肿瘤抑制基因PTEN在脉络膜黑色素瘤中的表达及意义

目的研究脉络膜黑色素瘤中PTEN蛋白表达及其与脉络膜黑色素瘤局部侵袭转移机制的相关性。设计回顾性病例系列。研究对象36例脉络膜黑色素瘤和2例正常葡萄膜组织。方法对36例脉络膜黑色素瘤进行组织病理学分析,应用免疫组化方法检测肿瘤组织及正常葡萄膜组织中PTEN的表达,并分析其与组织病理学特征以及同肿瘤侵犯巩膜导管与否之间的关系。主要指标病理组织学、免疫组织化学结果。结果36例脉络膜黑色素瘤组织中,肿瘤侵犯巩膜导管15例(41．7％), PTEN阳性表达20例(55．6％);2例正常葡萄膜组织全部阳性。巩膜导管受侵犯组和未受侵犯组阳性表达率分别为33．3％(5/15例)和76．2％(16／21例)(X2=5．143,P=0．026)。结论PTEN蛋白在脉络膜黑色素瘤侵犯巩膜导管时明显降低。推测PTEN基因的正常表达在抑制脉络膜黑色素瘤细胞的聚集黏附过程中具有重要作用。     

凋亡抑制基因survivin在脉络膜黑色素瘤中的表达及意义

目的探讨凋亡抑制基因survivin在脉络膜黑色素瘤中的表达及其临床意义。方法应用免疫组织化学方法检测51例脉络膜黑色素瘤和10例正常脉络膜组织中survivin蛋白表达情况,分析影响survivin表达的病理因素及预后关系。结果Survivin在正常脉络膜组织中呈阴性表达,51例脉络膜黑色素瘤标本中,34例呈阳性表达（66.67%）,脉络膜黑色素瘤组织中survivin的表达显著高于正常组织（P〈0.01）。Survivin阳性表达率与脉络膜黑色素瘤患者肿瘤位置、肿瘤大小无关（P〉0.05）,而与肿瘤细胞类型、是否侵犯巩膜有关（P〈0.05）。结论Survivin在脉络膜黑色素瘤组织中呈阳性高表达,并与预后相关的临床病理指标之间有密切关系,提示survivin在脉络膜黑色素瘤的发生发展中可能起重要作用。     

组织因子在脉络膜黑色素瘤中的表达及意义

目的探讨组织因子（TF）在脉络膜黑色素瘤（CM）细胞株及人CM组织中的表达,为CM的治疗提供新的思路和方法。方法体外培养人CM细胞株（OCM-1）,应用免疫组织化学染色法观察TF在OCM-1中的表达。对人CM眼球标本行免疫组织化学染色检测TF在CM组织中的表达。结果OCM-1细胞中TF蛋白主要表达在细胞质,阳性细胞率为（85．33±5．47）％。CM组织中TF蛋白主要表达在细胞质,少部分表达于CM细胞膜及CM组织内血管内皮细胞的细胞质。CM组织切片中,TF表达阳性细胞率为（41．60±14．17）％,正常人眼脉络膜组织中TF表达阳性细胞率为（5．65±4．26）％,差异有统计学意义（t=5．433,P〈0．01）。CM组织切片阳性细胞积分光密度（IOD）值为33853．67±16445．30,正常人眼脉络膜组织切片平均IOD值为426．43±316．62,差异有统计学意义（t=4．460,P〈0．01）。结论TF在OCM-1细胞及CM组织中呈特异性表达,可作为CM的一个特异性免疫治疗靶点,为CM的治疗提供了新的思路。     

