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.     

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.     

The effect of topical corticosteroid on basic fibroblast growth factor in nasal polyp tissue

BACKGROUND: The etiology of nasal polyposis and pathophysiological mechanisms of polyp formation is still poorly understood. Experimental models have suggested that nasal polyp growth requires extracellular matrix formation and is associated with fibroblast proliferation. Intranasal corticosteroids appear to be useful in reducing nasal polypoid lesions and the likelihood of polyp recurrence after surgery. Basic fibroblast growth factor (bFGF) is a potent angiogenesis factor and is mitogenic for a wide range of cell types. We investigated the alteration of bFGF levels in nasal polyp tissue after administration of topical corticosteroid. METHODS: Nasal polyp tissues were obtained from 36 patients with diffuse nasal polyposis before and after topical nasal steroid treatment. As a topical nasal steroid mometasone furoate was given for 4 weeks in a dosage of 200 microg/day. The bFGF levels were measured by competitive enzyme immunoassay method. RESULTS: The mean levels of tissue bFGF, before and after topical nasal steroid treatment, were 1485 +/- 826 ng/mg protein (range, 416-3434 ng/mg) and 1340 +/- 749 ng/mg protein (range, 330-3288 ng/mg), respectively. The levels of bFGF in nasal polyps were significantly lower than those before treatment after administration of topical nasal steroid (p = 0.011). CONCLUSION: Administration of topical nasal steroid decreases bFGF levels of nasal polyp. It may be suggested that one of the effects in diminishing the size of nasal polyps is by decreasing the bFGF.     

Prophylactic budesonide nasal spray after polypectomy

This double blind study compared the effect of budesonide nasal spray with placebo, in the prophylaxis of nasal polyp recurrence after avulsion. 38 cases were given budesonide nasal spray and 25 placebo for 3 months after polypectomy. Follow up of 9 months revealed budesonide treated patients to have significantly lower recurrence rate as compared to the placebo. Interestingly patients with recurrent nasal polyposis benefitted much more from topical budesonide treatment as compared to ones with no previous history of polypectomy.     

Budesonide nasal spray as prophylactic treatment after polypectomy (a double blind clinical trial)

This double-blind parallel-group study compared the effect of budesonide with placebo, in the prophylaxis of nasal polyp recurrence after evulsion. Seventy-three patients with first time or recurrent polypectomy were enrolled. At revisits 3 and 6 months after evulsion, the budesonide-treated patients had significantly lower polyp scores than the placebo-treated patients. Only patients with recurrent nasal polyposis benefited from the budesonide treatment, whereas no effect was evident in patients with first time evulsion.     

Basic fibroblast growth factor in nasal polyps immunohistochemical and quantitative findings

Basic fibroblast growth factor (bFGF) is a mediator with potent mitogenic properties. Increased amounts of this mediator have been demonstrated in damaged lung tissue, and it has been suggested to increase the healing of gastro-duodenal ulcers. In order to quantify the amounts and document the localization of bFGF in nasal polyps, polyp tissue from 12 patients undergoing polypectomy was analyzed by ELISA and immunohistochemistry. Mucosa from the inferior turbinate was analyzed in the same manner for comparison. The amount of bFGF detected in polyp tissue was significantly higher than that in turbinate mucosa. The amount of bFGF was also significantly higher in the group of patients with high degree of inflammation. The immunohistochemical findings demonstrated abundant bFGF activity mainly in the glandular acini, in the epithelium, in infiltrating inflammatory cells and in the vessel walls. We propose that bFGF may contribute in a significant way to the formation of nasal polyps.     

