CAJ | 학술논문

背景血管生成与肿瘤的发生之间有着密切的关系,目前对脉络膜黑色素瘤的发生发展过程与缺氧及血管生成相关因子相互关系的研究尚属少见.目的研究血管生成相关因子缺氧诱导因子1α(HIF-1α)、诱导型一氧化氮合酶(iNOS)、环氧合酶2(COX-2)及血管内皮生长因子(VEGF)在脉络膜黑色素瘤中的表达及其相互之间的关系.方法收集青岛大学医学院附属医院眼科病理室保存的脉络膜黑色素瘤标本44例和眼睑色素痣石蜡标本16例,应用兔抗人HIF-1α、iNOS、COX-2及VEGF多克隆抗体,采用免疫组织化学SP法测定HIF-1α、iNOS、COX-2及VEGF在脉络膜黑色素瘤组织及眼睑色素痣中的表达并进行比较,评价4种蛋白与脉络膜黑色素瘤临床病例特征的关系,并对4种蛋白在脉络膜黑色素瘤中表达的相互关系进行研究.结果脉络膜黑色素瘤组织中VEGF、HIF-1α、iNOS、COX-2的阳性表达率均明显高于眼睑色素痣组织,差异均有统计学意义(x2 =6.580、4.105、8.350、13.240,P＜0.05);VEGF蛋白在较大体积肿瘤中的表达明显高于体积较小的肿瘤,差异有统计学意义(x2=9.389,P＜0.05),但VEGF蛋白在不同病理分型及不同浸润深度肿瘤中的表达差异均无统计学意义(x2=1.186、5.398,P＞0.05)；HIF-1α在脉络膜黑色素组织中的表达与肿瘤体积大小、病理分型有关,差异均有统计学意义(x=8.664、6.622,P＜0.05),但其与肿瘤的浸润深度无关,差异无统计学意义(x2=4.914,P＞0.05)；iNOS蛋白的表达与肿瘤体积大小有关(x2=8.609,P＜0.05),但与病理类型及浸润深度无关,差异均无统计学意义(x2=4.789、4.309,P＞0.05)；COX-2蛋白的表达在不同体积的肿瘤中明显不同,差异有统计学意义(x2=7.320,P＜0.05),而COX-2蛋白在不同病理分型及浸润深度的肿瘤组织中的表达量差异均无统计学意义(x2=2.772、2.103,P＞0.05).HIF-1α、iNOS、COX-2的表达量与VEGF表达均呈显著正相关(r=0.943、1.000、0.986,P＜0.05)；COX-2与iNOS表达量之间、HIF-1α与iNOS表达量间及HIF-1α与COX-2的表达量间均呈明显正相关(r=0.986、0.943、0.986,P＜0.05).结论 HIF-1α、iNOS、COX-2在脉络膜黑色素瘤中表达升高,其表达水平与VEGF相关,提示3种基因对脉络膜黑色素瘤的血管生成均有一定作用,可通过该作用促进肿瘤组织的生长. 揹景血管生成與腫瘤的髮生之間有著密切的關繫,目前對脈絡膜黑色素瘤的髮生髮展過程與缺氧及血管生成相關因子相互關繫的研究尚屬少見.目的研究血管生成相關因子缺氧誘導因子1α(HIF-1α)、誘導型一氧化氮閤酶(iNOS)、環氧閤酶2(COX-2)及血管內皮生長因子(VEGF)在脈絡膜黑色素瘤中的錶達及其相互之間的關繫.方法收集青島大學醫學院附屬醫院眼科病理室保存的脈絡膜黑色素瘤標本44例和眼瞼色素痣石蠟標本16例,應用兔抗人HIF-1α、iNOS、COX-2及VEGF多剋隆抗體,採用免疫組織化學SP法測定HIF-1α、iNOS、COX-2及VEGF在脈絡膜黑色素瘤組織及眼瞼色素痣中的錶達併進行比較,評價4種蛋白與脈絡膜黑色素瘤臨床病例特徵的關繫,併對4種蛋白在脈絡膜黑色素瘤中錶達的相互關繫進行研究.結果脈絡膜黑色素瘤組織中VEGF、HIF-1α、iNOS、COX-2的暘性錶達率均明顯高于眼瞼色素痣組織,差異均有統計學意義(x2 =6.580、4.105、8.350、13.240,P＜0.05);VEGF蛋白在較大體積腫瘤中的錶達明顯高于體積較小的腫瘤,差異有統計學意義(x2=9.389,P＜0.05),但VEGF蛋白在不同病理分型及不同浸潤深度腫瘤中的錶達差異均無統計學意義(x2=1.186、5.398,P＞0.05)；HIF-1α在脈絡膜黑色素組織中的錶達與腫瘤體積大小、病理分型有關,差異均有統計學意義(x=8.664、6.622,P＜0.05),但其與腫瘤的浸潤深度無關,差異無統計學意義(x2=4.914,P＞0.05)；iNOS蛋白的錶達與腫瘤體積大小有關(x2=8.609,P＜0.05),但與病理類型及浸潤深度無關,差異均無統計學意義(x2=4.789、4.309,P＞0.05)；COX-2蛋白的錶達在不同體積的腫瘤中明顯不同,差異有統計學意義(x2=7.320,P＜0.05),而COX-2蛋白在不同病理分型及浸潤深度的腫瘤組織中的錶達量差異均無統計學意義(x2=2.772、2.103,P＞0.05).HIF-1α、iNOS、COX-2的錶達量與VEGF錶達均呈顯著正相關(r=0.943、1.000、0.986,P＜0.05)；COX-2與iNOS錶達量之間、HIF-1α與iNOS錶達量間及HIF-1α與COX-2的錶達量間均呈明顯正相關(r=0.986、0.943、0.986,P＜0.05).結論 HIF-1α、iNOS、COX-2在脈絡膜黑色素瘤中錶達升高,其錶達水平與VEGF相關,提示3種基因對脈絡膜黑色素瘤的血管生成均有一定作用,可通過該作用促進腫瘤組織的生長.
