Lin Yvonne G, Han Liz Y, Kamat Aparna A, Merritt William M, Landen Charles N, Deavers Michael T, Fletcher Mavis S, Urbauer Diana L, Kinch Michael S, Sood Anil K
Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Cancer. 2007 Jan 15;109(2):332-40. doi: 10.1002/cncr.22415.
EphA2 is overexpressed in the majority of ovarian cancers and predicts poor clinical outcome. Based on EphA2's emerging role in angiogenesis, we hypothesized that tumors overexpressing EphA2 demonstrate greater microvessel density (MVD) and matrix metalloproteinase (MMP) expression.
After Institutional Review Board (IRB) approval, 77 invasive epithelial ovarian tumors were analyzed for CD31, EphA2, MMP-2, MMP-9, and MT1-MMP expression.
The median age of the patients was 59 years (range, 34-83). EphA2 was overexpressed in 76% of tumors and was associated with advanced-stage disease (P < .001) and high-grade histology (P = .04). MVD was stratified into high (>12.7 vessels/high-power field [HPF]) versus low (<or=12.7 vessels/HPF) counts. High MVD was significantly associated with advanced stage (P < .001), presence of ascites (P < .001), and suboptimal surgical cytoreduction (P = .01). MMP expression was scored separately in the stromal (percentage of tumors with high expression: MMP-2 = 43%; MMP-9 = 74%; MT1-MMP = 40%) and epithelial (percentage of tumors with high expression: MMP-2 = 52%; MMP-9 = 61%; MT1-MMP = 44%) compartments. Endothelial cell EphA2 overexpression correlated with epithelial MMP-9 (P = .02), whereas EphA2 overexpression in tumor cells was significantly associated with high MVD (P = .002), as well as strong stromal and epithelial MMP-9 (P = .01 and P = .04, respectively), epithelial MMP-2 (P = .006), and epithelial MT1-MMP (P = .01) expression.
EphA2 overexpression in endothelial and ovarian cancer cells was strongly associated with critical factors involved in angiogenesis and invasion. These findings may explain the poor clinical outcome of patients with EphA2 overexpression.
EphA2在大多数卵巢癌中过度表达，并预示着不良的临床结局。基于EphA2在血管生成中日益凸显的作用，我们推测过度表达EphA2的肿瘤具有更高的微血管密度（MVD）和基质金属蛋白酶（MMP）表达。
经机构审查委员会（IRB）批准后，对77例浸润性上皮性卵巢肿瘤进行了CD31、EphA2、MMP-2、MMP-9和MT1-MMP表达分析。
患者的中位年龄为59岁（范围34 - 83岁）。EphA2在76%的肿瘤中过度表达，且与晚期疾病（P <.001）和高级别组织学（P =.04）相关。MVD被分为高（>12.7个血管/高倍视野[HPF]）与低（≤12.7个血管/HPF）计数。高MVD与晚期（P <.001）、腹水的存在（P <.001）和手术细胞减灭不理想（P =.01）显著相关。MMP表达在基质（高表达肿瘤的百分比：MMP-2 = 43%；MMP-9 = 74%；MT1-MMP = 40%）和上皮（高表达肿瘤的百分比：MMP-2 = 52%；MMP-9 = 61%；MT1-MMP = 44%）区域分别评分。内皮细胞EphA2过度表达与上皮MMP-9相关（P =.02），而肿瘤细胞中EphA2过度表达与高MVD（P =.002）以及强烈的基质和上皮MMP-9（分别为P =.01和P =.04）；上皮MMP-2（P =.006）和上皮MT1-MMP（P =.01）表达显著相关。
内皮细胞和卵巢癌细胞中EphA2过度表达与血管生成和侵袭相关的关键因素密切相关。这些发现可能解释了EphA2过度表达患者不良的临床结局。
