Vascular endothelial growth factor in nasal polyps: a comparison of asthmatic and non-asthmatic patients

The cause of nasal polyps remains unknown, although there is a well-recognized clinical association between nasal polyposis and asthma. The characteristic histological features of nasal polyps include large quantities of extracellular fluid. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and vascular permeability. This study aimed to compare expression of VEGF in nasal polyps from patients with asthma and those with no apparent respiratory disease. Twenty-four asthmatic and 35 non-asthmatic patients were studied using immunohistochemistry for VEGF. VEGF expression was identified in endothelial, inflammatory and epithelial cells. There was significantly greater endothelial expression of VEGF in asthmatic patients (P < 0.05). Greater epithelial expression was observed in asthmatic patients but this did not reach statistical significance (P = 0.07). There was no difference in the density of inflammatory cells expressing VEGF. Differences between the two groups may reflect differences in disease severity or in the nature of the inflammatory process.     

Activated eosinophils in nasal polyps: a comparison of asthmatic and non‐asthmatic patients

Objectives: There is a recognized clinical association between nasal polyps and asthma. Nasal polyps and the airways of asthmatic patients demonstrate marked eosinophilia suggesting that this inflammatory cell may have a key role to play in both conditions. The objective of this study was to determine whether nasal polyps from patients with asthma had a greater density of activated eosinophils than patients with no associated respiratory disease. Design: Archived specimens were retrieved from patients who had undergone nasal polyp surgery and their case notes reviewed. Activated eosinophils were identified using immunohistochemistry for a monoclonal antibody to secreted eosinophil cationic protein (EG2). Setting: Teaching hospital otolaryngology unit. Participants: Consecutive patients who had undergone nasal polyp surgery in 1994 were recruited. The diagnosis of asthma was based on a documented physician diagnosis and appropriate drug treatment. Twenty‐four asthmatic and 35 non‐asthmatic patients were studied. Main outcome measures: Eosinophil density was measured using a standardized counting technique. Results: Asthmatic patients were significantly more likely to have had previous polyp surgery (chi‐square test: P < 0.05). Areas of intense eosinophilia were identified in all samples. There was a significant greater degree of activated eosinophilia in the asthmatic patients (t‐test: P < 0.05). Conclusions: We have demonstrated a higher number of previous operations in asthmatic patients, and also a greater degree of activated eosinophilia in asthmatic polyps compared with non‐asthmatics. This would suggest that eosinophil activity has a role to play in the pathogenesis of nasal polyps.     

Immunohistochemical demonstration and semi-quantitation of vascular endothelial growth factor in recurrent versus non-recurrent nasal polyps

Objective The expression of some growth factors in nasal polyps has been examined, although investigations addressing the reason for recurrence in some patients are lacking. Vascular endothelial growth factor (VEGF) is expressed by inflammatory cells, as well as by endothelial and epithelial cells of nasal polyps. To determine whether VEGF may play a role in the recurrence of nasal polyps, we aimed to compare VEGF expression in recurrent versus non-recurrent polyps. In addition, expression in polyps from asthmatic patients was compared with that in polyps from non-asthmatics.

Material and Methods A total of 30 patients with newly diagnosed nasal polyposis were included. Polypectomy was performed at enrolment in the long-term follow-up study. Fifteen patients had only 1 polypectomy (non-recurrence group; median observation period 81 months) and 15 had a median of 6.4 polypectomies (multiple recurrence group; median observation period 108 months). Five of 10 patients with asthma belonged to the non-recurrence group and 5 to the recurrence group. The polyp obtained at the initial polypectomy was examined for expression of VEGF by immunohistochemistry, using a polyclonal antibody. A blinded semi-quantitation and comparison of the intensity of immunolabelling were performed in recurrent versus non-recurrent polyps, as well as in asthmatics versus non-asthmatics.

Results VEGF expression was seen as varying staining of the polyp surface and gland epithelium, as well as of the vessel endothelium and some stromal mono- and polymorphonuclear leukocytes. Semi-quantitation of the staining intensity showed no significant differences between recurrent and non-recurrent polyps, or between asthmatics and non-asthmatics.

