression (P < 0.05). CONCLUSION: VEGF-C plays a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in ESCC. VEGF-C is one of the important predictors of the biological behavior in ESCC.     

Angiogenic factors stimulate mast-cell migration

Mast cells accumulate at sites of angiogenesis. The factor(s) that control mast-cell recruitment at these sites have yet to be defined. We sought to determine if angiogenic factors result in mast-cell chemotaxis. In this study, we observed that platelet-derived growth factor-AB (PDGF-AB), vascular endothelial cell growth factor (VEGF), and basic fibroblast growth factor (bFGF) each cause directed migration of murine mast cells at picomolar concentrations, with a typical bell- shaped dose-response curve. Another potent angiogenic factor, platelet- derived endothelial cell growth factor (PD-ECGF), appears to promote chemokinesis of mast cells, whereas tumor necrosis factor-alpha, a weak angiogenic factor, is less robust but still functions as a mast cell chemotactic factor. Epidermal growth factor (EGF), a growth factor with minimal angiogenic properties, was ineffective as a mast cell chemotactic factor. A checkerboard analysis confirmed the directional chemotactic response of PDGF-AB, VEGF, and bFGF, while indicating the chemokinetic response induced by PD-ECGF. Cross-desensitization of growth-factor-induced directed migration was observed between PDGF-AB and bFGF, and also between PDGF-AB and PD-ECGF. Tyrosine kinase- inhibitor genistein effectively dampened the chemotactic responses, whereas pertussis toxin had no effect. In summary, our findings suggest that factors known to act on endothelial cells and stimulate neovascularization may simultaneously serve to recruit mast cells to these sites. The local accumulation of mast cells is believed to facilitate new vessel formation through complex cell:cell interactions.     

OPN和VEGF-C在胃癌中的表达及其临床意义

目的:评价骨桥蛋白(osteopontin,OPN)和血管内皮生长因子C(vascular endothelial growth factor C,VEGF-C)在胃癌中表达及与临床病理参数之间相关性,进一步探讨二者的共表达在胃癌淋巴结转移中的机制.方法:收集复旦大学附属中山医院手术切除胃癌组织标本及患者相关临床资料,对纳入研究的93例胃癌原发灶标本采用免疫组织化学染色法(EnVision二步法),检测OPN与VEGF-C蛋白的表达.结果:93例胃癌组织中OPN与VEGF-C的阳性表达率分别为64.5%(60/93)和69.9%(65/93),在非肿瘤性胃黏膜中均未见其阳性表达;OPN和VEGF-C的表达与胃癌浆膜侵犯、TNM分期以及淋巴结转移呈明显相关(P<0.05).蛋白之间的相关性分析显示,OPN与VEGF-C之间存在正相关(r=0.493,P<0.01).结论:联合检测OPN与VEGF-C有助于阐述胃癌发生发展、浸润转移的机制,OPN可能通过上调VEGF-C的表达促进胃癌的淋巴结转移.     

Le VEGF en physiologie et pathologie thyroïdienne

Angiogenesis is a physiological process involving the growth of new vessels from preexisting vasculature. The vascular endothelial growth factor (VEGF) is an important regulator of both benign and malignant disease process in the thyroid gland. The VEGF family includes seven members called respectively VEGF-A, also known as the VPF (vascular permeability factor), VEGF-B, VEGF-C, VEGF-D, all described in mammalians, VEGF-E (found in parapoxviridae), VEGF-F (also called svVEGF, for snake venom VEGF, found in the venom of viper) and PlGF (for placental growth factor). The thyrocytes are able to synthesize and to secrete the VEGF. VEGF-A is implicated in tumour growth and metastasis via blood vessels while VEGF-C and VEGF-D, implicated in lymphangiogenesis, favour metastasis to the cervical lymph nodes during papillary thyroid carcinomas. The importance of VEGF expression could correlate with a poorer outcome in papillary thyroid carcinomas. Because of its important role in malignant angiogenesis, the VEGF is the privileged target of a new variety of therapeutic agents called angiogenesis inhibitors.     

VEGF in physiological process and thyroid disease

Angiogenesis is a physiological process involving the growth of new vessels from pre-existing vasculature. Vascular endothelial growth factor (VEGF) is an important regulator of both benign and malignant disease processes in the thyroid gland. The VEGF family includes seven members respectively named VEGF-A, also known as VPF (vascular permeability factor), VEGF-B, VEGF-C, VEGF-D, all described in mammals, VEGF-E (found in Parapoxviridae), VEGF-F (also called svVEGF, for snake venom VEGF, found in viper venom) and PlGF (placental growth factor). Thyrocytes are able to synthesize and secrete VEGF. VEGF-A is implicated in tumour growth and metastasis via blood vessels while VEGF-C and VEGF-D, involved in lymphangiogenesis, favour metastasis to the cervical lymph nodes in papillary thyroid carcinomas. High levels of VEGF expression in thyroid tumour cells may correlate with a poorer outcome in papillary thyroid carcinomas. Because of its important role in malignant angiogenesis, VEGF is the preferential target of a new variety of therapeutic agents called angiogenesis inhibitors.     