侵袭与转移相关因子在脉络膜黑色素瘤中表达的研究

目的 探讨脉络膜黑色素瘤中侵袭与转移相关因子缝隙连接蛋白43(Cx43)、上皮型钙黏附分子(E-cadherin)、磷脂酰肌醇-3激酶(PI3K)及结缔组织生长因子(CTGF)的表达及意义.方法 实验研究.采用免疫组织化学法检测27例脉络膜黑色素瘤组织及15例色素痣组织中Cx43、E-cadherin、PI3K及CTGF的表达,并与临床病理资料做对照分析,采用x2检验比较各因子表达阳性率的差异.结果 Cx43、E-cadherin、PI3K及CTGF蛋白在脉络膜黑色素瘤中的表达阳性率分别为74.07%(20/27),44.40%(12/27),74.07%(20/27)和66.67%(18/27),在色素痣中的表达阳性率分别为33.33%(5/15),86.67%(13/15),33.33%(5/15)和20.00%(3/15),Cx43、PI3K及CTGF蛋白在脉络膜黑色素瘤中的表达较色素痣增加,差异有统计学意义(x2=5.060,P=0.024;x2=5.060,P=0.024;x2=6.637,P=0.010).E-cadherin蛋白在脉络膜黑色素瘤中的表达较色素痣降低,差异有统计学意义(x2=5.490,P=0.019).Cx43蛋白在不同组织学类型的脉络膜黑色素瘤中表达阳性率不同:梭形细胞型为40%(4/10),混合型88.89%(8/9),类上皮型为100%(8/8),差异有统计学意义(x2=9.874,P=0.007).PI3K蛋白在不同大小的脉络膜黑色素瘤中表达阳性率不同:小肿瘤为42.86%(3/7),中肿瘤为75%(9/12),大肿瘤为100%(8/8),差异有统计学意义(x2=6.357,P=0.042).Cx43、E-cadherin、PI3K及CTGF蛋白在未累及巩膜的脉络膜黑色素瘤中的表达阳性率分别为50.00%(6/12),83.33%(10/12),50.00%(6/12)和41.66%(5/12),在累及巩膜的脉络膜黑色素瘤中的表达阳性率分别为93.33%(14/15),40.00%(6/15),93.33%(14/15)和86.67%(13/15),Cx43、PI3K及CTGF蛋白在脉络膜黑色素瘤中的表达,累及巩膜组较未累及组增加,差异有统计学意义(x2=4.457,P=0.016;x2=4.457,P=0.016;x2=4.218,P=0.019).E-cadherin在脉络膜黑色素瘤中的表达,累及巩膜组较未累及组降低,差异有统计学意义(x2=3.546,P=0.028).结论 Cx43、PI3K、CTGF蛋白的高表达及E-cadherin蛋白的低表达与脉络膜黑色素瘤的浸润和转移可能有一定的关系.

Abstract：

Objective To investigate the expression of factors related to invasion and metastasis in choroidal melanoma and to determine their relationships with malignant features. Methods The expression of Connexin43 ( Cx43 ) , epithelial cadherin ( E-cadherin) , phosphatidylinositol 3-kinase (PI3K) and connective tissue growth factor ( CTGF ) in choroidal melanoma and nevi were detected by immunohistochemistry, and the correlation between these factors and clinicopathological features were analyzed. Results Positive rates of Cx43, E-cadherin , PI3K and CTGF were 74. 07% (20/27) , 44.4%(12/27), 74.07% (20/27) and 66.67% (18/27) in choroidal melanoma tissues, respectively; and 33.33% (5/15), 86.67% (13/15), 33.33% (5/15) and 20.00% (3/15) in the nevi tissues,respectively. There were significant differences in the expression of these markers between the two groups (x2 =5.060, P=0.024; x2 =5.490, P = 0.019; x2 =5.060, P=0.024; x2 =6.637, P=0.010). The expression rates of Cx43 protein were 40% (4/10) , 88. 89% (8/9) and 100% (8/8) in spindle, mixed and epithelioid cell type, respectively. The expression of these data was related to histological type ( x2 =9. 874,P =0. 007). The expression rates of PI3K protein were 42. 86% (3/7) , 75% (9/12) and 100%( 8/8 ) , in small, medium and large tumors, respectively, and their expression were co-related to the tumor size ( x2 = 6. 357,P = 0. 042 ). Positive rates of Cx43, E-cadherin, PI3K and CTGF were 50% (6/12 ) ,83.33% (10/12), 50% (6/12) and 41.66% (5/12), respectively, in choroidal melanoma tissues without sclera invasion and were 93. 33% ( 14/15 ) , 40% ( 6/15 ) , 93. 33% ( 14/15 ) and 86. 67%(13/15), respectively, in choroidal melanoma tissues with violation involved the sclera. There were significant differences of the expression of these markers between the two groups ( x2 =4. 457, P = 0. 016;X2 = 3. 546, P = 0. 028; x2 = 4. 457, P = 0. 016; x2 = 4. 218, P = 0. 019 ) . Conclusion Increased expression of Cx43, PI3K and CTGF and decreased expression of E-cadherin are involved in the processes of invasion and metastasis of choroidal melanoma.     