Conclusion Our findings indicate that the level of immunohistochemical expression of VEGF in recurrent and non-recurrent nasal polyposis is equivalent. Thus, the level of VEGF expression cannot predict a subsequent recurrence. The expression of VEGF is not upregulated in patients with asthma. Further studies are needed to determine the role of VEGF in nasal polyposis, with special reference to different stages of polyp formation, vascularization and growth.     

Immunohistochemical demonstration and semi-quantitation of vascular endothelial growth factor in recurrent versus non-recurrent nasal polyps

OBJECTIVE: The expression of some growth factors in nasal polyps has been examined, although investigations addressing the reason for recurrence in some patients are lacking. Vascular endothelial growth factor (VEGF) is expressed by inflammatory cells, as well as by endothelial and epithelial cells of nasal polyps. To determine whether VEGF may play a role in the recurrence of nasal polyps, we aimed to compare VEGF expression in recurrent versus non-recurrent polyps. In addition, expression in polyps from asthmatic patients was compared with that in polyps from non-asthmatics. MATERIAL AND METHODS: A total of 30 patients with newly diagnosed nasal polyposis were included. Polypectomy was performed at enrolment in the long-term follow-up study. Fifteen patients had only 1 polypectomy (non-recurrence group; median observation period 81 months) and 15 had a median of 6.4 polypectomies (multiple recurrence group; median observation period 108 months). Five of 10 patients with asthma belonged to the non-recurrence group and 5 to the recurrence group. The polyp obtained at the initial polypectomy was examined for expression of VEGF by immunohistochemistry, using a polyclonal antibody. A blinded semi-quantitation and comparison of the intensity of immunolabelling were performed in recurrent versus non-recurrent polyps, as well as in asthmatics versus non-asthmatics. RESULTS: VEGF expression was seen as varying staining of the polyp surface and gland epithelium, as well as of the vessel endothelium and some stromal mono- and polymorphonuclear leukocytes. Semi-quantitation of the staining intensity showed no significant differences between recurrent and non-recurrent polyps, or between asthmatics and non-asthmatics. CONCLUSION: Our findings indicate that the level of immunohistochemical expression of VEGF in recurrent and nonrecurrent nasal polyposis is equivalent. Thus, the level of VEGF expression cannot predict a subsequent recurrence. The expression of VEGF is not upregulated in patients with asthma. Further studies are needed to determine the role of VEGF in nasal polyposis, with special reference to different stages of polyp formation, vascularization and growth.     

Expression, localization, and significance of vascular permeability/vascular endothelial growth factor in nasal polyps

BACKGROUND: The exact etiologic mechanisms leading to the formation of nasal polyps have remained largely obscure. A key phenomenon of this specific type of chronic inflammatory disease in nasal respiratory mucosa is remarkable edema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) plays an important role in inducing angiogenesis and modulating capillary permeability. OBJECTIVE: To study the expression and localization of VPF/ VEGF as a putative key factor in nasal polyp development. METHODS: Specimens of nasal polyps (n = 12) were harvested during endonasal sinus surgery in patients with polypous chronic rhinosinusitis. Specimens of healthy nasal respiratory mucosa (n = 12) served as controls and were obtained from inferior turbinates of patients undergoing surgery for nasal obstruction without signs and symptoms of inflammatory disease. Frozen sections were immunohistochemically stained for VPF/VEGF and quantitatively analyzed, using computer-based image analysis. RESULTS: The expression of VPF/VEGF in specimens of nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. CONCLUSION: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. Conclusion: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps.     

血管内皮生长因子在鼻息肉组织中的表达和意义

目的探讨血管内皮生长因子(vascular endothelial growth factor, VEGF)在鼻息肉组织中的表达及其在鼻息肉发病中的意义。方法将鼻息肉患者分为A、B 组,A组为Ⅱ型1、2期患者,B组为Ⅱ型3期及Ⅲ型患者。另有20例鼻中隔偏曲患者的正常下鼻甲组织作对照组。采用免疫组化SP法检测三组VEGF的表达。结果正常鼻黏膜中VEGF的染色呈弱阳性,而在A、B组鼻息肉组织中VEGF的阳性率明显高于对照组,B组中阳性率和阳性细胞数均高于A组;VEGF在鼻息肉组织中主要定位于基底膜周围的炎性细胞和上皮细胞以及腺体、血管周围和血管壁内皮细胞。结论VEGF通过在鼻息肉组织中过度表达促进息肉组织内的血管增殖和炎性细胞聚积,促进鼻息肉的发生发展。     