Tissue concentration of platelet-derived endothelial cell growth factor in colorectal cancer

BACKGROUND: Angiogenesis is essential for the continuous growth of tumour cells under unfavourable conditions in patients. Experimentally, platelet-derived endothelial cell growth factor (PD-ECGF) promotes tumour proliferation by stimulating angiogenesis. However, the clinical significance and regulating mechanism of its production in colorectal cancer are not well understood. METHODS: The tissue concentration of PD-ECGF in colorectal neoplasm and normal mucosa was determined. The systemic oxygenation and nutritional status of the patients were also evaluated. RESULTS: The mean concentration of PD-ECGF in the cancer was significantly higher than that in the normal mucosa or adenoma. The tissue concentration of PD-ECGF in the cancer was associated with the clinicopathologic findings, including the tumour size, serosal invasion, lymphatic vessel involvement, and lymph node metastasis. It was also correlated with the patient's age, levels of PO2 and O2 saturation in arterial blood, and the variables reflecting nutritional status. The multivariate regression model showed that the serum concentration of cholinesterase, the arterial level of PO2, lymph node metastasis, and the tumour size were the independent factors that influenced the tissue concentration of PD-ECGF in colorectal cancer. In contrast, these factors were not associated with the PD-ECGF concentration in normal mucosa. CONCLUSIONS: PD-ECGF may play an important role in the progression of colorectal cancer. Systemic deterioration of oxygenation and nutritional condition in wasted patients may also lead to local activation of PD-ECGF specifically in the cancer tissue. PD-ECGF may be indispensable for maintaining relentless growth of colorectal cancer, and the control of its expression may be of therapeutic importance.     

Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma： TP63is amplified in early carcinogenesis but down-regulated as disease progressed

AIM: By using comparative genomic hybridization, gain of 3q was found in 45-86% cases of esophageal squamous cell carcinoma (EC-SCC). Chromosome 3q25.3-qter is the minimal common region with several oncogenes found within this region. However, amplification patterns of these genes in EC-SCC have never been reported. The possible association of copy number changes of these genes with pathologic characteristics is still not clear. METHODS: Real-time quantitative PCR (Q-PCR) was performed to analyze the copy number changes of 13 candidate genes within this region in 60 primary tumors of EC-SCC, and possible association of copy number changes with pathologic characteristics was analyzed by statistics. Immunohistochemistry (IHC) study was also performed on another set of 111 primary tumors of EC-SCC to verify the association between TP63 expression change and lymph node metastasis status. RESULTS: The average copy numbers (±SE) per haploid genome of individual genes in 60 samples were (from centromere to telomere): SSR3: 4.19 (±0.69); CCNL1: 5.24 (±0.67); SMC4L1: 2.01 (±0.16); EVI1: 2.02 (±0.12); hTERC. 5.28 (±0.54); SKIL 2.71 (±0.14); EIF5A2. 1.95 (±0.12); ECT2: 9.18 (±1.68); PIK3CA: 8.13 (±1.17); EIF4G1: 1.07 (±0.05); 557: 3.07 (±0.25); TP63: 2.51 (±0.22); TFRC. 2.42 (±0.19). Four clusters of amplification were found: SSR3 and CCLN1 at 3q25.31; hTERC and SKIL at 3q26.2; ECT2 and PIK3CA at 3q26.31-q26.32; and 55T, TP63 and TFRC at 3q27.3-q29. Patients with lymph node metastasis had significantly lower copy number of TP63 in the primary tumor than those without lymph node metastasis. IHC study on tissue arrays also showed that patients with lymph node metastasis have significantly lower TP63 staining score in the primary tumor than those without lymph node metastasis. CONCLUSION: This study showed that different amplification patterns were seen among different genes within 3q25.3-qter in EC-SCC, and several novel candidate oncogenes (SSR3, SMC4L1, ECT2, and SST) were identified. TP63 is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.     

Distinct regulation of genes by bFGF and VEGF-A in endothelial cells

A finely tuned balance of angiogenic inhibitors and inducers controls the activity of angiogenesis characterized by proliferation, migration and differentiation of endothelial cells. Among many angiogenic factors, basic fibroblast growth factor (bFGF) was first identified to be angiogenic whereas vascular endothelial growth factor A (VEGF-A) is an endothelial cell specific mitogen. In addition to being a specific mitogen, VEGF-A is also known as a vascular permeability factor. The majority of growth factors transduce their mitogenic signals from cell surface to nucleus where gene expression occurs. Whether these ligands utilize a distinct or a common molecular pathway to exert their biological effects on human endothelial cells remains elusive. We thus studied the expression profile of 884 human genes under the influence of either bFGF or VEGF-A alone in the context of human endothelial cells. A total of ninety-four genes were differentially regulated by more than two folds. The expression patterns of 32 genes are similar between the treatment of either factor alone whereas those of the remaining 62 genes are only regulated by one but not the other factor. Their function in the control of angiogenesis will be discussed and apoptotic signaling in the regulation of angiogenesis is also implicated. This revised version was published online in June 2006 with corrections to the Cover Date.     

