Potential markers that complement expression of CA125 in epithelial ovarian cancer

Potential markers that complement expression of CA125 in epithelial ovarian cancer
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DOI:
10.1016/j.ygyno.2005.06.040
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发表时间:
2005-11-01
影响因子:
4.7
通讯作者:
Bast, RC
Bast, RC
中科院分区:
医学2区
文献类型:
--
作者:
Rosen, DG;Wang, L;Bast, RC

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背景资料。当卵巢癌被诊断为1期时,90%的患者可以通过手术和目前可用的化疗来治愈。目前,只有不到25%的病例在这个阶段被诊断出来。为了提高早期发现卵巢癌的比例,已经设计了筛查策略,利用血清CA125水平的上升来触发经阴道超声检查。CA125作为这种筛查策略的初始步骤的一个局限性是,20%的卵巢癌缺乏该抗原的表达。在CA125表达缺失的卵巢癌中检测血清肿瘤标志物,可提高早期发现的敏感性。296例卵巢癌中,65例(22%)CA125表达弱或缺失。将CA125的组织表达与血清CA125水平进行比较。应用组织芯片免疫组织化学染色方法,对CA125低表达或不表达的65例卵巢上皮性癌、卵巢囊腺瘤、低恶性潜能肿瘤、正常卵巢及其他16例正常卵巢组织中10种潜在的血清肿瘤标志物的表达进行了检测。卵巢上皮性癌手术标本CA125低表达或缺失与术前血清CA125低水平相关。在CA125缺失的卵巢癌中,所有标本(100%)均表达人激肽释放酶10(HK10)、人激肽释放酶6(HK6)、骨桥蛋白(OPN)和克拉丁3。在CA125缺失的卵巢癌中,表达DF3(95%)、血管内皮生长因子(VEGF)(81%)、MUCI(62%)、间皮蛋白(MES)(34%)、HE4(32%)和CA19-9(29%)。然而,当考虑到与正常组织的反应性时,MES和HE4显示出最大的特异性。HK10、OPN、DF3和MUCI的表达也存在差异。在组织表达水平上,在CA125低表达或不表达的卵巢癌中,29-100%可以检测到10个潜在的SET-URN标志物。一些标记物在癌症中的表达比在正常器官中更强烈。需要进一步的研究来证明血清中标志物的互补表达。(C)2005年,爱思唯尔公司出版。
Background. When ovarian carcinoma is diagnosed in stage 1, LIP to 90% of patients call be cured with Surgery and currently available chemotherapy. At present, less than 25% of cases are diagnosed at this stage. To increase the fraction of ovarian cancers detected at an early stage, screening strategies have been devised that utilize a rising serum CA 125 level to trigger the performance of transvaginal sonography. One limitation of CA125 as an initial step in such a screening strategy is that LIP to 20% of ovarian cancers lack expression of the antigen. Serum tumor markers that call be detected in ovarian cancers that lack CA 125 expression might improve the sensitivity for early detection.Methods. From 296 ovarian cancers, 65 (22%) were found to have weak or absent CA 125 expression oil immunoperoxidase staining. Tissue expression of CA 125 was compared to serum CA 125 levels. Using immunoperoxidase staining of tissue arrays, we have assessed expression of 10 potential serum tumor markers in file 65 epithelial ovarian cancers with little or no CA 125 expression and ill ovarian cystadenomas, tumors of low malignant potential, normal ovaries, and 16 other normal tissues.Results. Low or absent expression of CA 125 in surgical specimens of epithelial ovarian cancer was associated with low levels of serum CA 125 in pre-operative serum specimens. In ovarian cancers that lacked CA 125, all specimens (100%) expressed human kallikrein 10 (HK10), human kallikrein 6(HK6), osteopontin (OPN), and claudin 3. A smaller fraction of CA 125-deficient ovarian cancers expressed DF3 (95%), vascular-endothelial growth factor(VEGF) (81%), MUCI (62%), mesothelin (MES) (34%), HE4 (32%), and CA19-9 (29%). When reactivity with normal tissues was considered, however, MES and HE4 showed the greatest specificity. Differential expression was also found for HK10, OPN, DF3, and MUCI.Conclusions. At the level of tissue expression, each of 10 potential Set-Urn Markers could be detected in 29- 100% of ovarian cancers that had low or absent expression of CA125. Several markers exhibited more intense expression in cancers than in normal organs. Further investigation is needed to demonstrate complementary expression of markers in serum. (c) 2005 Published by Elsevier Inc.