EOS与COX-2在阿司匹林三联征患者鼻息肉组织中的表达及意义

目的:探讨嗜酸粒细胞(EOS)的聚集和COX-2在阿司匹林三联征(ST)发病过程中的调控作用。方法:取94例鼻内镜手术患者鼻息肉组织,其中ST患者34例(ST组),慢性鼻窦炎鼻息肉伴哮喘患者30例(ATA组),慢性鼻窦炎鼻息肉患者30例(对照组),应用苏木精-伊红染色及免疫组织化学SP法检测EOS的分布及COX-2的表达,并经统计学分析EOS、COX-2的表达和分布与临床病理和发病机制的关联。结果:EOS在3组患者鼻息肉组织中均大量浸润,EOS计数均数分别为80.02±6.11、76.62±5.22、65.97±4.78,ST组、ATA组分别与对照组比较差异均有统计学意义(均P<0.05),而ST组与ATA组比较差异无统计学意义(P>0.05)。COX-2在鼻息肉组织中主要表达于黏膜下腺体、腺上皮细胞、上皮细胞、血管内皮细胞及间质中的EOS,阳性细胞计数分别为88.13±6.26、89.46±5.97、91.22±4.11,ST组与对照组表达差异有统计学意义(P<0.05);ATA组表达与对照组比较差异无统计学意义(P>0.05);ST组与ATA组比较差异无统计学意义(P>0.05)。结论:EOS浸润程度不同可能是ST患者接触非甾体抗炎药后发生特有临床表现的炎症基础,COX-2在ST患者息肉组织中表达的差异可能与花生四烯酸代谢途径的转换及鼻息肉的形成有关。     

鼻息肉中一氧化氮合酶表达及其意义

目的 :了解鼻息肉 (NP)中一氧化氮合酶 (NOS)的分布特点和活性及其在NP发病中的作用。方法 :用免疫组织化学法检测 30例NP(NP组 )及 2 0例正常鼻黏膜 (正常鼻黏膜组 )中NOS的表达 ,并用分光光度计法检测其活性。结果 :NP组NOS活性为 (4.0 79± 0 .6 5 5 )U/mg蛋白 ,正常鼻黏膜组为 (1.5 2 6± 0 .310 )U/mg蛋白 ,二者间差异有统计学意义 (P <0 .0 1) ;NP组iNOS有大量细胞表达 ,分布在黏膜上皮、腺体和血管内皮细胞以及炎症细胞中 ,与正常鼻黏膜组比较 ,差异有统计学意义 (P <0 .0 1) ;而eNOS也有表达 ,但与正常鼻黏膜组比较 ,差异无统计学意义 ;NP组i NOS表达明显高于eNOS表达 ,其差异有统计学意义 (P <0 .0 1)。结论 :NP主要表达iNOS ,分布在黏膜上皮、腺体和血管内皮细胞以及炎症细胞中 ,其产生的大量一氧化氮在NP的发病过程中可能起着重要的作用     

Hypoxia effects on vascular endothelial growth factor derived epithelial cells of nasal polyps]

OBJECTIVE: To understand the role of nasal mucous epithelial cells to hypoxia in early stage of nasal polyps(NP) formation. METHODS: Epithelial cells of NP and inferior turbinate (IT) were cultured without serum under normal oxygen and hypoxia, and stimulus of inflammatory cytokines. Erythropoietin (EPO) was regarded as hypoxia mark, and expression of vascular endothelial growth factor(VEGF) mRNA and protein derived from epithelial cells were detected respectively by in situ hybridization and ELISA. RESULTS: 1. Under hypoxia, EPO mRNA was expressed intensely in epithelial cells from NP and IT, and there was no significant difference between both of them. This result suggested that EPO might be regarded as a hypoxic mark. 2. The ability of producing VEGF mRNA increased with cytokines stimulation, especially under hypoxia. Protein level of VEGF from epithelial cells of NP and IT increased with cytokines stimulation, especially in hypoxia and was time-dependent. CONCLUSION: Epithelial cells actively produce vast VEGF under hypoxia. The VEGF induced by hypoxia of the mucosa in middle meatus is of importance in the formation of nasal polyps(NP) in early stage, which may be the major cause of NP formation in middle meatus.     