The concentration and expression of IL-5 in human nasal polyp tissue]

OBJECTIVE: To study the concentration and expression of IL-5 in nasal polyp tissues and explore its significance in the micro-environment differentiation of eosinophils accumulation and clarify the conception of nasal polyposis. METHODS: The concentration and expression of IL-5 in nasal polyp tissues of 40 patients were determined by ELISA and immunohistochemistry, and inferior turbinate mucosa from patients with nasal polyps and healthy volunteers was used as control. RESULTS: 1. IL-5 concentration in the polyp tissues was significantly higher than that in inferion turbinate mucosa(P < 0.05). There was no significant difference in inferion turbinate mucosa between the patients with nasal polyps and healthy volunteers (P > 0.05). IL-5 concentration in polyp tissues was markedly higher in patients with extensive polypoid change of nasal mucosa, history of previous polypectomy and allergic rhinitis compared with those without these features (P < 0.05). IL-5 concentration had no correlation with age and sex (P > 0.05). 2. 80.1% of the eosinophils were positive for IL-5 and 90.9% of IL-5 positive cells were eosinophils. Only 3.7% of the lymphocytes and neutrophils were IL-5 positive, and IL-5 was not detectable in epithelial cells. IL-5 expression in eosinophils of polyp tissues was remarkably stronger than that of the turbinate mucosa (P < 0.05). There was no significant difference in inferion turbinate mucosa between the patients with nasal polyps and healthy volunteers (P > 0.05). IL-5 expression of eosinophils in polyp tissues was significantly stronger in patients with extensive polypoid change of nasal mucosa, history of previous polypectomy and allergic rhinitis compared with those without these features (P < 0.05). There was no significant difference in IL-5 expression in lymphocytes and neutrophils between polyp tissues and inferior turbinate nasal mucosa (both P > 0.05). CONCLUSION: IL-5 is a key protein in eosinophilic pathologic mechanisms in nasal polyp tissues.     

Significance and expression of transforming growth factor beta in human nasal polyp tissue]

OBJECTIVE: To explore the pathogenesis of nasal polyposis and the expression of transforming growth factor beta (TGF-beta) in human inflammatory nasal polyps. METHODS: TGF-beta 1-3 in nasal polyp tissues and inferior turbinate mucosa of twenty-five polyposis patients were detected with immunohistochemistry alkaline phosphatase and anti-alkaline phosphatase (APAAP) method. The inferior turbinate mucosa of eight healthy volunteers were selected as control. Six polyp tissues were estimated with double immunolabeling and Western-blot analysis to compare the characterization of the TGF-beta isoforms expression and the proportion of macrophages and eosinophils in nasal polyp tissues. RESULTS: The expression of TGF-beta 1-3 in nasal polyps was significantly higher than that in nasal mucosa and indetecable in nasal mucosa from healthy volunteers; TGF-beta 1 was the main isoform detected in nasal polyps; TGF-beta positively was accompanied by numerous macrophage and eosinophil infiltration. CONCLUSIONS: TGF-beta mainly TGF-beta 1 is strongly expressed in nasal polyps and its mucosa, where it could be produced by macrophages and eosinophils. TGF-beta could induce modification of epithelium and connective tissue and therefore be involved in the pathogenesis of nasal polyposis.     

水通道蛋白-5与鼻息肉手术疗效的相关性

目的观察水通道蛋白-5（aquaporin-5,AQP5）在鼻息肉术后未复发及复发患者鼻息肉组织中的表达及分布,初步探讨AQP5在鼻息肉中的表达程度与鼻息肉手术疗效的相关性。方法选取鼻息肉患者63例,两侧病变以病重侧计,所有病例均在鼻内镜下行鼻息肉摘除及窦口开放术。取63例鼻息肉组织,用4％多聚甲醛固定,石蜡包埋,连续切片,应用HE染色和免疫组织化学技术检测AQP5在未复发和复发鼻息肉组织中的阳性细胞的表达,对AQP5表达程度和手术疗效进行相关性统计学分析。结果AQP5在鼻息肉术后未复发组中的阳性细胞表达显著降低,与复发组比较,差异有统计学意义(P＜0.05)。结论AQP5的高表达可能与术后鼻息肉复发有一定关系;鼻息肉的AQP5的表达程度可以作为预测鼻息肉患者预后指标之一。     

Expression of mammaglobins A and B in nasal polyps is similar in patients with and without allergic rhinitis

