Expression of epidermal growth factor receptor: risk factor in uveal melanoma

PURPOSE: To investigate the prognostic significance of the expression of epidermal growth factor receptor (EGFR) in uveal melanoma. EGFR is a transmembrane glycoprotein, and its expression has been correlated with the development of metastases in various malignancies. METHODS: Frozen sections from 22 primary uveal melanomas were examined for EGFR expression by a three-step immunoperoxidase staining, using a mouse anti-human EGFR IgG2b monoclonal antibody. The results were compared with patient survival and clinical and histopathologic parameters. RESULTS: EGFR expression could not be determined on one tumor due to excessive pigmentation. Two patients died of causes unrelated to melanoma, and two patients were lost to follow-up. Out of 21 tumors, six tumors showed immunoreactivity for EGFR. Five of these six patients (83%) died due to metastases, compared with 2 (17%) of 12 patients with no EGFR expression (Kaplan-Meier analysis P = 0.0004). EGFR-positive tumors tended to have a greater tumor prominence and a higher mitotic rate. CONCLUSIONS: The expression of EGFR was significantly correlated with death due to metastatic disease and therefore can be regarded as an important prognostic factor in human uveal melanoma.     

端粒酶在葡萄膜恶性黑色素瘤中的表达及意义

目的 检测端粒酶在人眼葡萄膜黑色素瘤中的表达,探讨其在葡萄膜黑色素瘤发病机制中的作用,为其临床治疗提供新的思路.方法 选取16例因患葡萄膜黑色素瘤而行眼球摘除术的患者,取其葡萄膜黑色素瘤组织,采用PCR-ELISA及PCR-PAGE检测其端粒酶的含量及表达.结果 16例患者中15例的端粒酶检测呈阳性表达,占93.8%.PCR-ELISA结果显示其活性绝大多数呈中度、高度表达,仅1例△A值＜0.15.电泳结果显示为多少不等的梯形条带,其中15例显示为4条以上.结论 葡萄膜黑色素瘤患者端粒酶活性明显增高,可能是肿瘤发生、发展的重要原因之一,抑制端粒酶活性有可能成为葡萄膜黑色素瘤的新型疗法之一.     

Expression of vascular endothelial growth factor in uveal melanoma and its correlation with metastasis

AIMS: To evaluate the expression of vascular endothelial growth factor (VEGF) in uveal melanomas and correlate its presence with tumour characteristics and systemic metastasis. METHODS: 47 cases of ciliochoroidal melanoma enucleated between 1983 and 1993 were retrieved from the pathology archives at the University of Western Ontario. Paraffin sections stained with haematoxylin and eosin, periodic acid Schiff, and periodic acid Schiff without haematoxylin after bleaching of melanin were examined. The expression of VEGF protein was examined by an immunoalkaline phosphatase method following antigen retrieval, using an antibody to VEGF and vector red as the chromogen. The intensity of VEGF immunoreactivity was graded on a scale of 0-7 and correlated with tumour cell type, tumour size, presence or absence of necrosis, pigmentation, mitotic activity, microvascular density, and microvascular pattern. RESULTS: VEGF immunoreactivity was present in 44/47 tumours (94%): the intensity was graded as very weak (1-2) in 29/47 (62%) and as weak or greater in 15/47 (32%). VEGF was also found in the ciliary epithelium, smooth muscle of the ciliary body and iris, retinal ganglion cells, inner photoreceptor segments, and the retinal pigment epithelium. Follow up data were available in 43/47 patients (91.5%), with a median follow up time of 10 years. 16/43 (37%) patients developed metastases. VEGF expression in melanoma was linked to the presence of tumour necrosis and the degree of pigmentation but no statistically significant relation with microvascular pattern, tumour size, or microvascular density was found. There was no statistically significant correlation between VEGF expression and metastasis. CONCLUSIONS: Most ciliochoroidal melanomas express VEGF and expression is correlated with the presence of necrosis but not with the occurrence of systemic metastasis or tumour angiogenesis.     