The expression of vascular endothelial growth factor (VEGF) and VEGF‐C in early laryngeal cancer: relationship with radioresistance

The expression of vascular endothelial growth factor (VEGF) and VEGF‐C in early laryngeal cancer: relationship with radioresistance Angiogenesis is essential for tumour growth and invasion. Vascular endothelial growth factor (VEGF) is a prime mediator of tumour angiogenesis. VEGF‐C is a closely related protein that effects lymphatic endothelial cells and may be important in the process of lymphatic metastasis. The purpose of this study was to evaluate the expression of these cytokines in patients with T1 and T2a glottic, squamous cell carcinoma, in comparison with normal epithelial control tissue, to ascertain any association with radioresistance. Twenty‐two tumours treated by radiotherapy (13 radiosensitive, nine radioresistant) and seven normal control tissues were studied. The minimum follow‐up was 2 years after radiotherapy. Expression of VEGF and VEGF‐C was evaluated by immunohistochemistry of formalin‐fixed, paraffin‐embedded biopsy specimens. Analysis was carried out using a quantitative computer image analyser. Both VEGF and VEGF‐C were detectable in tumour and normal control specimens. There was increased expression in tumour specimens of both VEGF (P = 0.03) and VEGF‐C (P < 0.001). In addition, the expression of VEGF‐C was associated with tumours of higher histological grade (P = 0.021). There was, however, no difference in VEGF and VEGF‐C expression between radioresistant and radiosensitive tumours. The expression of VEGF and VEGF‐C is increased in early laryngeal squamous cell carcinoma (SCC). However, measuring the expression of these proteins cannot predict radioresistance in this tumour group.     

囊泡分子免疫病理学改变对鼻内镜术后鼻腔黏膜上皮预后转归的影响

目的:探讨囊泡分子免疫病理学改变对鼻内镜术后鼻腔黏膜上皮预后转归的影响。方法:依EPOS标准选取40例(80侧)慢性鼻窦炎、鼻息肉患者为研究对象,根据术后对囊泡处理方式的不同分为囊泡刮除(右侧)和不刮除(左侧);依据囊泡数量及大小分为轻度组(44侧,单侧术腔囊泡数目≤5个且囊泡直径均≤5mm)及中重度组(36侧,单侧术腔囊泡数目>5个或囊泡数目≤5个而囊泡直径>5mm)。鼻内镜下比较轻度组、中重度组术后鼻黏膜上皮化情况;用苏木精-伊红染色及透射电镜观察囊泡的病理形态学变化;免疫组织化学法比较术后不同时间各组(术后1～3周、6～8周及11～14周)和对照组(下鼻甲黏膜、鼻息肉)转化生长因子β1(TGFβ1)、血管内皮生长因子(VEGF)表达的变化。结果:病理学观察发现,囊泡上皮基膜不连续、间质水肿、炎细胞浸润、病理性腺体增多;超微结构显示,囊泡微管结构出现异常,线粒体减少;分子免疫学结果显示,在术后1～3周、6～8周及鼻息肉组织中TGFβ1的表达明显高于术后11～14周及下鼻甲黏膜组织(P<0.05);术后6～8周及鼻息肉组织囊泡中VEGF的表达明显高于术后1～3周、11～14周及下鼻甲黏膜组织(P<0.05)。中重度组囊泡刮除较不刮除鼻黏膜更快上皮化,与轻度组比较平均时间缩短1.5周(P<0.05),轻度组囊泡刮除和不刮除对术腔黏膜上皮化的影响差异无统计学意义(P>0.05)。结论:囊泡是鼻内镜术后有可能经历的阶段,其出现可能提示是鼻腔黏膜术后对炎症存在的反映,存在病理形态学改变及VEGF、TGFβ1的高表达,VEGF、TGFβ1术后的动态变化可以成为鼻内镜术后鼻腔黏膜预后转归的监测指标之一。术后对中重度囊泡进行清除有利于鼻腔黏膜的恢复和愈合。     