BACKGROUND: The causes of nasal polyposis remain unclear. Mammaglobins have been implicated in its pathogenesis. However, their association with the occurrence of nasal polyps in the presence of allergic rhinitis (AR) has not been explored. The aim of this study was to compare the expression levels of mammaglobins A and B with the nasal polyps of patients with and without AR. METHODS: Thirty-one patients with bilateral nasal polyposis underwent skin-prick tests to specific aeroallergens. Nasal polyp tissues were obtained from all patients and divided into two groups as nasal polyps with and without AR depending on clinical history and the skin-prick test results. All polyp tissues were analyzed for the levels of mammaglobin A and mammaglobin B by using real-time quantitative polymerase chain reaction technique. RESULTS: Of the 16 samples from patients having nasal polyps with AR, only 1 sample expressed a detectable level of mammaglobin A (1/16). There was no detectable expression of mammaglobin A in tissues from the group of nasal polyps without AR (0/15). Expression of mammaglobin B was detected in all nasal polyp tissues from both groups. The expression of mammaglobin B was not significantly different between nasal polyps with AR (median, 25th-75th percentiles; 0.023, 0.013-0.046) and nasal polyps without AR (0.032, 0.007-0.16). CONCLUSION: Expression levels of mammaglobins A and B in nasal polyps are not different between patients with and without AR. Our findings suggest that mammaglobins' implication in the pathogenesis of nasal polyps is independent of an underlying AR.     

鼻息肉中血管内皮生长因子和碱性成纤维细胞生长因子的表达

目的探讨血管内皮生长因子 (vascular endothelial growth factor,VEGF)和碱性成纤维细胞生长因子 (basic fibroblast growth factor,bFGF)在鼻息肉发病过程中的意义。方法将鼻息肉患者分为A、B2组,A组为Ⅰ型及Ⅱ型1、2期鼻息肉患者,B组为Ⅱ型3期及Ⅲ型鼻息肉患者,采用免疫组化SP法对2组39例鼻息肉患者鼻息肉组织中VEGF、bFGF的表达进行检测。结果正常鼻粘膜中VEGF、bFGF的染色呈阴性,而在A、B组鼻息肉组织中的阳性率分别达到59%、41%和71%、80%,B组中阳性率和阳性细胞数均高于A组;VEGF和bFGF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血管周围和血管壁内皮细胞。结论 VEGF、bFGF通过在鼻息肉组织中的过度表达,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,可能是鼻息肉病区别于鼻息肉的重要组织学特征之一。     

Expressions of vascular endothelial growth factor and basic fibroblast growth factor in nasal polyp and its role]

OBJECTIVE: To evaluate the role of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor(bFGF) in the pathophysiology of nasal polyp. METHODS: Thirty-nine patients with nasal polyp were divided into two groups: group A(representing type 1 and type 2 phase 1-2) and group B (representing type 2 phase 3 and type 3). The expression of VEGF and and bFGF in both groups were studied with immunohistochemical method. RESULTS: VEGF and bFGF were not detected in norms. The detection rates of VEGF and bFGF were 59%, 41%, and 71%, 80% in group A and group B respectively. The positive rate and the number of positive cells were higher significantly in group B than that in group A. VEGF and bFGF were located mainly in the inflammatory cells and epithelial cells around the basilar membrane and inflammatory cells and endothelial cells around the vessel. CONCLUSIONS: The overexpression of VEGF and bFGF in nasal polyp may contribute to the growth of vessels, accumulation of inflammatory cells, as a result, to enhance the development of nasal polyposis. This phenomenon maybe an important histological mark distinguishing ordinary polyp from polyposis.     