转化生长因子-β与葡萄膜黑色素瘤

转化生长因子-β(TGF-β)是一种具有多种生物学功能的多肽类生长因子。TGF-β在肿瘤的发生过程中起着双向调节作用,同时TGF-β对细胞的增殖与分化、细胞外基质的产生、血管的生成及机体免疫系统均起着重要作用。近年研究TGF-β的异常过表达以及信号传导通路的异常与葡萄膜黑色素瘤生长和侵袭转移能力密切相关。就TGF-β的结构、功能以及它在葡萄膜黑色素瘤发生过程中的作用进行综述。     

Ultrasonographic tissue characteristics of mushroom-shaped uveal melanoma

PURPOSE: To evaluate the ultrasonographic tissue characteristics of mushroom-shaped versus dome-shaped uveal melanoma and to compare them with the tumor vasculature. METHODS: We examined clinically and ultrasonically 18 dome-shaped and 11 mushroom-shaped uveal melanomas (29 consecutive patients; mean age 57 years) and compared their normalized A-scan patterns.Using histological sections from a different set of patients (12 dome- and 17 mushroom-shaped tumors), we calculated the percentage of area covered by blood vessels. RESULTS: A-scans of dome-shaped tumors presented low homogeneous reflectivity, whereas the heads of mushroom-shaped tumors had high and irregular reflectivity (p < 0.001). The reflectivity of their bases was low and similar to dome-shaped tumors. The blood vessel area in the histological sections was significantly larger in the heads of mushroom-shaped tumors (0.88 +/- 0.14%), compared both to their bases (0.29 i 0.06%) (p < 0.001) and to dome-shaped tumors (0.07 i 0.03%) (p < 0.0001). CONCLUSIONS: The ultrasonographic pattern suggests vascular congestion in the heads of mushroom-shaped tumors,probably due to strangulated blood vessels in the tumor neck.     

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。     

Selected prognostic factors of malignant uveal melanoma

Malignant uveal melanoma is the most common intraocular tumor in adults. Despite very good local treatment results, patients' survival has not improved in the last decades. The main cause of death is metastatic spread, which occurs with a variable time delay after tumor discovery in 50% of patients. After metastasis development the mean survival rate decreases to less than 6 months. Progression to metastatic disease is associated with different prognostic factors. The spectrum of conventional clinical and histopathologic prognostic factors like age, tumor size, location, extrascleral growth, histopathologic cell type, vascularisation, invasion of sclera, etc., has been enlarged by using new immunological, molecular, immunohistochemical and cytogenetical methods. Current research also focuses on development of an adjuvant systemic therapy which could delay or prevent metastasis development in high-risk patients. It is necessary to determine reliable prognostic factors in order to select potential candidates for such a systemic treatment. In this article we present a short overview of known prognostic factors of uveal melanoma.     

Expression of COX-2 and prognostic outcome in uveal melanoma

PURPOSE: The expression of cyclooxygenase-2 (COX-2) and its prognostic value in uveal melanoma was examined. METHODS: Paraffin-embedded sections from 32 clinicopathologically well-characterized cases of primary uveal melanoma were immunohistochemically stained for COX-2. COX-2 expression was evaluated in terms of both the intensity and the extent of staining for each tumor. A COX-2 score encompassing both intensity and extent was also calculated for each specimen. RESULTS: 29 specimens (90.6%) contained moderate or intense positive immunoreactivity for COX-2. A statistically significant association (p<0.05) between COX-2 expression (intensity and score) and metastatic death was established. CONCLUSION: Upregulation of COX-2 expression appears to be associated with poor prognosis in uveal melanoma.     