Basic fibroblast growth factor expression in recurrent versus non-recurrent nasal polyposis

Various growth factors are expressed in nasal polyps, and some of these have been suggested to play a role in polyp formation. A potential relation between growth factor expression and polyp recurrence, however, is undetermined. Basic fibroblast growth factor (bFGF) is expressed in mononuclear cells, as well as in endothelial and epithelial surface and gland cells of nasal polyps. To determine whether bFGF may play a role in the recurrence of nasal polyps, the present study aimed at a comparison of bFGF expression in recurrent versus non-recurrent polyps. Further, the expression in polyps from asthmatic patients was compared with that from non-asthmatics. Thirty patients with newly diagnosed nasal polyposis were included. Polypectomy was performed at entry to the long-term follow-up study. Fifteen patients only had one polypectomy (no recurrence group, with a median observation time of 81 months). Fifteen patients had a median of 6.4 polypectomies (multiple recurrence group, with a median observation time of 108 months). Five of nine patients with asthma belonged to the non-recurrence group and four to the recurrence group. The polyp from the entrance polypectomy was examined for expression of bFGF by immunohistochemistry, using a polyclonal antibody. A masked semi-quantification of staining intensity was performed in recurrent versus non-recurrent polyps, as well as in asthmatics versus non-asthmatics. bFGF expression was seen as varying staining of the polyp surface and gland epithelium, as well as of some mononuclear cells and some fibroblast-like cell profiles in the polyp stroma. Vascular endothelium was labeled occasionally. Semi-quantification of the staining intensity showed no significant differences between recurrent and non-recurrent polyps, or between asthmatics and non-asthmatics. We conclude that the level of immunohistochemical expression of bFGF in recurrent and non-recurrent nasal polyposis is equivalent. Thus, the level of bFGF expression in the primary polyp can not predict a subsequent recurrence. The expression of bFGF is not up-regulated in patients with asthma. Further studies are needed to determine a potential role of bFGF in nasal polyposis, with special reference to different stages of polyp formation and growth.     

鼻息肉中诱导型一氧化氮合酶、Bax及Bcl-2的表达及相关性研究

目的:检测鼻息肉组织中诱导型一氧化氮合酶(iNOS)和凋亡相关基因Bax、Bcl-2的表达及相关性。方法:30例鼻息肉组织,应用TUNEL方法检测其凋亡情况;免疫组织化学SABC法检测iNOS及Bax、Bcl-2的表达;western blot方法检测iNOS、Bax、Bcl-2的表达。结果:①TUNEL方法检测凋亡细胞位于鼻息肉表层上皮细胞及腺体上皮细胞,均为弱阳性。②免疫组织化学法检测iNOS、Bax、Bcl-2均表达于鼻息肉组织上皮细胞、腺上皮细胞、血管内皮细胞和浸润的炎性细胞,阳性表达定位于细胞质,其中Bax表达为弱阳性,iNOS、Bcl-2表达为强阳性。③Western blot检测3种蛋白均有表达条带,iNOS、Bal-2条带清晰,Bax条带软弱,差异有统计学意义(P<0.01);iNOS与Bcl-2的灰度值比值呈正相关(r=0.851,P<0.01);iNOS与Bax的灰度值比值呈负相关(r=-0.714,P<0.01)。结论:鼻息肉组织中存在抗凋亡和促凋亡2种蛋白,iNOS抑制细胞凋亡,可能对鼻息肉的发生、发展起重要的促进作用。     

Expression of vascular endothelial growth factor and transforming growth factor-beta 1 in nasal polyps]