Nasal polyps in children

The inflammatory nasal polyp is the most common benign or malignant nasal mass seen in children. Nasal polyps in the pediatric population appear to occur as inflammatory responses to bacterial infections. In 33% of the patients with polyps whom we studied, antral choanal polyps were noted, and in 20% of the patients the polyps were unilateral but not antral choanal. In 18% of the patients the polyps were bilateral and in an additional 29% they occurred bilaterally in association with cystic fibrosis. History of an allergy is infrequently associated with nasal polyps; allergies are potentially major contributing factors to nasal polyps only in patients without cystic fibrosis whose nasal polyps are bilateral. Patients with antral choanal polyps are most successfully managed by simultaneous Caldwell-Luc antrostomy and polypectomy. Sixty percent of patients with nasal polyps and cystic fibrosis are adequately managed with a single intranasal polypectomy. Simultaneous sinus surgery and polypectomy should be considered for all patients with recurrent polyps and for all patients with clinical or radiographic evidence of significant sinusitis. Complications, including epistaxis and intranasal synechia, occurred in 3% of the 170 surgical procedures performed.     

The effectiveness of steroid treatment in nasal polyposis

OBJECTIVE: The objectives of the management of nasal polyposis are to eliminate or reduce the size of polyps, reestablish nasal breathing, reduce symptoms of rhinitis, restore the sense of smell, and prevent the recurrence of nasal polyps. Local or systemic steroids have been used in the treatment of nasal polyps, but efficacy of combined (local and systemic) steroids in nasal polyposis has been little investigated. The aim of this study was to evaluate the influence of combined steroid therapy on the symptoms and extent of the disease in patients with nasal polyposis. METHODS: Seventeen patients with nasal polyps were treated with combined steroids. Before and after the therapy, polyp size, nasal symptoms, sense of smell, and headache or facial pain were assessed by an established scoring system. RESULTS: After the therapy, symptom scores of all the patients improved. Of the patients, 12% showed a polyp-free nasal cavity, 76% a clear involution of polyps, and 12% no response to the therapy. There were statistically significant differences (P<0.001) for symptom scores and polyp size. Medical ablation of polyps using steroids was not achieved in 88% patients. CONCLUSION: Steroids can reduce polyp sizes and improve the symptoms, but are inadequate to eradicate the polyps. Surgery still plays a major part in the treatment of the nasal polyposis, but steroids can delay the necessity for surgical intervention.     

STAT6在鼻息肉组织中的表达及其与嗜酸粒细胞浸润的关系

目的：研究信号转导和转录激活因子6（STAT6）在鼻息肉组织中的表达及其对嗜酸粒细胞（EOS）浸润聚集的作用,探讨其在鼻息肉发生中的可能作用。方法：选取符合纳入标准的鼻息肉患者手术切除标本（鼻息肉组）30例和同期单纯行鼻中隔偏曲矫正术中切除的下鼻甲组织（对照组）10例。采用免疫组织化学SP法检测2组下鼻甲黏膜中STAT6的表达。应用SPSS13.0软件进行统计学分析。结果：STAT6和EOS在鼻息肉组织中的表达明显高于下鼻甲,差异有统计学意义（P〈0.05）。STAT6阳性细胞主要集中于鼻息肉的上皮细胞、腺体细胞和组织中浸润的炎性细胞的细胞质中。鼻息肉组中STAT6的表达与EOS浸润程度一致（P〈0.01）。结论：STAT6在鼻息肉组织中的高表达及其对EOS浸润聚集的作用,可能与鼻息肉的发生和发展关系密切。     

催乳素在鼻息肉巨噬细胞中的表达及意义

OBJECTIVE: To detect the expression level and distribution of prolactin (PRL) in nasal polyp and to find out the significance of the mechanism of PRL in the invasion of nasal polyp. METHODS: Twenty-five polyp tissues were obtained from the patients who were subjected to nasal polypectomy in our Department. Inferior turbinate mucosa was used as control obtained from 12 patients with rhinogenous snoring. HE staining was performed for routine histopathologic examination. The expression of PRL in nasal polyps was observed by immunohistochemical staining, and six polyp tissues were estimated through double staining for determining cells which expressed PRL. RESULTS: (1) Positive expression of PRL was significantly stronger (t =4.004, P < 0.01) in 25 nasal polyp tissues (2.05 +/- 0.88) than that in 12 normal inferior turbinate mucosa (0.96 +/- 0.50). Positive expression of macrophage (CD68) was significantly stronger (t = 3.519, P < 0.01) in 25 nasal polyp tissues (1.85 +/- 0.83) than that in 12 normal inferior turbinate mucosa (0.93 +/- 0.52). (2) The PRL expressing cell mainly was the macrophage as demonstrated by double immunohistochemical method. CONCLUSION: PRL derived from macrophages of nasal mucosa may participate in the formation of nasal polyp through its local immune modulation.     