Expression and distribution of MMPs and TIMPs in human uveal melanoma

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are involved in tumour invasion, metastasis and angiogenesis, and have been implicated as progression markers in uveal melanoma, although their topographical expression has not been fully described. In this study we compared the distribution and specificity of several classes of MMPs (MMP-1, -2, -9, -19, and MT1-MMP) and physiological MMP inhibitors (TIMP-2 and -3) in different regions of the tumour microenvironment and adjacent choroid in a series of primary uveal melanomas. Paraffin sections of untreated uveal melanomas (n=18, 3/18 spindle; 11/18 mixed, and 4/18 epithelioid) were examined for MMP-1 (collagenase 1), MMP-2 and MMP-9 (gelatinases A and B), MT1-MMP (membrane-type 1-MMP), MMP-19, TIMP-2 and TIMP-3 (tissue inhibitors of MMPs), using indirect peroxidase immunohistochemistry. The distribution and intensity of immunolabelling was graded semi-quantitatively (0-3) by 2 independent observers. Non-parametric analyses were used to test for associations between tumour cell type, and the average grade of MMP or TIMP expression. Immunostaining for MMP-1, -9, -19 and MT1-MMP was > or =Grade 2 in more than 70% of specimens, and a heterogeneous pattern of MMP-1, -9, MT1-MMP and TIMP-3 expression was observed. At the tumour-scleral interface (TSI), melanoma cells had a flattened morphology and a much reduced MMP and TIMP expression, with a high expression in tumour areas adjacent to the TSI. Tumour vasculature and stromal cells strongly expressed MMP-2. We also observed heterogeneous immunostaining of the vasculature by MMP-1, -9, MT1-MMP and TIMP-2 antibodies, and of the extravascular matrix by MMP-9 antibody. The distinct immunostaining patterns observed for MMPs and TIMPs within uveal melanoma are consistent with their involvement in tumour growth and angiogenesis. In particular, the heterogeneous expression within regions of the tumours, and the localized expression in vasculature and stromal cells emphasises the importance of the tumour microenvironment in the pathogenesis of uveal melanoma (and other tumours).     

Prognostic factors of liver metastases from uveal melanoma

Objectives This study was designed to assess survival and identify prognostic factors for liver metastases diagnosed by systematic screening in uveal melanoma patients. Methods Among 602 consecutive patients treated over 10 years for uveal melanoma and followed by systematic semi-annual hepatic screening (abdominal ultrasonography), 63 (10.5%) developed liver metastases; these patients form the basis of this study. Factors including patient demographics, characteristics of the uveal tumor, metastasis-free interval, severity of liver metastatic involvement, and treatments of metastases were studied retrospectively regarding their prognostic value, using univariate (Kaplan-Meier method) and multivariate (Cox model) analyses. Results Thirty-five patients (55.6% of the metastatic population) received systemic chemotherapy or best supportive care only; 14 patients (22.2% of the metastatic population) diagnosed with diffuse liver involvement had cytoreductive surgery and intra-arterial chemotherapy; 14 (22.2% of the metastatic population) had complete surgical removal of liver metastases followed by postoperative intra-arterial chemotherapy. No significant surgical complications were experienced. The median overall survival after diagnosis of liver metastases was 15 months. It reached 25 months for selected patients with complete resection (P=0.0002). In this cohort of 63 patients, ten or fewer preoperatively diagnosed metastases and primary uveal melanoma not involving the ciliary body were independently associated with better prognosis. Conclusions This study suggests that selected patients with screened liver metastases from uveal melanoma may benefit from aggressive treatment, including surgery. The two independent favorable prognostic factors are fewer than ten metastases at screening and the absence of ciliary body involvement. Laurent Kodjikian had full access to all the data and takes responsibility for the integrity of the data in the study and the accuracy of the data analysis A summary of this work was presented at the 27th congress of the “Societa Italiana di Chirurgia Oncologica” (May 29–31, 2003) and published as an abstract This work was presented at the 24th Meeting of the Club Jules Gonin, September 2004, Athens (Greece)     

脉络膜黑色素瘤血管生成拟态的三维重建

目的血管生成拟态存在于原发性脉络膜黑色素瘤及其转移瘤中,经体内和体外实验均已证实这些血管生成拟态结构在肿瘤内部与其血循环系统相联系。本研究旨在进一步探求血管生成拟态的三维立体结构,以明确其与肿瘤血管的空间关系。方法原发性脉络膜黑色素瘤标本连续4μm厚切片共25张,层粘连蛋白荧光标记后以共聚焦显微镜观察,每张切片生成系列图像,连续25张切片的系列图像在三维拟真环境中配准叠加,从而获得立体结构重建。结果以层粘连蛋白为主要成分PAS染色阳性的血管生成拟态,二维平面中呈现为环形构成的血管生成拟态,在三维空间显示为薄片管形包绕黑色素瘤细胞聚集成的柱状条索,并形成多数分支和扭转。宿主血管在局部与这些层粘连蛋白阳性标记的柱状管相连。结论血管生成拟态可为造影或诊断提供新的给药途径。     