OBJECTIVE: To study the expression and significance of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) and transforming growth factor-beta 1(TGF-beta 1) in nasal polyps. METHODS: Expression of VEGF/VPF and TGF-beta 1 in nasal polyps from 34 patients and middle turbinates from 30 patients with deviation of nasal septum was prospectively studied with immunohistochemistry. Tissue sections were observed under optical microscope. RESULTS: (1) The VEGF/VPF positivity in vascular endothelium and in glandular cell was significantly higher in nasal polyps than in middle turbinates (P < 0.01 and P < 0.05, respectively); (2) The TGF-beta 1 positivity in extracellular matrix and in cells in the stroma was significantly higher in nasal polyps than in middle turbinates(P < 0.005); (3) The distribution and shape of TGF-beta 1 expressing cells in nasal polyps were similar to that of eosinophil, their positivities were significantly correlative; (4) The positivity of VEGF/VPF and TGF-beta 1 did not correlate with clinical type in nasal polyps (P > 0.05). CONCLUSION: (1) The VEGF/VPF may play a key role in the formation of heavy edema of nasal polyps; (2) The TGF-beta 1 may contribute to some of the pathologic changes observed in nasal polyps, such as thickening of the epithelial basement membrane and stromal fibrosis; (3) Eosinophils in nasal polyps represent a major source of TGF-beta 1.     

黏附分子及血管内皮生长因子在鼻息肉中的表达

目的 探讨细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）以及血管内皮生长因子（VEGF）在鼻息肉中的表达与意义。方法25例鼻息肉标本和9例下鼻甲黏膜标本，分别行ICAM-1、VCAM-1、VEGF免疫组化染色和HE染色，光镜下观察比较各种分子表达水平。结果 鼻息肉中可见大量嗜酸性粒细胞（EOS）浸润。ICAM-1、VCAM-1和VEGF均可表达于鼻息肉血管内皮、间质及炎症细胞，且在鼻息肉血管内皮、间质及浸润炎症细胞中的表达趋势呈现正相关关系。结论 ICAM-1、VCAM-1可能与EOS等炎症细胞附壁浸润活化过程关系密切，VEGF可能启动并加强这一病理变化。它们的协同作用可能参与了鼻息肉的病理过程。     

New immunohistologic findings on the differential role of cyclooxygenase 1 and cyclooxygenase 2 in nasal polyposis

BACKGROUND: Cyclooxygenase 1 (Cox-1) plays a key role in arachidonic acid metabolism and in the pathophysiology and immunology of nasal polyposis in patients suffering from aspirin intolerance. We hypothesize that Cox-2 also might be relevant in the etiology of nasal polyps of aspirin-tolerant patients by their effects on inflammatory mediators as well as on microvascular permeability. METHODS: Fifty-two surgical specimens were immunohistochemically labeled for Cox-1 and Cox-2. Specimens were taken from chronically inflamed mucosa (n = 19) and from nasal polyps (n = 19) during endonasal sinus surgery. Controls were obtained from healthy nasal respiratory mucosa (n = 14), harvested during turbinate surgery in patients with nasal obstruction without inflammatory disease. Staining intensities were semiquantitatively assessed and statistically analyzed. RESULTS: In chronically inflamed tissue the expression of Cox-1 and Cox-2 was strongly labeled. However, in nasal polyps the staining pattern of Cox-1 was similar, but Cox-2 expression in epithelial cells was significantly less than in inflamed, nonpolypous specimens. CONCLUSION: These data suggest that while Cox-1 is strongly up-regulated, Cox-2 expression is significantly lower in epithelial cells of nasal polyps than in those of chronic sinusitis without polyps. The relevance of this finding has to be discussed with respect to the regulatory function of Cox on the inflammatory reaction in nasal respiratory mucosa and its hypothetical role in alterations of capillary permeability via vascular permeability factor/vascular endothelial growth factor.     

Immunohistochemical expression of VEGF and VEGF receptors in nasal polyps as compared to normal turbinate mucosa

The factors involved in the development of chronic inflammation and edema in nasal polyps remain to be clarified. The expression of vascular endothelial growth factor (VEGF) has been described in plasma cells, suggesting that plasma cells may play a major role in the development of edema in nasal polyps through the production of VEGF. We performed immunohistochemical analysis using specific antibodies to VEGF and to the known VEGF receptors, VEGFR-1 and VEGFR-2, on paraffin sections of human nasal polyps ( n=11) and controls of human mucosa of the normal middle turbinates ( n=6). In normal turbinate mucosa, sporadic immunostaining for VEGF was observed throughout the endothelial cells of the small veins and arteries. VEGFR-1 and VEGFR-2 expression was faint in the healthy turbinates. In nasal polyp tissues, strong immunostaining for VEGF was found in the endothelium of blood vessels and in the infiltrating perivascular inflammatory cells. Fibroblasts also stained for VEGF. Strong immunolabeling to VEGFR-1 was evident in the vascular endothelium, whereas weak to moderate VEGFR-1-staining was generally confined to scattered mononuclear round cells. Mononuclear round cells and the endothelium of capillaries revealed immunoreactivity to VEGFR-2. These findings support a role for VEGF and its receptors, VEGFR-1 and VEGFR-2, in the development and perpetuation of edema and angiogenesis in nasal polyps.     