No significant role for angiogenesis in nasal polyposis

BACKGROUND: Nasal polyposis is a common disease of which little is currently known. Recent studies have shown up-regulation of several proangiogenic factors. The aim of this study was to assess and quantify how much angiogenesis occurs in nasal polyps and therefore whether angiogenesis is involved in the etiology of polyposis. METHODS: Biopsy specimens of polyp tissue and inferior turbinate (IT) were taken from patients undergoing polypectomy and compared with IT samples from control patients. Five patients were used per study group. Biopsy specimens were either stained with a fluorescent lectin for confocal microscopy or snap frozen and sectioned for histology for the examination of multiple measures of angiogenesis. RESULTS: No significant differences in capillary density, capillary-associated proliferation, capillary surface density, or capillary volume density were seen between the three study groups, and the regression of surface density versus volume density described a linear relationship. Polyp samples showed increases in capillary diameter and interstitial proliferation. CONCLUSION: These results show no active angiogenesis occurring in the polyp or changes in capillary bed architecture, although capillaries seem more edematous in the polyp. As the capillary supply increases in line with the physiological needs of the growing polyp, we conclude that angiogenesis is not a driving force in the etiology of nasal polyposis.     

Flunisolide nasal spray 0.025% in the prophylactic treatment of nasal polyposis after polypectomy. A randomized, double blind, parallel, placebo controlled study

This double blind, parallel study compared flunisolide 2 X 25 mcg in each nostril twice daily, with placebo in the prophylaxis of nasal polyposis recurrence after surgery. The treatment lasted for 12 months. The study was conducted according to the recommendations of the Declaration of Helsinki, and the patients gave verbal consent to participate. The study was reviewed by the Norwegian Medicines Control Authority. Forty-one patients with first or recurrent polypectomy were enrolled. Thirty-seven patients completed the 12 months' period. Four patients dropped out prematurely for reasons unrelated to the test drug. Flunisolide was significantly superior to placebo in preventing recurrence of polyps during 6 to 12 months' treatment, both with respect to number (p = 0.05) and size (p = 0.03) of polyps. Nasal symptoms of sneezing and stuffiness decreased significantly for flunisolide treated patients during treatment. In the placebo group, there was a significant increase in stuffiness throughout the year. For runny nose, there was no difference between the treatments. Six flunisolide patients and 10 placebo patients reported side effects during the one year treatment, transient mild itching being the most common complaint. Three cases of secretion with bloody traces were reported. No patient withdrew for drug related reasons. In this study, flunisolide was significantly more effective than placebo in preventing recurrence of nasal polyposis during one year's treatment after polypectomy.     

鼻息肉中血管内皮生长因子mRNA的检测与意义

目的 :检测鼻息肉组织和鼾症下鼻甲粘膜组织中的血管内皮生长因子 (VEGF) m RN A水平的表达 ,了解其在慢性炎症过程中的作用。方法 :取 6例行下鼻甲切除术的下鼻甲粘膜和 7例鼻息肉切除术的鼻息肉标本 ,用半定量的反转录 -聚合酶链反应 (RT- PCR)方法检测 VEGF的 m RNA表达。结果 :RT- PCR结果显示在鼻息肉组织中 V EGF的表达较鼾症患者下鼻甲粘膜组织明显升高。结论 :鼻息肉组织中 VEGF的表达显著升高 ,推测 VEGF在鼻息肉的形成、生长及复发过程中具有极其重要的作用。