Rosen Daniel G, Wang Lin, Atkinson J Neeley, Yu Yinhua, Lu Karen H, Diamandis Eleftherios P, Hellstrom Ingegerd, Mok Samuel C, Liu Jinsong, Bast Robert C
Department of Pathology, University of Texas M.D. Anderson Cancer Center, Box 355, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Gynecol Oncol. 2005 Nov;99(2):267-77. doi: 10.1016/j.ygyno.2005.06.040. Epub 2005 Aug 2.
When ovarian carcinoma is diagnosed in stage I, up to 90% of patients can 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 CA125 level to trigger the performance of transvaginal sonography. One limitation of CA125 as an initial step in such a screening strategy is that up to 20% of ovarian cancers lack expression of the antigen. Serum tumor markers that can be detected in ovarian cancers that lack CA125 expression might improve the sensitivity for early detection.
From 296 ovarian cancers, 65 (22%) were found to have weak or absent CA125 expression on immunoperoxidase staining. Tissue expression of CA125 was compared to serum CA125 levels. Using immunoperoxidase staining of tissue arrays, we have assessed expression of 10 potential serum tumor markers in the 65 epithelial ovarian cancers with little or no CA125 expression and in ovarian cystadenomas, tumors of low malignant potential, normal ovaries, and 16 other normal tissues.
Low or absent expression of CA125 in surgical specimens of epithelial ovarian cancer was associated with low levels of serum CA125 in pre-operative serum specimens. In ovarian cancers that lacked CA125, all specimens (100%) expressed human kallikrein 10 (HK10), human kallikrein 6 (HK6), osteopontin (OPN), and claudin 3. A smaller fraction of CA125-deficient ovarian cancers expressed DF3 (95%), vascular endothelial growth factor (VEGF) (81%), MUC1 (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 MUC1.
At the level of tissue expression, each of 10 potential serum 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.
当卵巢癌在Ⅰ期被诊断时，高达90%的患者可通过手术及目前可用的化疗治愈。目前，不到25%的病例在此阶段被诊断出来。为了提高早期检测出的卵巢癌比例，已设计出利用血清CA125水平升高来触发经阴道超声检查的筛查策略。CA125作为这种筛查策略的第一步，其一个局限性在于高达20%的卵巢癌缺乏该抗原的表达。在缺乏CA125表达的卵巢癌中可检测到的血清肿瘤标志物可能会提高早期检测的敏感性。
在296例卵巢癌中，65例（22%）在免疫过氧化物酶染色中显示CA125表达较弱或无表达。将CA125的组织表达与血清CA125水平进行比较。通过对组织芯片进行免疫过氧化物酶染色，我们评估了65例CA125表达很少或无表达的上皮性卵巢癌、卵巢囊腺瘤、低恶性潜能肿瘤、正常卵巢以及16种其他正常组织中10种潜在血清肿瘤标志物的表达情况。
上皮性卵巢癌手术标本中CA125表达低或无表达与术前血清标本中血清CA125水平低相关。在缺乏CA125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）和紧密连接蛋白3。一小部分缺乏CA125的卵巢癌表达DF3（95%）、血管内皮生长因子（VEGF）（81%）、MUC1（62%）、间皮素（MES）（34%）、人附睾蛋白4（HE4）（32%）和CA19-9（29%）。然而，当考虑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MUC1也存在差异表达。
在组织表达水平上，10种潜在血清标志物中的每一种都能在29% - 100%的CA125表达低或无表达的卵巢癌中检测到。几种标志物在癌组织中的表达比在正常器官中更强烈。需要进一步研究以证明这些标志物在血清中的互补表达情况。