Using risk factors for detection and prognostication of uveal melanoma

ClinicalDocumented tumor growth has been widely accepted as a risk factor for malignant potential of the lesion.[8,9] Small pigmented lesions that grow have been shown to be malignant melanoma histopathologically.[10] But the growth is not always an indicator of malignancy.[8,11] Choroidal nevi can also show growth, but the amount and rate of growth are generally very little and over a long period of time. On the other hand, some melanomas remain clinically stable, and there have been cases of histopathologically confirmed melanoma that were stable for many years.[12]In 1994, Collaborative Ocular Melanoma Study (COMS) group[13] reported that risk factors for growth and possible malignant transformation were:

• Greater initial tumor thickness and diameter
• Presence of orange pigment
• Absence of drusen, and
• Absence of areas of retinal pigment epithelial changes adjacent to the tumor.

In 1995, Shields et al.[14] statistically derived five risk factors for malignant behavior of small melanocytic choroidal lesions. These features were all based on routine funduscopic examination, making their use practical and significant. They proposed the use of mnemonic TFSOM (To Find Small Ocular Melanoma) to assist the clinician in early detection of small choroidal melanoma at risk for growth and metastasis [Fig. ​[Fig.1d1d–i]. TFSOM stands for:

• T-Thickness greater than 2 mm
• F-Subretinal fluid
• S-Symptoms
• O-Orange pigment present
• M-Margin within 3 mm of the disc.

In their study of 1287 patients,[15] they reported that if none of the above risk factors were present, growth was detected in only 4%. Tumor growth was documented in 30% and 41% of patients with one risk factor, 35% to 58% of patients with 2 risk factors, 36% to 63% of patients with 3 risk factors, and 39% to 62% of patients with 4 risk factors, and 56% of patients with all risk factors. The relative risk (RR) for growth was 1.6-2.3 for 1 factor, 2.8-5.0 for 2 factors, 5.5-9.6 for 3 factors, 11.6-17.3 for 4 factors, and 27.1 for all 5 risk factors combined. The greatest RR for growth occurred when all 5 risks were present, giving 27.1 times greater risk for growth than a tumor with no risk factors [Open in a separate windowRisk factors predicting tumor growth of a suspected small uveal melanoma (Shields et al.)In 2009, Shields et al.[16] after a retrospective analysis of 2514 patients, further modified their mnemonic to include ‘acoustic hollowness’ on ultrasound and “halo” surrounding the tumor. In their study of 408 nevi with ultrasound hollowness, 25% showed growth into melanoma compared to 4% tumors that showed growth “without hollowness.” The COMS also reported low to medium internal reflectivity, often compatible with acoustic hollowness on B scans, in 88% of choroidal melanomas; further strengthening its role in diagnosis.[17] The halo nevus is a pigmented choroidal nevus surrounded by a halo or a circular band of depigmentation. The absence of such a halo around the lesion has been found to be associated with tumor growth (The halo phenomenon can be found with dysplastic nevus and even with melanoma). In their study, the presence of halo suggested nevus stability. The modified mnemonic proposed was “to find small ocular melanoma using helpful hints daily” which stands for:

• LocationJuxtapapillary placed and more anteriorly placed tumors are more likely to be of epitheloid cell and are also more likely to metastasize and progress.[33]PigmentationHeavy pigmentation has been found to be associated with epithelioid cell type and larger sized tumors. Increased pigmentation of the tumor is also associated with necrosis and the presence of macrophages, which increases the risk of malignancy.[33]VascularityA choroidal melanoma shows more prominent vasculature and the vascular prominence is often associated with epitheloid cell type and larger size of the tumor.[33]

  Molecular risk factors

  Micro-metastasis of uveal melanoma is known to occur even prior to primary treatment, which explains substantial rate of metastasis despite treatment.[34] Such metastasis can remain dormant for a prolonged period of time, before becoming clinically detectable.[35] Identifying patients who are at high-risk of harboring undetectable micro-metastases is a challenging but rewarding task. The dissemination of tumor cells into the blood circulation occurs due to lack of lymphatics in the uveal tract. Hematological markers may, therefore, be useful for the detection of distant metastases. This rationale has led for identification of potential molecular markers for the early detection of disseminated tumor cells.