Platelet-derived endothelial cell growth factor/thymidine phosphorylase concentrations differ in small cell and non-small cell lung cancer.

OBJECTIVE: Platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (TP) has been implicated in cancer angiogenesis, which is critical for tumor growth and metastasis. We investigated the relationship between the tissue concentration of PD-ECGF/TP and the clinicopathologic status in human lung cancer. METHODS: The concentrations of PD-ECGF/TP in the tumor extracts of 139 primary human lung carcinomas were measured by using a highly specific and sensitive enzyme-linked immunosorbent assay. RESULTS: PD-ECGF/TP was detected in the extracts from 137 of 139 specimens at concentrations that ranged from 2.0 to 169.5 U/mg protein. PD-ECGF/TP concentrations in patients with adenocarcinoma (n = 73) and squamous cell carcinoma (n = 49) were (mean +/- SD) 30.7+/-22.9 U/mg protein (range, 7.6 to 169.5 U/mg protein) and 32.0+/-19.8 U/mg protein (range, 8.0 to 84.4 U/mg protein), respectively. No significant difference was found in the PD-ECGF/TP concentration between these two types of non-small cell lung cancer (NSCLC). However, a > 8-fold lower mean concentration of PD-ECGF/TP was found in tissue extracts from small cell lung cancer (SCLC) (n = 17; 3.65+/-2.01 U/mg protein, ranging from undetectable to 6.1 U/mg protein) than in those from adenocarcinomas (p = 0.00005) or squamous cell carcinomas (p < 0.00001). CONCLUSIONS: The striking difference in PD-ECGF/TP concentrations between SCLC and NSCLC suggests that these two types of lung cancer use alternative pathways for angiogenesis. The present study suggests that inhibitors of PD-ECGF/TP, which have been recently developed and are under laboratory investigation to test their effectiveness as treatments for various types of cancer, may not be effective against SCLC.     

Expression of vascular endothelial growth factor-C and the relationship between lymphangiogenesis and lymphatic metastasis in colorectal cancer

AIM: To investigate the expression of vascular endothelial growth factor-C (VEGF-C) and the relationship between VEGF-C and lymphangiogenesis, lymph node metastasis in colorectal cancer. METHODS: Fifty six cases of colorectal cancer were selected randomly. Expression of VEGF-C was detected by immunohistochemistry, and lymphatic vessels were stained by enzyme histochemical method. RESULTS: VEGF-C expression was found in 66.7% (37/56) patients. In VEGF-C positive and negative patients, the lymphatic vessel density was 25.16+/-7.52 and 17.14+/-7.22, respectively (P<0.05). The rate of lymph node metastasis in VEGF-C positive patients (81.1%) was significantly higher than that in the negative group (42.1%). CONCLUSION: VEGF-C expression may induce lymphangiogenesis in colorectal cancer, as a result, tumor cells can entry the lymphatic vessels easily. VEGF-C may serve as a useful prognotic factor in colorectal carcinoma.     

Accelerated lymphangiogenesis in malignant lymphoma: possible role of VEGF-A and VEGF-C

There is little information regarding the lymphangiogenesis of malignant lymphoma. In this study, we evaluated the lymphangiogenesis and angiogenesis in 44 lymph nodes of 39 malignant lymphomas and five non-reactive normal lymph nodes, based on the lymphatic vessel density (LVD) and microvessel density (MVD) calculated by the computer-assisted assessment of vessel density. The LVD of malignant lymphomas was significantly higher than that of non-reactive normal lymph nodes, irrespective of subtypes (P = 0.00077). On the contrary, there was no difference in MVD between malignant lymphomas and non-reactive normal lymph nodes, except for diffuse large B cell lymphomas, which had a significantly low value of MVD, in comparison with non-reactive normal lymph nodes (P = 0.009). We further examined the expression of vascular endothelial growth factor (VEGF)-C and VEGF-A, which function on lymphangiogenesis in lymph node samples. VEGF-C was expressed in 36 of 39 malignant lymphomas. All 39 of the malignant lymphoma samples expressed VEGF-A. Furthermore, the level of LVD and VEGF-A or VEGF-C was positively correlated. These findings suggest that lymphangiogenesis is actively developed in lymph nodes of malignant lymphomas and it may be induced by both VEGF-A and VEGF-C secreted from lymphoma cells.