Survivin及VEGF在脉络膜黑色素瘤的表达及其与血管形成的关系

目的研究脉络膜黑色素瘤（CM）组织中survivin、血管内皮生长因子（VEGF）与微血管密度（MVD）的相关性,探讨survivin的作用机制。方法采用免疫组织化学SP法检测survivin、VEGF在58例CM组织和8例正常脉络膜组织中的表达,利用CD105标记CM组织的新生血管。结果58例CM组织中survivin蛋白表达阳性率为69％,VEGF阳性率为74％,二者在正常脉络膜组织中均不表达。Survivin和VEGF与患者在不同年龄、肿瘤大小、最大基底径、肿瘤生长方式、巩膜壁浸润与否间差异无统计学意义（P〉0．05）,但与CM的巩膜导管侵犯与否间的比较差异有统计学意义（P〈0．05）;survivin、VEGF在CM组织中的表达与否与MVD的比较差异有统计学意义（P〈0．05）;survivin和VEGF在CM组织中的表达密切相关（r：0．522,P〈0．01）。结论Survivin和VEGF在血管生成过程中密切相关,survivin蛋白可作为CM靶向治疗的靶点。     

脉络膜恶性黑色素瘤

脉络膜恶性黑色素瘤广州市第二人民医院眼科李东豪，龚纯慧脉络膜恶性黑色素瘤，占成年人眼内恶性肿瘤的首位，此瘤恶性程度较高，易经血液转移，在临床诊断上易和许多眼底疾病相混淆，因而是眼科临床工作者不容忽视的一个眼病。－、发病情况葡萄膜恶性黑色素瘤的发病率为...     

彩色多普勒在脉络膜黑色素瘤诊断中的应用

目的 探讨彩色多普勒超声检查在脉络膜黑色素瘤鉴别诊断中的价值.方法 对经病理和手术证实的17例脉络膜黑色素瘤的彩色声像图、病理及临床资料进行回顾性对照分析.结果 本组病例临床与病理诊断符合率为100%.根据声像图表现可分为:半球形、蘑菇形和弥漫形,病灶内血供丰富.结论 彩色多普勒显示病变内的血流信号特征对脉络膜黑色素瘤有鉴别诊断价值.     

脉络膜黑色素瘤的治疗

脉络膜黑色素瘤的治疗方法有多种,如定期观察、敷贴放疗、带电粒子照射、局部切除、经瞳孔温热疗法(transpupillarythermotherapy ,TTT)、眼球摘除、眶内容剜除、化疗和免疫疗法等。现在的发展趋势已由光凝疗法转到对小肿瘤应用TTT ,或对中等、较大肿瘤应用TTT联合放射治疗。本文就脉络膜黑色素瘤患者的治疗方法作一概述。     

脉络膜恶性黑色素瘤1例

脉络膜恶性黑色素瘤１例第２５２医院眼科董翠玲患者信××女５０岁病案号９９２０２１９８８年８月因红眼病自行点药７天后，发现左眼上方视物模糊，８９年４月原来模糊区视力消失，曾就诊于外院，诊断＂花眼＂。９０年３月左眼失明２个月来诊，诊断左眼球内肿物，继发性...     