  Tyrosinase m-RNA

  Serum tyrosinase m-RNA levels have been shown to be increased in patients with primary uveal melanoma. Tyrosinase is an enzyme involved in the synthesis of melanin by melanocytes and melanoma cells. Tyrosinase m-RNA can be used for the indirect quantification of circulating tumor cells, and it has been shown that they even correlate with the size of the primary tumor.[36]

  Vascular endothelial growth factor

  Overexpression of vascular endothelial growth factor (VEGF) in melanoma cases is a well-documented fact. It originates from abnormal new vessels within the tumor and hypoxia induced by the irregular blood flow. It is proposed that this overexpression is associated with a proliferative stage of the tumor with metastatic potential.[37,38] Levels of VEGF have been associated with the metastatic potential of uveal melanoma,[39] and serum levels are increased in the presence of micrometastases, and they parallel the extent of liver disease.[38,39]

  Hepatocyte growth factor

  Hepatocyte growth factor and its receptor c-Met have an important role in the growth of cells in the liver. Increased levels of c-Met in uveal melanoma have been shown to be associated with a high risk of metastatic potential.[40]

  Insulin-like growth factor-1

  Insulin-like growth factor-1 (IGF-1) is also produced in the liver. IGF-1 binds to IGF-1R, a surface membrane glycoprotein. Expression of IGF-1R has been associated with a worse prognosis in uveal melanoma.[41] Activation of IGF-1R by binding of circulating IGF-1 increases cell proliferation, prevents apoptosis and is important for integrin adhesion to the extracellular matrix and invasion of basement membranes.[42] Hence in the presence of metastatic disease, serum IGF-1 levels fall.[43] The co-expression of IGF-1 and c-met in uveal melanoma samples is highly predictive of metastasis.[44]Despite the promising role of serum molecular markers in determining metastatic disease at a subclinical level, their application in metastatic surveillance is limited as there is a wide variability in the normal range of values within the population.

  Cytological risk factors

  The advances in treatment for choroidal melanoma have allowed for more and more patients to receive conservative treatment. This has one downside as it precludes obtaining a sample for evaluation of prognostic markers. Naus et al.[45] first reported that fine-needle aspiration biopsy (FNAB) could be reliably used to sample tumors for genetic testing of uveal melanoma. In 2007, Shields et al.[46] demonstrated in 140 consecutive eyes with choroidal melanoma that tissue sample obtained by FNAB immediately before plaque radiotherapy provides adequate DNA for genetic analysis of uveal melanoma using microsatellite assay.

  Chromosomal alterations

  Prescher et al.[47] were the first to describe the chromosome alterations seen specifically in uveal melanoma. The major chromosome alterations have been described in chromosomes 3, 6, 8, and 11.[48] Interestingly, these chromosomal alterations are significantly correlated with the clinical high-risk factors for metastasis in uveal melanoma such as tumor size at diagnosis and epithelioid cell histology.[48] Loss of one copy of chromosome 3 in tumor cell is seen in nearly half of choroidal melanomas and is a risk factor most strongly associated with metastatic death. Monosomy 3 is associated with a 5-year survival of approximately 50%, whereas disomy 3 has been reported to predict 100% survival.[49] Shields et al. in their study on 500 melanoma cases concluded that patients with uveal melanoma demonstrating complete monosomy 3 have substantially poorer prognosis at 3 years than those with partial monosomy 3 or disomy 3.[50]Using gene expression profiling, melanomas have been categorized into two groups:
  • Class I denotes tumors with two copies of chromosome 3 (disomy 3) and other beneficial chromosome changes including gain in chromosome 6p
  • Class II denotes tumors with only one copy of chromosome 3 (monosomy 3) and other deleterious chromosome changes including gain of chromosome 8p and/or isochromosome 8p.
  It is believed that as the tumor undergoes subsequent growth it either, gains a fragment of chromosome 6p and becomes a less aggressive Class I melanoma or it loses a copy of chromosome 3 and develops into a Class II melanoma with high metastatic potential. Class II tumors have a greater chromosomal aneuploidy and a significantly different proliferative capacity as indicated by the expression of Ki-67 antigen.[51] Patients with Class II tumors need increased metastatic surveillance and entry into adjuvant treatment trials.