배경 혈관생성여종류적발생지간유착밀절적관계,목전대맥락막흑색소류적발생발전과정여결양급혈관생성상관인자상호관계적연구상속소견.목적 연구혈관생성상관인자결양유도인자1α(HIF-1α)、유도형일양화담합매(iNOS)、배양합매2(COX-2)급혈관내피생장인자(VEGF)재맥락막흑색소류중적표체급기상호지간적관계.방법 수집청도대학의학원부속의원안과병리실보존적맥락막흑색소류표본44례화안검색소지석사표본16례,응용토항인HIF-1α、iNOS、COX-2급VEGF다극륭항체,채용면역조직화학SP법측정HIF-1α、iNOS、COX-2급VEGF재맥락막흑색소류조직급안검색소지중적표체병진행비교,평개4충단백여맥락막흑색소류림상병례특정적관계,병대4충단백재맥락막흑색소류중표체적상호관계진행연구.결과 맥락막흑색소류조직중VEGF、HIF-1α、iNOS、COX-2적양성표체솔균명현고우안검색소지조직,차이균유통계학의의(x2 =6.580、4.105、8.350、13.240,P＜0.05);VEGF단백재교대체적종류중적표체명현고우체적교소적종류,차이유통계학의의(x2=9.389,P＜0.05),단VEGF단백재불동병리분형급불동침윤심도종류중적표체차이균무통계학의의(x2=1.186、5.398,P＞0.05)；HIF-1α재맥락막흑색소조직중적표체여종류체적대소、병리분형유관,차이균유통계학의의(x=8.664、6.622,P＜0.05),단기여종류적침윤심도무관,차이무통계학의의(x2=4.914,P＞0.05)；iNOS단백적표체여종류체적대소유관(x2=8.609,P＜0.05),단여병리류형급침윤심도무관,차이균무통계학의의(x2=4.789、4.309,P＞0.05)；COX-2단백적표체재불동체적적종류중명현불동,차이유통계학의의(x2=7.320,P＜0.05),이COX-2단백재불동병리분형급침윤심도적종류조직중적표체량차이균무통계학의의(x2=2.772、2.103,P＞0.05).HIF-1α、iNOS、COX-2적표체량여VEGF표체균정현저정상관(r=0.943、1.000、0.986,P＜0.05)；COX-2여iNOS표체량지간、HIF-1α여iNOS표체량간급HIF-1α여COX-2적표체량간균정명현정상관(r=0.986、0.943、0.986,P＜0.05).결론 HIF-1α、iNOS、COX-2재맥락막흑색소류중표체승고,기표체수평여VEGF상관,제시3충기인대맥락막흑색소류적혈관생성균유일정작용,가통과해작용촉진종류조직적생장.
Background Angiogenesis is an essential event for the growth and mobility of malignant tumors,but there is little literature about the effects of anoxia and angiogenesis-related factors on angiogenesis in choroidal melanoma.Objective The aim of this study was to investigate the expression of angiogeneic factors such as hypoxia inducible factor-1α(HIF-1α),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),and vascular endothelial growth factor(VEGF)in choroidal melanoma and their clinical significance.Methods The specimens from 44 cases of choroidal melanoma and 16 cases of eyelid nevi identified by pathology were collected.Immunohistochemistry SP was used to examine the expression of HIF-1α,iNOS,COX-2 and VEGF in the samples.The expression of HIF-1 α,iNOS,COX-2 and VEGF in tumors with different sizes,different pathological types and different growth patterns was evaluated.The correlations among these four proteins in tumor growth and development were assessed.Results The expression of HIF-1α,iNOS,COX-2 and VEGF in choroidal melanoma were significantly higher than those in the eyelid nevi group(x2 =6.58,4.105,8.350,13.240,P＜0.05).The expression of VEGF was associated with tumor size(x2 =9.389,P＜0.05),but not associated with pathological types(x2 =1.186,P＞0.05)and infiltration depth(x2 =5.398,P＞ 0.05).The expression of HIF-1α was associated with tumor size(x2=8.664,P＜0.05)and pathological type(x2=6.622,P ＜ 0.05),but not associated with infiltration depth(x2=4.914,P＞0.05).The expression of iNOS was associated with tumor size(x2 =8.609,P＜0.05),but was not associated withpathological type(x2 =4.789,P＞0.05)and infiltration depth(x2 =4.309,P＞0.05).The expression of COX-2 was associated with tumor size(x2 =7.320,P＜0.05),but was not associated with pathological type(x2 =2.772,P＞0.05)and infiltration depth(x2 =2.103,P＞0.05).The expression of HIF-1 α,iNOS,and COX-2 were significantly correlated with the expression of VEGF(r =0.943,1.000,0.986,P ＜ 0.05).The expression of COX-2 was significantly correlated with the expression of iNOS(r =0.986,P＜0.05).The expression of HIF-1 α was significantly associated with the expression of COX-2(r=0.986,P＜O.05).The expression of HIF-1α was significantly associated with the expression of iNOS(r=0.943,P＜0.05).Conclusions The expressions of the HIF-1 α,iNOS,COX-2 and VEGF protein are up-regulated in choroidal melanoma.They may play important roles in the angiogenesis of the choroidal melanoma.Assessment of the expression of HIF-1α,iNOS and COX-2 may be useful for the diagnosis and therapy of choroidal melanoma.