Vascular endothelial growth factor and children featuring nasal polyps

BACKGROUND: The aim of this study is to explore the expression of vascular endothelial growth factor within nasal polyps, and the implication of such expression as regards the development of nasal polyps amongst children. MATERIAL AND METHODS: Sixty children suffering from chronic rhinosinusitis were enrolled in this study. Amongst them, 30 patients featured rhinosinusitis with associated nasal polyps. A biopsy specimen was taken from the stalk or the base of the nasal polyp for nasal-polyp sufferers, and the ethmoid sinus for study participants who featured no nasal polyps. The primary lesions biopsied were immunohistochemically stained with a specific endothelial-cell marker and also stained for the presence of vascular endothelial growth factor. The specific level of vascular endothelial growth factor and the mean number of blood vessels present in a visual microscopic (biopsied-specimen) field were calculated under light microscopy (x400). RESULTS: The number of vascular endothelial growth factor-expressing cells for the nasal-polyp group and for the sinusitis group was, respectively, 20.8+/-4.0 and 11.5+/-3.4 per visual field. Correspondingly, the mean intra-polyp blood-vessel density for the nasal-polyp group and that for the control group was, respectively, 10.5+/-2.6 and 5.0+/-1.9 per visual field. The mean intra-polyp blood-vessel density and the number of vascular endothelial growth factor-expressing cells proved to be significantly greater amongst individuals from the nasal-polyp group than was the case for their analogs from the sinusitis group (P<0.01, for both). The presence of vascular endothelial growth factor was found to be distributed predominantly within the vascular endothelium and the mast cells of polyp tissue. In addition, the level of vascular endothelial growth-factor expression and the mean blood-vessel count per field correlated significantly for nasal-polyp tissue (P<0.001). Furthermore, the relative size of nasal polyps correlated significantly with the number of (intra-polyp) vascular endothelial-cell growth factor-expressing cells and the mean blood-vessel density (P<0.05, for both). CONCLUSION: The level of expression of vascular endothelial-cell growth factor (VEGF) and the mean blood-vessel density were shown to be significantly greater within nasal polyps than within corresponding sinusitis mucosa. Clinically, the expression of both of these parameters correlated well with the relative size of nasal polyps. Vascular endothelial growth factor participates in the formation of nasal polyps amongst children suffering from chronic rhinosinusitis (CRS).     

Tenascin在鼻息肉组织中的表达及其临床意义

目的：探讨Tenascin(TN)在鼻息肉组织中的表达和分布特征及其在鼻息肉发生中的可能作用。方法：采用免疫组化链霉菌抗生物素蛋白—过氧化物酶(SP)法检测24例鼻息肉标本(鼻息肉组)和15例慢性肥厚性鼻炎下鼻甲标本(下鼻甲组)中TN的表达，并以5例健康者(对照组)下鼻甲黏膜作对照。结果：鼻息肉组和下鼻甲组黏膜上皮细胞及腺上皮细胞均表达TN；鼻息肉组TN的黏膜上皮阳性细胞表达的吸光度值显著高于下鼻甲组(P＜0．01)；鼻息肉组TN的腺上皮阳性细胞表达的吸光度值显著高于下鼻甲组(P＜0．01)；对照组下鼻甲组织中黏膜上皮及腺体几乎检测不到TN的表达；鼻息肉组腺体TN阳性率明显高于下鼻甲组(P＜0．05)。结论：TN在鼻息肉组织中的高表达与鼻息肉的发生、发展相关；TN在鼻腔内的表达细胞是黏膜上皮细胞和浆液性腺上皮细胞。