  Gene alterations

  Mutations in genes GNAQ and GNA11 have been associated with the development of uveal melanoma.[44] GNAQ and GNA11 have overlapping functions in melanocytes, and both genes up-regulate the MAP kinase pathway when constitutively active. Nearly 83.0% of uveal melanomas have been found to have a constitutively active mutation in either GNAQ or GNA11, suggesting that activation of the Gαq–Gα11 pathway is the predominant route to the development of uveal melanoma. GNAQ and GNA11 mutations at codon 209 were encountered in 21.7% and 56.5% of metastatic uveal melanoma samples, respectively.[52] In the same study, GNA11 mutations were more common in locally advanced tumors and tumors of the ciliochoroidal region. In addition, no association was found with chromosome status reinforcing the notion that these mutations are an early pathogenetic event.[53] The various risk factors for metastasis from melanoma are summarized in 相似文献   

葡萄膜黑色素瘤转移相关基因的表达及意义

目的：探讨肿瘤转移相关基因在葡萄膜黑色瘤中的表达及与浸润能力和病理分型的关系。方法：采用免疫组化方法定理检测96例葡萄膜黑色素瘤体标本中EGFR和nm23蛋白的表达,结果：肿瘤的浸润能力与EGFR的表达呈正相关,与nm23的表达则呈负相关,类上皮细胞型,混合细胞型,梭形细胞型EGFR的表达率依次降低,nm23的表达率依次增高,结论：EGFR和nm23是评价葡萄膜黑色素瘤转移潜能的有效指标。     

骨桥蛋白在不同侵袭转移潜能葡萄膜黑色素瘤中的表达及意义

背景 骨桥蛋白(OPN)在多种转移性肿瘤组织中表达增高,但在葡萄膜黑色素瘤(UM)中的表达与临床病理特征及侵袭转移是否相关尚不清楚. 目的 研究UM组织及不同转移潜能人UM细胞系MUM-2B、C918和OCM-1A中OPN的表达情况,分析OPN的组织及细胞系表达水平与UM患者临床病理特征与转移预后之间的关系.方法 收集2004年1月至2007年12月在北京同仁医院行眼球摘除手术并已经病理证实为脉络膜黑色素瘤组织的标本共50例,应用免疫组织化学法检测石蜡标本中OPN的表达,分析其与临床资料的相关性.应用定量聚合酶链反应(Q-PCR)技术检测不同侵袭性转移潜能的人UM细胞系中OPN mRNA的表达情况.结果 50例UM组织中发生肝转移者13例,其中10例OPN表达阳性,未发生肝转移的37例中14例OPN表达阳性;上皮型与非上皮型脉络膜黑色素瘤OPN表达阳性者分别为11/15和13/35;肿瘤累及睫状体和未累及者OPN表达阳性者分别为20/30和4/20;上述指标的比较差异均有统计学意义(X2=5.888、5.510、10.470,P＜0.05).患者不同性别、年龄、眼别、肿瘤最大基底径以及是否侵犯巩膜导管间OPN表达阳性例数的比较差异均无统计学意义(P=0.536、0.256、0.802、0.848、0.555).转移潜能细胞系由高到低依次为MUM-2B、C918、OCM-1A,其OPN mRNA相对表达量分别为1.00±0.04、0.91±0.03、0.08±0.01,差异有统计学意义(F=33.135,P＜0.05),MUM-2B、C918中OPN mRNA的表达水平较OCM-1A中明显增高,差异均有统计学意义(P=0.00),而MUM-2B、C918中OPN mRNA的表达水平差异无统计学意义(P=0.804).结论 OPN与UM侵袭能力及转移潜能密切相关,发生转移的UM组织及高侵袭转移性细胞系中OPN表达水平明显升高,提示OPN可能作为预测UM侵袭能力、转移潜能以及患者预后的指标.