EOG诊断脉络膜黑色素瘤和脉络膜血管瘤

用ＥＯＧ法检查了７例（７眼）脉络膜黑色素瘤和７例（７眼）脉络膜血管瘤，分别与其健眼比较，发现光峰值、Ａｒｄｅｎ比、ｇｌｉｅｎ比均呈统计学意义的降低；而脉络膜黑色素瘤组与脉络膜血管瘤组二组基值相比，前者基值明显低于正常，具有极显著性差异（Ｐ＜０．００１），提示基值下降伴Ａｒｄｅｎ比下降可作为脉络膜黑色素瘤的眼电生理学特征性改变。     

Cavitary choroidal melanoma

CASE REPORT: We report an unusual case of cavitary choroidal melanoma. The results of ultrasonography, magnetic resonance imaging, computed tomography, and immunohistochemical studies are presented for a 38-year-old woman who developed an amelanotic tumor in the posterior choroid. B-scan ultrasonography disclosed intratumoral cavitations. Systemic and extraocular extension studies were negative. Enucleation was performed and histopathologic examination showed a choroidal melanoma of spindle cell type, with intratumoral cavitations lined by flattened tumor cells.COMMENTS: The majority of previous reports of intraocular cavitary tumors describe cavitary ciliary body tumors. Uveal melanoma should be included in the differential diagnosis of choroidal cavitary lesions. As far as we know, this is the second documented clinicopathologic correlation of a cavitary choroidal melanoma.     

Corneal autofluorescence in choroidal melanoma or in choroidal naevus

AIMS: To investigate whether corneal autofluorescence is different in patients with choroidal melanoma or choroidal naevus. METHODS: Corneal autofluorescence was determined by fluorophotometry in both eyes of 32 patients with a unilateral choroidal melanoma, 32 patients with a unilateral choroidal naevus, and 32 age matched healthy controls. The corneal autofluorescence ratio between affected and contralateral eyes of patients or between randomly selected eyes of healthy controls was calculated. RESULTS: Mean corneal autofluorescence ratio of patients with a choroidal melanoma was significantly higher than that of healthy controls (mean ratio: 1.09 (SD 0.15) and 1.00 (0.09), respectively, ANOVA p=0.014), and than that of patients with choroidal naevus (mean ratio 0.96 (0.09), p<0.001). Mean ratios of patients with choroidal naevus and healthy controls were not significantly different (p=0.27). CONCLUSIONS: Corneal autofluorescence ratio of patients with a unilateral choroidal melanoma is increased. This is probably due to an increased flow of glucose through the impaired blood-aqueous barrier in the affected eye, resulting in additional glycation of corneal proteins and hence in increased autofluorescence. The corneal autofluorescence is not increased in patients with a choroidal naevus, because the blood-aqueous barrier is not impaired in the affected eye in these patients. Measurement of corneal autofluorescence is simple, fast, and non-invasive, and might be helpful to distinguish between patients with choroidal melanoma and those with choroidal naevus.     

Gamma-enolase activity in choroidal melanoma

Gamma-enolase is a glycolytic enzyme that is found in high concentration in neural and neuroendocrine tissues. The enzyme has been considered clinically useful as a tumor marker in the evaluation of small-cell undifferentiated malignancies. A preliminary report suggested that gamma-enolase activity may be used in the assessment of the malignant potential of choroidal melanoma. To test this hypothesis and document the distribution of gamma-enolase in the eye, we studied the immunohistochemical activity of gamma-enolase in six eyes from persons with choroidal melanoma. Although no correlation could be found with gamma-enolase activity and tumor size or tumor cell type, the distribution of gamma-enolase in normal retina and optic nerve was described. The areas of greatest immunohistochemical reactivity were the perikaryon of ganglion cells, inner and outer plexiform layers, and the nerve axons of the nerve fiber layer and optic nerve. Gamma-enolase may be a potentially useful marker of retinal and optic nerve glycolysis, and of neuronal function.     

Brachytherapy in choroidal melanoma]

BACKGROUND AND PURPOSE: Brachyterapy in the management of intraocular tumors was introduced in the Department of Ophthalmology in Cracow in the late sixties, soon after it was applied by Stallard. For many years, similar to other oncological centers, we used 60Co and in 1994 we started with 106Ru and at the end of 1997 with 125J. The aim of this paper is to present our experiences with 106Ru and 125J brachytheray in posterior uveal melanoma. MATERIAL AND METHODS: Our studies comprised 164 patients with choroidal melanoma, treated in the years 1995-1997 with 106Ru and 19 patients treated between December 1997 nad April 1998 with 125J plaque brachytherapy. There were 93 women and 90 men, aged 18-86. Tumor thickness was beneath 6 mm in 85 cases, 6-9 mm in 63 and above 9 mm in 35. In 121 eyes anterior margin of the tumor was located in equatorial region or posterior to it, 62 the tumor situated anterior to the equator attached to the ciliary body. The usual dosage was 60-100 Gy to the tumor apex; in 33 eyes transpupillary thermotherapy (TTT) with diode laser was added. The follow-up ranges from 3 months to 3 years after 106Ru plaque brachytherapy and 1-3 months after 125J. RESULTS: Criteria of the treatment efficacy were decrease of tumor thickness at least 10%, increase of its density and vessel obliterations. Among 164 patients treated with 106Ru improvement was achieved in 84 (51.2%) of cases, stabilization in 50 (30.5%) and negative results in 30 (18.3%). Enucleation was performed in 16 (9.7%) cases. Among 19 patients treated with 125J preliminary evaluation indicates positive reaction for treatment in 14 cases. CONCLUSIONS: Our studies confirm the opinion that brachytherapy is a method of choice in the management of many cases of posterior uveal melanoma. There are significant relationships between the results of treatment and the size of tumor and its location. The adequate choice of the kind of radioactive isotope in the plaque is very important.     

Endoresection of choroidal melanoma

AIMS—The results of 52 endoresections for choroidal melanoma are reported.
METHODS—The current technique involves vitrectomy, retinal incision over or peripheral to the tumour, haemostasis by raising intraocular pressure and by moderate hypotensive anaesthesia, choroidal incision around tumour, endoresection with vitrector, endodiathermy to bleeding points and residual tumour, fluid-air exchange to reattach retina, endolaser to achieve retinal adhesion around the coloboma and destroy residual tumour in the sclera, silicone oil injection with removal after 12 weeks, cryotherapy to the sclerotomies, and adjunctive ruthenium plaque radiotherapy in selected cases.
RESULTS—Patients receiving primary endoresection had a mean age of 53 years, a mean largest basal tumour diameter of 8.2 mm, and a mean tumour thickness of 3.9 mm. 40 tumours extended to within 2 disc diameters of the optic disc, with 17 involving disc. Follow up ranged from 40 days to 7 years (median 20 months). At the last visit, 90% of eyes were retained, with vision of 6/6-6/12 (two), 6/18-6/36 (three), 6/60 to counting fingers (18), hand movements (nine), and light perception (four). The main complications were retinal detachment in 16 and cataract in 25. Secondary endoresection (11) was performed after plaque radiotherapy (four), photocoagulation (four), trans-scleral local resection (two), and proton beam radiotherapy (one), with retention of the eye in nine cases. By the close of the study, no patients developed definite local tumour recurrence but one died of metastatic disease 41 months postoperatively.
CONCLUSION—Depending on tumour location, endoresection may conserve central vision or temporal field when radiotherapy would be expected to cause optic neuropathy. Longer follow up is necessary to establish the efficacy of tumour control.

Keywords: uveal melanoma; choroidal melanoma; ocular neoplasms; vitrectomy; endoresection; photocoagulation